bims-simsho Biomed News
on Systems immunology and sex hormones
Issue of 2026–02–22
fifty-four papers selected by
Chun-Chi Chang, Lunds universitet
  1. Sex Differences in Lung Immunity.
  2. Male-biased Cyp17a2 orchestrates antiviral sexual dimorphism in fish via STING stabilization and viral protein degradation.
  3. How Does Biological Sex Impact Mucosal Bacterial Infection? Mucosal Defenses and Bacterial Detection.
  4. Sex-Specific Factors Influencing HIV Infection.
  5. Sex and Ventricular Remodeling.
  6. Androgen receptor modulation of vocal circuitry in Alston's singing mouse.
  7. Sex-Specific Differences in Liver DNA Methylation Patterns and Epigenetic Aging in Mice.
  8. Treatment with a selective androgen receptor modulator (RAD140) is linked to better cardiac function, with male-specific effects that are graded by interleukin-6.
  9. Sex differences in immune modulation: implications for infection, inflammation, and nutritional supplementation.
  10. Maternal gut microbiota mediates prenatal stress-induced fetal blood‒brain barrier dysfunction.
  11. Sex chromosome-dependent epigenetic regulation underlies sex-specific H4 acetylation at the aromatase promoter in the developing mouse amygdala.
  12. The effect of gender-affirming hormonal treatment on personality traits - a NEO-PI-R study.
  13. Review on 11-Oxygenated steroids in hormone-related diseases: polycystic ovary syndrome, endometrial cancer, prostate cancer.
  14. Escape from X inactivation varies across genes and tissues and shapes sex-biased sex chromosome gene expression.
  15. Association of Serum Estradiol and Testosterone With Hip Fractures in Elderly Men.
  16. Not just neurons: Glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.
  17. Mouse strain and sex differences in the number and distribution of salivary gland IgA plasma cells.
  18. Chronic airway inflammation is associated with sex-dependent changes in behaviour, neuroinflammation and the gut microbiome.
  19. Dual Role of the Endometrial Microbiome-Immune Axis: From Endometrial Homeostasis to Reproductive Disorders.
  20. Sexual dimorphism in the cell number of the adult Drosophila brain.
  21. Hormonal transitions across the lifespan shape susceptibility to Sjogren's disease.
  22. Redefining Cardiovascular Medicine: The Journey From "Does Sex Matter?" to "How Does Sex Matter?"
  23. Comparison of intra-ovarian metabolic environment between women with or without PCOS undergoing in vitro fertilization.
  24. Harnessing mucosal immunity for protective vaccines.
  25. B cells and iBALT in TB immunity & pathogenesis.
  26. Endogenous sex hormones, sex hormone-binding globulin, and muscle health: insights into sarcopenia and sarcopenic obesity from the Women's Health Initiative.
  27. Monocyte-derived IL-10 drives sex differences in pain duration.
  28. Bacterial microbiome analysis of vaginal, cervical, and endometrial samples in patients with adenomyosis during the window of implantation.
  29. Intestinal dysbiosis-related infertility: Effectiveness of probiotics and synbiotics supplementation.
  30. Metabolomic profiling of follicular fluid reveals unique pathways in endometriosis and infertility etiologies: a pilot study.
  31. Conserved CD4+ T cell staphylococcal and streptococcal epitopes enable broad-acting vaccines in mice.
  32. Differences in testosterone levels in perianal diseases: A comparative study of abscesses and fistulas.
  33. Impact of maternal visceral leishmaniasis on sex-specific immune responses and pathogenesis in offspring following homologous infections.
  34. Androgen Receptor Signaling Inhibitors for Metastatic Hormone Sensitive Prostate Cancer in Asians: Indirect Comparison.
  35. Pregnancy- and age-associated variation in serum dehydroepiandrosterone concentrations in black and white rhinoceroses.
  36. The human reproductive tract microbiome: A novel source of live biotherapeutics.
  37. A Vaginal Microbiota-Ovary Axis in Chemotherapy-Accelerated Ovarian Aging: Single-Cell Insights into Cellular Dysregulation.
  38. Sticky memories of an activated macrophage.
  39. Alternative splicing and differential gene expression during changes in endometrial receptivity in patients with recurrent implantation failure.
  40. Sex differences in the longitudinal association between metabolomic biomarkers and carotid artery plaques.
  41. Impact of Pre-treatment Testosterone Levels on Severity of Adverse Effects in Men on Androgen Deprivation Therapy for Prostate Cancer.
  42. Sex-specific differences in abscopal responses to combined radiotherapy and immune checkpoint inhibition-insights from a multicenter study.
  43. Decoupling of maternal and neonatal inflammatory levels at the maternal-fetal interface: evidence from a population-based proteomic study.
  44. Menopause, Female Sex Hormones, Skeletal Muscle Mass and Muscle Protein Turnover in Humans.
  45. Age-related mitochondrial energy metabolism reprogramming occurs in granulosa cells during ovarian aging.
  46. Age- and sex-specific reference intervals for 11-oxygenated androgens from infancy throughout childhood and adulthood.
  47. Androgen dysregulates the follicular extracellular matrix and increases pro-fibrotic gene expression in the mouse ovary.
  48. Uterine epithelial estrogen receptor α temporally regulates preimplantation uterine immunity involving interleukin-1β signaling.
  49. Hormonal changes, stable attention: Gender-affirming hormone treatment does not alter selective attention to infant cues in transgender individuals.
  50. Fetal sex-specific differences in the placental transcriptome of gestational diabetes.
  51. Selective estrogen receptor modifiers on the antidepressant-like effects of electroconvulsive seizures in adolescent rats.
  52. Gut microbiota as a key regulator in endometriosis: mechanisms, therapeutic opportunities, and future perspectives.
  53. Correlation of blood lipid levels with the severity of polycystic ovary syndrome and its predictive value for pregnancy outcome.
  54. Sex-specific effects of fecal microbiota transplantation on TBI-exacerbated Alzheimer's disease pathology in mice.
  1. Immunol Rev. 2026 Mar;338(1): e70102
    Sex Differences in Lung Immunity.
    Franz Puttur, Clare M Lloyd.
      Biological sex has a significant impact on how the immune system develops and responds to foreign and self-antigens. Sex differences exist in innate and adaptive immune cells, both at homeostasis and in the context of infection and inflammatory diseases such as asthma, cancer, and autoimmune disorders. Women generate stronger immune responses and are more susceptible to developing autoimmune conditions, while males are more prone to acute viral infections and developing certain cancers. Some immunological differences persist throughout life, while others emerge only after puberty and before reproductive senescence. Additionally, environmental exposures can affect the influence of biological sex in regulating immune function. This is particularly pertinent at mucosal surfaces such as the lungs, where lung immune defenses are constantly exposed to foreign material during respiration. Consequently, environmental factors together with genetics, age and sex hormones play a vital role in governing lung tissue immune responses between the sexes. In this context, we highlight studies that support the need for considering sex as an important biological variable in lung immunological research. This knowledge will provide a benchmark for understanding sex-driven immunological mechanisms that underpin disease development and may inform new avenues targeted for generating sex-specific therapies in lung disease.
    Keywords:  aging; allergy; biological sex; inflammation; lung; processes; sex hormones; tissues
    DOI:  https://doi.org/10.1111/imr.70102
  2. Elife. 2026 Feb 18. pii: RP108048. [Epub ahead of print]14
    Male-biased Cyp17a2 orchestrates antiviral sexual dimorphism in fish via STING stabilization and viral protein degradation.
    Long-Feng Lu, Bao-Jie Cui, Sheng-Chi Shi, Yang-Yang Wang, Can Zhang, Xiao Xu, Meng-Ze Tian, Zhen-Qi Li, Na Xu, Zhuo-Cong Li, Dan-Dan Chen, Li Zhou, Gang Zhai, Zhan Yin, Shun Li.
      Differences in immunity between males and females in living organisms are generally thought to be due to sex hormones and sex chromosomes, and it is often assumed that males have a weaker immune response. Here, we report that in fish, males exhibit stronger antiviral immune responses, the male-biased gene cyp17a2 as a critical mediator of this enhanced response. First, we observed that male zebrafish exhibit enhanced antiviral resistance compared to females, and notably, zebrafish lack sex chromosomes. Through transcriptomic screening, we found that cyp17a2 was specifically highly expressed in male fish. Cyp17a2 knockout males were equivalent to wild-type males in terms of sex organs and androgen secretion, but the ability to upregulate IFN as well as antiviral resistance was greatly reduced. Then, Cyp17a2 is identified as a positive IFN regulator which is located at the endoplasmic reticulum and specifically interacts with and enhances STING-mediated antiviral responses. Mechanistically, Cyp17a2 stabilizes STING expression by recruiting the E3 ubiquitin ligase bloodthirsty-related gene family member 32 (btr32), which facilitates K33-linked polyubiquitination. The capacity of IFN induction of Cyp17a2 was abolished when STING was knocked down. Meanwhile, Cyp17a2 also attenuates viral infection directly to strengthen the antiviral capacity. As an antiviral protein, Cyp17a2 degrades the spring viremia of carp virus (SVCV) P protein by utilizing USP8 to reduce its K33-linked polyubiquitination. These findings reveal a sex-based regulatory mechanism in teleost antiviral immunity, broadening our understanding of sexual dimorphism in immune responses beyond the conventional roles of sex chromosomes and hormones.
    Keywords:  Cyp17a2; STING; TRIM11; cell biology; immunology; inflammation; interferon; ubiquitination; zebrafish
    DOI:  https://doi.org/10.7554/eLife.108048
  3. Immunol Rev. 2026 Mar;338(1): e70112
    How Does Biological Sex Impact Mucosal Bacterial Infection? Mucosal Defenses and Bacterial Detection.
    Laura Ramirez Finn, Molly A Ingersoll.
      Urinary tract infections possess substantial sex disparities in the incidence, immune response, and progression of infection. Some of these distinctions may be due to sexual dimorphism in mucosal barriers or sex differences in the initial immune response to infection. Mucosal organs are protected by a mucus barrier, however, there is little knowledge of the impact of biological sex on this layer in homeostasis and infection. Notably, despite the incidence of infection, there is a paucity of even fundamental research on bladder mucus in homeostasis and infectious disease. When bacteria encounter mucosal epithelia, they must bind and potentially invade these surfaces to initiate an infection. Whether differences in mucosal epithelia have an impact on bacterial-epithelial interactions between the sexes is not known. When bacteria are sensed by the host, they initiate transcription factor activation, which may differ by sex of the host. Finally, sex steroid hormone receptor signaling likely also impacts innate immunity between the sexes, leading to the divergence between the sexes observed in mucosa infection.
    Keywords:  bacterial infections; early immune detection; epithelial invasion; mucus; sex differences
    DOI:  https://doi.org/10.1111/imr.70112
  4. Immunol Rev. 2026 Mar;338(1): e70109
    Sex-Specific Factors Influencing HIV Infection.
    Maria Pujantell, Marcus Altfeld.
      Immune responses are key in controlling viral infections such as HIV-1, which remains a global challenge to public health. X/Y-chromosome-encoded genes and sex steroid hormones can modulate immune cells and drive distinct patterns of gene and protein expression involved in antiviral function, impacting sex-dependent immune responses and altering the balance of specific immune pathways. These sex-specific differences in antiviral immune responses have significant consequences for the outcome of HIV-1 infection. A better understanding of sex differences in HIV-1-specific antiviral immunity is required to implement and develop new strategies for prevention, treatment and ultimately a functional cure against HIV-1. Here we review the impact of X- and Y-encoded genes and the role of sex steroid hormones on modulating antiviral immune responses against HIV-1 and the consequences for disease manifestations in people living with HIV-1.
    Keywords:  HIV‐1; IFN pathway; RNA sensing pathway; TNF pathway; X‐chromosome; escape from XCI; immunity; sex differences
    DOI:  https://doi.org/10.1111/imr.70109
  5. Curr Opin Physiol. 2026 Mar;pii: 100895. [Epub ahead of print]47
    Sex and Ventricular Remodeling.
    Steven P Jones, Helen E Collins.
      The composite of changes sustained by the left ventricle during pathologic and physiologic stimuli is known as ventricular remodeling. These changes involve alterations to individual cells, the surrounding matrix, and overall ventricular structure and function. Following myocardial infarction, ventricular remodeling involves partial tissue repair and ultimately determines long-term survival. Biological sex contributes to diverging responses in post-infarction ventricular remodeling and survival, with young female animals having less remodeling post-injury compared with male animals, yet women have reduced long-term survival. Over the last two decades, evidence indicates that sex-dependent differences impact most processes that contribute to post-infarction remodeling, including extracellular matrix remodeling, inflammation, and cardiomyocyte homeostasis. In addition, there are differences in the transcriptional landscape and cellular composition of male and female hearts. Despite these well-established sex-dependent differences, mechanistic advancements lag. Furthermore, cardiovascular treatments are not yet optimized based on sex. Sex hormones are proffered as the explanation for differences; however, studies that remove the influence of sex hormones still show sex-dependent changes, which suggests hormone-independent contributors. Outside of pathological remodeling in response to infarction, the female heart often undergoes physiological remodeling that does not occur in males: pregnancy. During pregnancy, rapid remodeling and reversion occur, which creates a unique, natural template to study aspects of sex-dependent differences in ventricular remodeling. Therefore, this review summarizes fundamental differences in the ventricular myocardium between sexes and highlights emerging areas that contribute to sex-dependent changes in ventricular remodeling.
    Keywords:  Cardiac Plasticity; Extracellular Matrix; Heart Failure; Inflammation; Sex Hormones
    DOI:  https://doi.org/10.1016/j.cophys.2025.100895
  6. Horm Behav. 2026 Feb 13. pii: S0018-506X(26)00015-2. [Epub ahead of print]179 105890
    Androgen receptor modulation of vocal circuitry in Alston's singing mouse.
    Da-Jiang Zheng, Britt Mardis, Denise Lam, Tarik Islam, Joel Tripp, Steven Phelps.
      Animal advertisement displays are dramatic, often sexually dimorphic behaviors that function in both courtship and competition, and require the coordinated modulation of diverse motivational and motor circuits. In Alston's singing mice, Scotinomys teguina, a novel and elaborate advertisement vocalization is sexually dimorphic and steroid sensitive. Males sing more often than females, and on average male songs have more notes. Song is influenced by circulating androgens, but how such hormonal differences influence the diverse brain regions involved in vocal display is not understood. To characterize androgen-sensitive sites in the vocal pathway, we used two isoforms of pseudorabies virus (PRV) to double-label circuits ending in laryngeal and jaw muscles involved in vocalization, and co-labeled these neurons for androgen receptor (AR). Next, we manipulated circulating androgens and observed the effects on AR distribution and male song. We find androgens drive coordinated changes in AR abundance across motor and motivational circuits, and group differences in song are associated with AR abundance. The results reveal how circulating androgens can coordinate the diverse circuits necessary for elaborate advertisement displays.
    Keywords:  Androgen receptor; PRV; Singing mice; Vocal-motor; Vocalization
    DOI:  https://doi.org/10.1016/j.yhbeh.2026.105890
  7. Am J Physiol Gastrointest Liver Physiol. 2026 Feb 16.
    Sex-Specific Differences in Liver DNA Methylation Patterns and Epigenetic Aging in Mice.
    Shant Apelian, Ramanaiah Mamillapalli, Abdullah Ucar, Nimisha Gawde, Hugh S Taylor.
      Background: Biological sex has been shown to influence aging outcomes, contributing to distinct trajectories in disease susceptibility and lifespan. DNA methylation patterns provide a quantitative measure of biological aging. This study investigated whether aged male and female mice display distinct liver DNA methylation patterns and differences in epigenetic aging. Methods: Liver samples were collected from 17 aged c57BL/6 mice (6 males, 11 females). Genomic DNA was extracted and bisulfite-converted prior to targeted enrichment of 2,045 murine age-associated CpG loci. Biological age (DNAge®) was estimated using a previously developed DNA methylation-based predictor generated through elastic net regression. The difference (ΔDNAge®) between DNAge® and chronological age was computed. Sex-specific differences were assessed by comparing site-specific methylation ratios, ΔDNAge® values, and through principal component analysis (PCA) and multiple linear regression. Results: Twelve CpG sites across six genes (Fam84b, Zswim6, Hsf4, Mn1, Qprt, and Rapgefl1) showed significant sex-associated differences in methylation. Fam84b demonstrated the largest and most consistent sex-associated effect, with all three associated CpG sites showing higher methylation in males (regression coefficients: -0.204, -0.281, -0.294). Zswim6 exhibited consistent lower methylation ratios in females, while the other genes showed higher methylation in females. There were no sex differences in biological age or ΔDNAge® (p = 0.596). Conclusions: Although the epigenetic clock did not reveal differences between sexes in aging, aged mice did exhibit sex-specific liver methylation patterns different from those reported in younger mice, suggesting that sex-dependent epigenetic changes may emerge later in life and may reflect sexual dimorphism in liver function with age.
    Keywords:  Aging; DNA Methylation; Epigenesis; Genetic; Liver; Sex
    DOI:  https://doi.org/10.1152/ajpgi.00322.2025
  8. Geroscience. 2026 Feb 17.
    Treatment with a selective androgen receptor modulator (RAD140) is linked to better cardiac function, with male-specific effects that are graded by interleukin-6.
    Stefan S Heinze, David G Sapp, Alexander P Young, Susan E Howlett.
      Low testosterone levels are associated with impaired cardiac function and elevated circulating inflammatory markers, which are mechanistically related. Selective androgen receptor (AR) modulators (SARMs) can stimulate ARs and mimic testosterone. Whether SARMs affect cardiac structure or function and if circulating inflammatory markers grade these changes is unclear. We investigated the effects of a SARM (RAD140) on cardiac function and structure in older male and female mice and explored how systemic inflammatory markers relate. Older (23-month-old) male and female mice were treated with RAD140 (5 mg/kg/day) for 6-weeks. Left ventricular (LV) structure and function were measured with echocardiography. Serum cytokine levels were assessed with a multiplex assay, and LV gene expression was tested. RAD140 treated males and females had higher ejection fraction (+ 10.4%), stroke volume (+ 9.6 µL) and cardiac output (+ 4.5 mL/min), versus controls. However, RAD140 treated males had better markers of cardiac function, including myocardial strain (-5.8%) and isovolumic relaxation times (-4.7 ms) compared to controls, with lesser or opposite effects in females. Higher levels of interleukin-6 correlated with worse global circumferential strain in males, but not females. qPCR analysis for genes coding proteins related to cardiac function and structure revealed no differences, although AR mRNA was lower with RAD140 treatment in both sexes. No structural differences were observed. RAD140 treatment may enhance cardiac function in older male mice, but less so in older female mice. Increased circumferential strain in males related to lower interleukin-6 levels, supporting the AR's connecting role between cardiac function and inflammatory markers.
    Keywords:  Cardiac function; Geroscience; Preclinical; Selective androgen receptor modulator; Sex differences
    DOI:  https://doi.org/10.1007/s11357-026-02151-9
  9. Biol Sex Differ. 2026 Feb 18.
    Sex differences in immune modulation: implications for infection, inflammation, and nutritional supplementation.
    Marta Araújo, Ana Mendes-Frias, Ricardo Silvestre.
      The immune system is central to maintaining homeostasis and orchestrating defense against infection and the regulation of inflammatory responses, yet its activity is far from uniform across individuals. Sex differences profoundly shape immune responses, with sex hormones driving distinct patterns of susceptibility to infectious diseases and inflammatory conditions. Nutrition further adds a powerful layer of modulation: vitamins, amino acids, and other bioactive compounds influence immune function and disease outcomes, often in a sex-dependent manner. The microbiome, whose composition is itself influenced by sex, is a critical regulator of both intestinal and systemic immune disorders, making it an attractive target for therapeutic intervention. In this review, we examine the dynamic interplay between sex, nutrition, and the immune system, emphasizing their combined impact on infection, inflammation, and immunomodulation. A deeper understanding of these interactions will be key to advancing personalized nutritional and therapeutic strategies designed to optimize immune health.
    Keywords:  Immunology; Immunonutrition; Infectious diseases; Inflammatory diseases; Sex-based differences
    DOI:  https://doi.org/10.1186/s13293-026-00857-1
  10. Gut Microbes. 2026 Dec 31. 18(1): 2631242
    Maternal gut microbiota mediates prenatal stress-induced fetal blood‒brain barrier dysfunction.
    Xuanping Wang, Fang-Yue Zhou, Ting Wu, Chenchi Duan, Xukai Luo, Yicong Meng, He-Feng Huang, Yan-Ting Wu.
      Maternal prenatal stress confers elevated neuropsychiatric risk to offspring, yet the mechanisms underlying fetal neurodevelopmental impairment remain elusive. The gut microbiota has emerged as a key regulator of brain development and behavior. However, the mechanisms mediating the interactions between the microbiota and the developing brain are still poorly understood. Here, utilizing a prenatal stress mouse model integrated with multi-omics approaches, comprehensive behavioral assays, and molecular validations, we demonstrate that prenatal stress not only induces maternal gut microbiota dysbiosis during pregnancy but also, more critically, leads to fetal blood‒brain barrier (BBB) developmental defects and subsequent abnormalities in emotional behavior and cognitive function in adult offspring. Maternal probiotic supplementation during gestation can reverse both gut microbial dysbiosis and fetal BBB dysfunction. Notably, transcriptomic analysis reveals that the maternal gut microbiota modulates interferon-β (IFN-β) signaling along the placenta‒fetal brain axis under stress. Furthermore, metabolomic profiling suggests that prenatal stress exposure profoundly influences the maternal fecal and serum metabolome. In conclusion, our findings establish a placenta‒brain axis wherein maternal microbial signals orchestrate fetal neurovascular development, identifying microbiota-targeted interventions as a neuroprotective strategy.
    Keywords:  Prenatal stress; blood–brain barrier; gut microbiota; interferon β pathway; tryptophan
    DOI:  https://doi.org/10.1080/19490976.2026.2631242
  11. Biol Sex Differ. 2026 Feb 19.
    Sex chromosome-dependent epigenetic regulation underlies sex-specific H4 acetylation at the aromatase promoter in the developing mouse amygdala.
    C Sosa, L E Cabrera-Zapata, C D Cisternas, M A Arevalo, M J Cambiasso.
       BACKGROUND: Sexual differentiation of the brain is a complex ontogenetic process orchestrated by genetic and hormonal influences, leading to sex‑specific physiological and behavioral traits in adulthood. In mammals, the sex chromosome complement (SCC) contributes to this process by encoding unequal genetic information in XX and XY cells. Furthermore, SCC upregulates aromatase and estrogen receptor β (ERβ) expression in amygdala neurons of XY compared to XX embryos at embryonic day (E) 14. These molecules are critically implicated in the steroid-dependent programming of neural circuits during the subsequent critical window of sexual differentiation (E17-PN10). Since epigenetic mechanisms play a key role in specific target gene expression forming a layer of gene regulation, we aimed to contribute to a better understanding of their impact on the sexual differentiation of the brain.
    METHODS: Four Core Genotypes mouse model was employed to study the epigenetic machinery involved in DNA methylation and histone deacetylation in different brain regions (amygdala, hypothalamus, and cortex) to elucidate the underlying epigenetic landscape at E14 by RT-qPCR. Amygdala primary neuronal cultures were then established to evaluate the epigenetic regulation of Cyp19a1 (aromatase) and Esr2 (ERβ) expression. To assess this, pharmacological inhibition of DNA methylation, using zebularine, as well as Chromatin Immunoprecipitation (ChIP-qPCR) assays were performed.
    RESULTS: Sex-specific expression of DNA methyltransferases 3a and 3b, along with histone deacetylases 2 and 8, was higher in XX than XY embryos in a region- and developmental stage- dependent manner. Pharmacological inhibition of DNA methylation did not significantly alter aromatase expression in male or female amygdala neuronal cultures under the conditions tested. However, ChIP-qPCR assays revealed a selective enrichment of Acetyl-H4 at the Cyp19a1 promoter in male cultures that was not observed in females. No significant enrichment of the examined epigenetic marks was detected at the Esr2 promoter.
    CONCLUSIONS: Acetylation of histone H4 contributes to promoting the higher Cyp19a1 expression previously observed in male neurons. Our findings support a model in which SCC plays a role in the epigenetic regulation of aromatase, a key enzyme involved in hormone-driven sexual differentiation of the male brain. Furthermore, the presence of two X chromosomes shapes a distinct epigenetic landscape in the brain during early development, highlighting the influence of chromosomal sex on the neurodevelopmental programming.
    Keywords:  Aromatase; DNA methylation; Histone acetylation; Sex chromosome complement; Sexual differentiation
    DOI:  https://doi.org/10.1186/s13293-026-00854-4
  12. Compr Psychoneuroendocrinol. 2026 Feb;25 100338
    The effect of gender-affirming hormonal treatment on personality traits - a NEO-PI-R study.
    Mats Holmberg, Alex Wallen, Ivanka Savic.
       Introduction: Gender-affirming hormone therapy is a crucial component of the medical transition for many transgender individuals. While there are well-established differences in personality traits between cisgender men and women, the effects of gender-affirming hormone therapy on these traits in transgender individuals remain largely unexplored.
    Aims: The primary aim of this study was to investigate whether gender-affirming hormone therapy affects personality traits in transgender individuals.
    Materials and methods: Adult transgender persons referred for gender-affirming hormone therapy to ANOVA, Center for Andrology, Sexual Medicine, and Trans Medicine at Karolinska University Hospital, Stockholm, Sweden, completed the NEO-PI-R inventory once before starting hormone therapy and once after a minimum of six months of either anti-androgen and estradiol treatment or testosterone therapy. Changes in scores were analyzed using the Wilcoxon Signed-Ranks Test. Patients who had any known hormonal, chromosomal, psychiatric, neurological, or other major medical disorders were excluded from the study.
    Results: At baseline, the assigned female at birth (AFAB) had significantly higher NEO-PI-R scores in the dimension "Agreeableness" and the facets E5 "Excitement seeking" and A2 "Straightforwardness" compared to the assigned male at birth (AMAB). With treatment, the AMAB showed an increase in O3 "Feelings" (md = 2.00; IQR = 0.00-11.50; p = 1.5E-02) and the AFAB showed a decrease in "Neuroticism" (md = -2.00; IQR = -5.50-1.00; p = 3.8E-02), N3 "Depression" (md = -3.00; IQR = -8.25-3.00; p = 2.8E-02), and N6 "Vulnerability" (md = -4.50; IQR = -9.00-2.00; p = 90E-03), as well as an increase in "Actions" (median = 4.00; IQR = -2.50-8.00; p = 1.7E-02). After treatment, the greatest difference between the groups was seen in N6 "Vulnerabiliy". In AMAB, significant negative correlations between the change in NEO-PI-R score and the change in estradiol were found in 2 dimensions and 6 facets.
    Conclusions: Few changes in personality traits were observed, but they aligned with expectations based on established sex differences in personality traits. In general, more changes were observed in the testosterone treated group. The reduction in "Neuroticism" and "Vulnerability" in the AFAB with treatment, but a worsening or no change in the AMAB may be concerning. Further studies are needed to solidify these results and explore the underlying causes.
    Keywords:  Gender-affirming hormone therapy; Personality traits; Transgender persons
    DOI:  https://doi.org/10.1016/j.cpnec.2026.100338
  13. J Steroid Biochem Mol Biol. 2026 Feb 15. pii: S0960-0760(26)00024-5. [Epub ahead of print] 106958
    Review on 11-Oxygenated steroids in hormone-related diseases: polycystic ovary syndrome, endometrial cancer, prostate cancer.
    Xiaoman Jin, Henrica M J Werner, Andrea Romano.
      11-oxygenated androgens and oestrogens are biologically active molecules and have increasingly recognised roles in hormone dependent diseases. However, a comprehensive synthesis of existing evidence across major sex hormone-related conditions is still lacking. This review summarises current literature investigating the associations between 11-oxygenated sex steroids and three hormone dependent disorders - polycystic ovary syndrome (PCOS), endometrial cancer (EC), and prostate cancer (PC). Limitations and potential biases in current literature are discussed. This review highlights the emerging relevance of 11-oxygenated androgens in both men and women and emphasises the need for mechanistic and prospective studies to clarify their role in disease initiation, progression, and therapeutic resistance. The potential role of 11-oxygenated oestrogens in hormone dependent diseases remains unexplored.
    Keywords:  11-oxygenated androgens; 11-oxygenated oestrogens; PCOS; endometrial cancer; prostate cancer
    DOI:  https://doi.org/10.1016/j.jsbmb.2026.106958
  14. BMC Genomics. 2026 Feb 19.
    Escape from X inactivation varies across genes and tissues and shapes sex-biased sex chromosome gene expression.
    Alex R DeCasien.
      Sex differences in human health and disease are shaped by complex interactions between hormones, environment, and genetic factors - including those associated with sex chromosomes. While X chromosome inactivation (XCI) in females generally silences one copy of the X to equalize dosage with males, a subset of genes "escape" XCI and remain expressed from both X chromosomes. In this study, I integrate allele-specific expression data from three females with non-mosaic XCI, sex-biased expression profiles from over 40 tissues, and enhancer activity data from GTEx to explore how variation in the magnitude of XCI escape contributes to sex-biased gene expression across the human body. I confirm that female-biased expression on the X chromosome is a poor proxy for escape from XCI. I find that XCI extends into the pseudoautosomal region (PAR) and that the extent of inactivation strongly predicts male-biased expression of PAR genes. Conversely, stronger escape from XCI in non-PAR X-linked (NPX) genes is associated with more pronounced female-biased expression. Across both PAR and NPX genes, escape patterns are shaped by topologically associating domains (TADs) and sex-biased expression is supported by proximity to sex-biased enhancer activity. These findings reveal a direct, tissue-specific relationship between the strength of XCI escape and the magnitude of sex-biased gene expression, providing a mechanistic framework for understanding how the X chromosome contributes to sex-biased biology.
    Keywords:  GTEx; Sex chromosomes; Sex-biased gene expression; X chromosome inactivation
    DOI:  https://doi.org/10.1186/s12864-026-12611-3
  15. Cureus. 2026 Jan;18(1): e101709
    Association of Serum Estradiol and Testosterone With Hip Fractures in Elderly Men.
    Chiranth Kantharaj, Shishir Murugharaj.
       INTRODUCTION: Hip fractures in the elderly are a major public health concern due to high morbidity, mortality, and long-term disability. While men have a lower incidence of hip fractures than women, the risk rises sharply with age, and outcomes in men are often worse. Sex steroids (especially estrogen and testosterone) play a crucial role in bone metabolism, but their contribution to osteoporosis and fracture risk in elderly men remains under-investigated, particularly in diverse populations. This prospective case-control study aimed to determine whether serum estradiol and testosterone levels differ significantly between elderly South Indian men with osteoporotic hip fractures and age-matched healthy controls.
    METHODS: A prospective case-control study was conducted on men over 55 years of age at a South Indian tertiary hospital (March-May 2022). Fifty men with osteoporotic hip fractures (cases) and 50 age-matched healthy male controls were recruited. Clinical data (age, body mass index, smoking status) were collected, and serum total estradiol and testosterone levels were measured using enzyme-linked fluorescent immunoassay. Overt androgen deficiency was defined as total testosterone <2 ng/mL, and possible deficiency as 2-4 ng/mL. Group comparisons were performed using independent t-tests or Mann-Whitney tests for continuous variables and Fisher's exact test for categorical variables, with significance set at p<0.05.
    RESULTS: The majority of hip fracture cases were in the 65-75 years age group (25, 50%). Cases had a high prevalence of low sex hormones: 22 (44%) had overt androgen deficiency and 26 (52%) had possible androgen deficiency, compared to only two (4%) of controls with testosterone <2 ng/mL. Mean serum testosterone in cases was significantly lower than in controls (2.40±1.12 vs. 4.22±1.62 ng/mL, p<0.001), and mean estradiol was also lower in cases (32.07±10.08 vs 41.88±17.99 pg/mL, p=0.008). Low estradiol levels were more frequent in cases: only 21 (42%) of cases had high-normal estradiol (≥34.3 pg/mL) vs. 30 (60%) of controls. There were no significant differences in body mass index or smoking status between cases and controls (p>0.05).
    CONCLUSION: Elderly men with hip fractures had significantly lower serum testosterone and estradiol levels than age-matched controls, demonstrating an association between reduced sex hormone levels and hip fracture status. These findings support a possible role of sex hormones in male skeletal health, but causal relationships and therapeutic implications cannot be inferred from this study and require confirmation in larger prospective investigations.
    Keywords:  bone health; elderly men; estradiol; hip fracture; testosterone
    DOI:  https://doi.org/10.7759/cureus.101709
  16. Front Neuroendocrinol. 2026 Feb 12. pii: S0091-3022(26)00006-3. [Epub ahead of print] 101236
    Not just neurons: Glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.
    Nicole Horan, Tori Keefauver, Marianne L Seney.
      Sex differences are fundamental determinants of the neurobiology of substance use disorders (SUDs), modulating withdrawal severity, relapse risk, and treatment response. Despite this, prior research has largely studied males and ignored sex differences. Growing bodies of evidence suggests glial cells mediate these sex differences, particularly during withdrawal. In this review, we begin describing baseline sex differences and known glial sex differences at homeostasis. We then examine clinical and preclinical findings describing alterations in glial cells during withdrawal. We describe how glial sex differences are region-specific to areas implicated in reward-induced dysfunction. We conclude with a description of how glial sex differences during withdrawal likely drive sex differences in relapse vulnerability. Our synthesis posits glial cells as key mediators of sex differences in SUD withdrawal. Future investigations focused on glial pathologies could uncover sex-specific, targetable mechanisms to improve treatment and promote sustained remission in both males and females.
    Keywords:  Amygdala; Astrocytes; Cortex; Glia; Microglia; Nucleus accumbens; Oligodendrocytes; Sex differences; Substance use disorder; Withdrawal
    DOI:  https://doi.org/10.1016/j.yfrne.2026.101236
  17. J Oral Biosci. 2026 Feb;pii: S1349-0079(26)00023-X. [Epub ahead of print]68(1): 100755
    Mouse strain and sex differences in the number and distribution of salivary gland IgA plasma cells.
    Midori Maekawa, Yukinori Tanaka, Kentaro Mizuta, Shunji Sugawara.
       OBJECTIVE: Salivary immunoglobulin A (IgA) produced by IgA plasma cells (PCs) in the salivary glands (SGs) plays a key role in maintaining immune homeostasis in the oral mucosa. We investigated differences by sex and mouse strain in salivary IgA concentration and IgA PC distribution among the major SGs.
    METHODS: Pilocarpine-induced saliva was collected from male and female BALB/c and C57BL/6 mice, and salivary IgA concentrations were assessed using ELISA. Cells were isolated from the parotid, submandibular, and sublingual glands and analyzed using flow cytometry to quantify IgA PCs.
    RESULTS: Salivary IgA concentrations were higher in BALB/c mice than in C57BL/6 mice, with no sex-related differences. Total numbers of IgA PCs in the three major SGs were consistently higher in BALB/c mice than in C57BL/6 mice, with no sex differences. In both strains, male mice exhibited parotid gland-dominant distribution of IgA PCs, whereas female mice exhibited submandibular/sublingual gland-dominant distribution.
    CONCLUSIONS: The present results reveal distinct strain and sex differences in salivary IgA concentrations and in numbers and distribution of SG IgA PCs.
    Keywords:  Mouse strain differences; Plasma cells; Salivary IgA; Salivary glands; Sex differences
    DOI:  https://doi.org/10.1016/j.job.2026.100755
  18. Brain Behav Immun. 2026 Feb 12. pii: S0889-1591(26)00233-3. [Epub ahead of print] 106485
    Chronic airway inflammation is associated with sex-dependent changes in behaviour, neuroinflammation and the gut microbiome.
    Shivani Mandal, Marie Armbruster, Ritu Mann-Nüttel, Paul Forsythe.
      Asthma is a chronic inflammatory lung disease linked to a higher prevalence of comorbid mood disorders, such as anxiety and depression, though the underlying pathophysiology and the influence of biological sex remain poorly understood. To investigate this complex relationship, we employed a chronic house dust mite (HDM) exposure model in male and female C57BL/6 mice, examining the sex-dependent effects of allergic airway inflammation across systemic, neuroimmune, behavioural, and gut microbiome axes. Chronic HDM exposure successfully induced hallmark features of allergic airway disease in both sexes. While females exhibited significantly higher levels of most measured airway and systemic inflammatory cytokines compared to males, the neuroinflammatory and behavioural changes were more pronounced in males. HDM-exposed males showed increased hippocampal microglial activation, enhanced mast cell presence, and widespread hypothalamic transcriptional alterations. Females, however, exhibited increased astrocytic activation and enrichment of the estrogen response pathway, suggesting a differential, potentially protective, glial responses. Behaviourally, males displayed reduced grooming and greater despair-like behaviour, consistent with depressive-like phenotypes, whereas females showed reduced grooming only. Parallel analyses revealed that males experienced more extensive gut microbial disruption, particularly in the small intestine, including reductions in taxa previously associated with depressive behaviours (Romboutsia, Turicibacter) and broader shifts in microbial metabolic pathways. The observation that males, despite lower systemic inflammation, exhibit greater neuroinflammatory signatures, more extensive hypothalamic changes, and distinct behavioural deficits underscores the necessity of a sex-informed approach to understanding and mitigating the neuropsychiatric sequelae of chronic allergic asthma.
    Keywords:  Allergic asthma; Chronic airway inflammation; Depressive-like behaviour; House dust mite; Hypothalamus; Microbiome; Neuro-inflammation; Sex-differences; Small intestine
    DOI:  https://doi.org/10.1016/j.bbi.2026.106485
  19. Int J Womens Health. 2026 ;18 559370
    Dual Role of the Endometrial Microbiome-Immune Axis: From Endometrial Homeostasis to Reproductive Disorders.
    Xiaochuan Yu, Yating Zhang, Li Juan Shi, Huali Wang.
      The homeostasis of the uterine environment is crucial for reproductive health. Recent studies have revealed the complex interplay between the endometrial microbiome, immune system, and the endometrium. Under normal physiological conditions, the microbiome, primarily composed of Lactobacillus species, promotes a healthy reproductive environment by maintaining local immune homeostasis, inhibiting the growth of pathogenic microorganisms, and regulating the integrity of the endometrial barrier. However, dysbiosis can abnormally activate local immune responses, disrupting the immune tolerance mechanisms of the endometrium and thereby compromising pregnancy maintenance and overall reproductive health. This study uniquely highlights the role of the endometrial microbiome in modulating immune responses specifically within the uterine environment, a critical factor for reproductive success. Our findings also suggest novel therapeutic strategies targeting microbiome modulation and immune regulation, offering promising avenues for improving reproductive health outcomes. This review aims to explore the regulatory mechanisms of the microbiome-immune axis in both physiological and pathological conditions, with a particular focus on how these interactions specifically influence the uterine environment, while also considering the broader implications of microbiome-immune interactions throughout the entire body. We will analyze its potential role in reproductive health issues and discuss new therapeutic strategies based on microbiome and immune modulation.
    Keywords:  dysbiosis; endometritis; endometrium; immune response; immune tolerance; infertility; microbiota; recurrent miscarriage; reproductive health
    DOI:  https://doi.org/10.2147/IJWH.S559370
  20. PLoS One. 2026 ;21(2): e0342456
    Sexual dimorphism in the cell number of the adult Drosophila brain.
    Narendra Pratap Singh, Susan T Harbison.
       BACKGROUND: Sexual dimorphism in animal behavior is common and may originate from differences in brain structure or function. In Drosophila, substantial male and female specific differences in gross brain anatomy, neuronal wiring, and behavior have been observed. However, it is not known whether global differences in the brain anatomy are strictly due to differences in neuronal patterning or if differences in cell number may also play a role.
    PRINCIPAL FINDINGS: During optimization of the assay for transposase-accessible chromatin with sequencing (ATAC-seq) to analyze gene regulation in adult brain cells we observed a need for more brain tissue in males compared to females. This suggested that male brains might have fewer cells. To test this hypothesis, we isolated total nuclei from adult brains and counted them using a flow cytometer. We found that female fly brains have approximately 30% more cells than male brains. These differences in cell number also correlated with differences in the physical size of the brain.
    CONCLUSIONS: Our results suggest that male and female brains are not only differently wired but also have global differences in cell number that should be considered when analyzing differences in their behavior.
    DOI:  https://doi.org/10.1371/journal.pone.0342456
  21. Rheumatology (Oxford). 2026 Feb 18. pii: keag087. [Epub ahead of print]
    Hormonal transitions across the lifespan shape susceptibility to Sjogren's disease.
    Eliza C Diggins, Melodie L Weller.
       OBJECTIVES: Sjogren's disease (SjD) shows a strong female predominance, but the contribution of age-related hormone changes to this sex bias remains uncertain. We investigated whether natural hormonal transitions across the lifespan align with variation in male and female prevalence of SjD.
    METHODS: Electronic health records from 101 856 SjD patients and 1.33 million controls were analyzed. Sex-specific prevalence was compared with serum testosterone, estradiol, and sex hormone-binding globulin (SHBG) levels. Population-level hormone distributions from the National Health and Nutrition Examination Survey (NHANES) were incorporated using imputation. Generalized linear models evaluated associations between hormone fluctuations and sex prevalence across age groups.
    RESULTS: Male prevalence among SjD patients peaked during early childhood (30.1% [95% CI: 26.2-34.1]), declining sharply in late puberty into adulthood (9.8% [95% CI: 9.5-10.2]), and rose again in older adults (13.5% [95% CI: 13.3-13.8]). These non-linear shifts paralleled age-dependent trajectories of testosterone and estradiol. Hormone concentrations did not differ significantly between SjD patients and controls, indicating that physiological transitions, rather than abnormal levels, align with disease risk.
    CONCLUSION: Age-dependent hormonal changes correspond with evolving sex bias in SjD, challenging the static 9:1 female-to-male paradigm. These findings highlight the role of age-related hormonal dynamics in shaping autoimmune susceptibility.
    Keywords:  Sjogren’s Disease; Sjogren’s syndrome; autoimmunity; estrogen; hormonal regulation; hormone-mediated pathogenesis; sex bias; sex hormones; testosterone
    DOI:  https://doi.org/10.1093/rheumatology/keag087
  22. Circulation. 2026 Feb 17. 153(7): 534-535
    Redefining Cardiovascular Medicine: The Journey From "Does Sex Matter?" to "How Does Sex Matter?"
    Stacey E Rosen.
      
    Keywords:  cardiovascular diseases; sex differences; sex factors; women’s health
    DOI:  https://doi.org/10.1161/CIRCULATIONAHA.125.079070
  23. Reproduction. 2026 Feb 15. pii: xaag025. [Epub ahead of print]
    Comparison of intra-ovarian metabolic environment between women with or without PCOS undergoing in vitro fertilization.
    A Gervais, G Ostinelli, J Faubert, M-C Battista, B Carranza-Mamane, H B Lavoie, J-P Baillargeon.
      Evidence suggest that lipotoxicity can cause hyperandrogenesis, but little is known about the intra-ovarian environment of women with polycystic ovary syndrome (PCOS) and whether it displays features associated with lipotoxicity. The objective of this secondary analysis was to compare follicular fluid concentrations of testosterone, markers of lipid, lipid metabolism and inflammation between women with PCOS and without PCOS. We conducted a controlled cross-sectional study on 80 participants. Medical records were used to determine PCOS diagnosis: 15 women were identified as having PCOS, while 65 had a negative diagnosis. Inclusion criteria were 18 and 40 years old with a body mass index raging between 18 and 40 kg/m2. Follicular fluid was analysed for total testosterone, non-esterified fatty acids (NEFA), triglycerides, NEFA metabolites (acylcarnitines and C16/C13 ratio) and inflammatory cytokines. Compared to women without PCOS, women with PCOS had increased follicular fluid levels of testosterone (7.08 nM vs 0.29 nM), triglycerides (0.30 nM vs 0.17 nM), palmitoylcarnitine (43.7 nM vs 28.4 nM) IL-6 (13.04 pg/mL vs 8.9 pg/mL), while TNF-α remained similar. These differences remained statistically different after adjustment for BMI, except for IL-6. These group differences were also confirmed in paired analyses of 13 BMI-matched pairs of PCOS vs non-PCOS women, exception made for IL-6. In conclusion, intra-ovarian inflammation, but more importantly, lipid overexposure, may play a role in the pathogenesis of PCOS, probably through lipotoxic effects.
    Keywords:   in vitro fertilization; Follicular Fluid; Lipotoxicity; Polycystic Ovary Syndrome
    DOI:  https://doi.org/10.1093/reprod/xaag025
  24. Nat Rev Immunol. 2026 Feb 16.
    Harnessing mucosal immunity for protective vaccines.
    Dong-Il Kwon, Sachin H Bhagchandani, Stephen A Ehrenzeller, Akiko Iwasaki.
      Mucosal surfaces are primary entry sites for many infectious pathogens, yet parenteral vaccination alone often fails to elicit effective mucosal immunity. Mucosally delivered vaccines offer a promising strategy for reinforcing frontline defences and inducing localized, pathogen-specific immune responses. Recent studies indicate that mucosal vaccines elicit tissue-resident memory T and B cells, along with robust local antibody secretion, to prevent infection and transmission. However, achieving sterilizing immunity at mucosal sites proves challenging owing to the complex immune environments consisting of epithelial barriers, varying mucus composition, pH differences and hormonal influences. In this Review, we outline how specialized immune-inductive and effector mechanisms across distinct mucosal compartments contribute to protective immunity and discuss emerging strategies to harness multilayered mucosal immunity to develop safe, effective vaccines that elicit durable protection.
    DOI:  https://doi.org/10.1038/s41577-026-01273-7
  25. Front Immunol. 2026 ;17 1743572
    B cells and iBALT in TB immunity & pathogenesis.
    Taru S Dutt, Robert Krause, David Hertz, Marcela Henao-Tamayo, Alasdair Leslie, Bianca Schneider.
      B cells play a crucial role in immunity against various infectious diseases. However, their role in tuberculosis (TB) has been largely understudied. Emerging evidence suggests that B cells actively shape immune responses in TB. Beyond their classical functions, B cells contribute to the formation of inducible bronchus-associated lymphoid tissue (iBALT), a tertiary lymphoid structure (TLS) that enhances localized immune responses in the lungs. As iBALT is a site for B-T cell interactions and the generation of high-affinity antibodies, recent studies suggest that sex differences in iBALT formation influence TB immunity. This review synthesizes evidence from both TB and non-TB models to highlight the expanding role of B cells and iBALT, underscoring their potential implications for vaccine development and immunotherapy.
    Keywords:  B cells; TLS; antibodies; iBALT; sex differences; tuberculosis
    DOI:  https://doi.org/10.3389/fimmu.2026.1743572
  26. Menopause. 2026 Feb 17.
    Endogenous sex hormones, sex hormone-binding globulin, and muscle health: insights into sarcopenia and sarcopenic obesity from the Women's Health Initiative.
    Amar Osmancevic, Bledar Daka, Joseph C Larson, Matthew Allison, Richard O Burney, Aladdin H Shadyab, Jane A Cauley, Carolyn J Crandall.
       OBJECTIVE: The relationship between sex hormones and lean body mass in postmenopausal women is unclear. To address this, we conducted a longitudinal observational study using data from the Women's Health Initiative study.
    METHODS: We analyzed endogenous serum sex hormones and sex hormone-binding globulin (SHBG) at baseline in 1,565 postmenopausal women not using hormone therapy, who underwent 3 lean body mass measurements over 6 years. Sex hormone concentrations were assessed at baseline using radioimmunoassay. Lean body mass was assessed by dual-energy x-ray absorptiometry at baseline, year 3 and 6. Free estradiol and free testosterone concentrations were calculated. Each sex hormone was analyzed independently of the other hormones. Associations between sex hormones or SHBG were examined using repeated-measures linear regression for lean mass and repeated-measures logistic regression for sarcopenia/sarcopenic obesity. Regression models were adjusted for age, race/ethnicity, lifestyle, and metabolic confounders.
    RESULTS: Concentration of free testosterone in the highest quartile was associated with a 55% lower odds for sarcopenia compared with the lowest quartile (OR: 0.45; 95% CI: 0.25-0.81). Similarly, individuals with the highest concentration of free estradiol had a 54% reduced odds of sarcopenia (OR: 0.46, 95% CI: 0.28-0.76). Conversely, a higher concentration of SHBG at baseline was significantly associated with reduced total lean mass and a higher odds of sarcopenia.
    CONCLUSION: Among postmenopausal women, higher SHBG concentrations at baseline were associated with lower lean body mass and a higher odds of sarcopenia, while higher free estradiol and free testosterone concentrations were associated with a lower odds of sarcopenia.
    Keywords:  Endocrinology; Postmenopause; Sarcopenia; Sarcopenic obesity; Sex hormones; Skeletal muscle; Women.
    DOI:  https://doi.org/10.1097/GME.0000000000002734
  27. Sci Immunol. 2026 Feb 20. 11(116): eadx0292
    Monocyte-derived IL-10 drives sex differences in pain duration.
    Jaewon Sim, Elizabeth O'Guin, Chiho Sugimoto, Sophie Laumet, Karli Monahan, Matthew P Bernard, Samuel A McLean, Liz M Albertorio-Sáez, Ying Zhao, Hariharan Ramakrishnan, Sabrina de Souza, Olivia C Eller, Christine J Smoyer, Kyle M Baumbauer, Matthias Mack, Joseph K Folger, Alfred J Robison, Sarah D Linnstaedt, Geoffroy Laumet.
      Women frequently experience longer-lasting pain than men, indicating delayed pain resolution, but the mechanisms underlying this sex difference remain unclear. Here, we show that interleukin-10+ (IL-10+) monocytes resolve inflammatory pain by signaling to IL-10R1+ sensory neurons in a mouse model of skin inflammation. Male mice exhibited faster pain resolution than females, which was associated with higher numbers of IL-10+ monocytes. In both sexes, pain resolution was impaired by deleting Il10 from monocytes or Il10ra from sensory neurons. Androgen signaling promoted IL-10 production by monocytes, driving sex differences in IL-10+ monocyte abundance. Enhancing IL-10+ monocytes with resolvin D1 accelerated pain resolution in both sexes. In humans, pain resolved faster in men than in women after traumatic injury and was associated with higher circulating monocytes and IL-10 levels in men. These findings identify a role for peripheral IL-10+ monocytes in sex-specific pain resolution and highlight immune mechanisms that may prevent chronic pain.
    DOI:  https://doi.org/10.1126/sciimmunol.adx0292
  28. Microbiol Spectr. 2026 Feb 18. e0279125
    Bacterial microbiome analysis of vaginal, cervical, and endometrial samples in patients with adenomyosis during the window of implantation.
    Nika Troha, Tomaž M Zorec, Lea Hošnjak, Katja Strašek Smrdel, Andraž Celar Šturm, Vesna Šalamun, Snježana Grazio Frković, Eda Vrtačnik Bokal, Mario Poljak.
      Adenomyosis is a chronic gynecological condition affecting a substantial portion of women of reproductive age. With symptoms including abnormal uterine bleeding, chronic pelvic pain (CPP), dysmenorrhea, and infertility, poor response to symptomatic treatment and unfavorable outcomes of assisted reproductive technologies, it remains a significant diagnostic and therapeutic challenge. Here, we analyzed microbial compositions of the reproductive tract of women with adenomyosis (n = 33) in comparison with healthy controls (n = 31). Vaginal, cervical, and endometrial samples were collected using minimally invasive transcervical sampling techniques on the 22nd day of the menstrual cycle, during the so-called window of implantation. 16S rRNA was amplified and recorded using the next generation sequencing. Bioinformatic and statistical analysis focused on quantitative taxonomical characterization of the specimens' microbiomes. Vaginal bacterial microbiome composition was consistent across the three anatomical sites. Compared with the control group, adenomyosis was associated with Lactobacillus iners, whereas Lactobacillus gasseri and Gardnerella vaginalis were negatively associated with adenomyosis and its clinical symptoms. G. vaginalis, typically considered a pathogen, was highlighted as an important dominant microbiome replacement for lactobacilli, more so in healthy women than in women with adenomyosis. Anaerococcus prevotii, Peptoniphilus grossensis, and Peptrostreptococcus anaerobius also showed weak correlation to adenomyosis. Differences in taxa abundance were detected in association with adenomyosis clinical symptoms. L. iners was associated with dysmenorrhea, heavy menstrual bleeding (HMB), as well as CPP. Prevotella disiens, Prevotella timonesis, and Dialister micraerophilus were associated with dysmenorrhea and Peptoniphilus grossensis with HMB, respectively. L. gasseri and L. jensenii appeared to anticorrelate with these symptoms.
    IMPORTANCE: Adenomyosis poorly responds to treatment and assisted reproductive technologies. Here, we report a comprehensive 16S rRNA-based analysis of vaginal, cervical, and endometrial samples, obtained minimally invasively (transcervically) in a cohort of Caucasian women during the receptive phase of endometrium. Results revealed the least invasive option, vaginal microbiome sampling, reliably predicts the microbiome compositions of cervix and endometrium. We showed substantial variation in microbial composition of adenomyosis patients. L. iners, a species with specific functional traits, was consistently associated with adenomyosis presence and related symptoms. This finding suggests microbiome remodeling as a viable novel therapeutic option for adenomyosis. Furthermore, our findings indicate that the pathogenic role of G. vaginalis may be context-dependent. Ongoing genomic and ecological profiling is essential to clarify Gardnerella's dual commensal-pathogenic nature. Previous adenomyosis studies have mostly focused on the vaginal microbiome, whereas the endometrial microbiome has rarely been studied and never in the time of window of implantation.
    Keywords:  Gardnerella vaginalis; Lactobacillus gasseri; Lactobacillus iners; adenomyosis; infertility; microbiome; reproductive health; reproductive tract; window of implantation
    DOI:  https://doi.org/10.1128/spectrum.02791-25
  29. J Reprod Immunol. 2026 Feb 16. pii: S0165-0378(26)00031-8. [Epub ahead of print]174 104862
    Intestinal dysbiosis-related infertility: Effectiveness of probiotics and synbiotics supplementation.
    Samaneh Abdolmohammadi-Vahid, Vida Ebrahimi, Mohammad Sadegh Soltani-Zangbar, Alireza Mansouri, Leili Aghebati-Maleki.
      Infertility, which impacts around 17 % of couples globally, is becoming more closely associated with gut dysbiosis and an imbalance in immune and metabolic functions. Probiotics like Lactobacillus and Bifidobacterium can help restore the balance of gut bacteria, boost insulin sensitivity, and regulate reproductive hormones. On the other hand, synbiotics, combinations of probiotics and prebiotics, work to enhance microbial diversity, increase the production of short-chain fatty acids, and improve immune-endocrine function. Research indicates that synbiotics could be more effective than probiotics in enhancing metabolic, hormonal, and inflammatory parameters related to infertility, especially in women with PCOS; however, evidence supporting superiority in terms of definitive reproductive outcomes such as pregnancy or live birth rates remains limited. Nevertheless, the favorable safety profiles of both interventions support their further exploration within personalized, microbiota-based infertility strategies.
    Keywords:  Gut–Reproductive Axis; Infertility; Intestinal Dysbiosis; Probiotics; Synbiotics
    DOI:  https://doi.org/10.1016/j.jri.2026.104862
  30. PeerJ. 2026 ;14 e20786
    Metabolomic profiling of follicular fluid reveals unique pathways in endometriosis and infertility etiologies: a pilot study.
    Ping Yu, Dandan Chen, Deshen Han, Xin Jin, Yuhong Li, Fu Wei, Yun Zhang.
       Purpose: This study investigates metabolic profiles in follicular fluid of patients with endometriosis (EM), polycystic ovary syndrome (PCOS), tubal blockage (TB), and unexplained infertility (UEI), assessing their associations with follicular development and in vitro fertilization (IVF) outcomes. It aims to identify metabolic alterations and potential biomarkers for EM diagnosis and personalized reproductive strategies.
    Methods: Follicular fluid samples were collected from 12 infertility patients (3 EM, 3 PCOS, 3 TB, and 3 UEI) undergoing IVF. Metabolomic profiling was performed using liquid chromatography-mass spectrometry (LC-MS), followed by pathway enrichment analysis to identify key metabolic pathways. Statistical analyses were conducted to compare metabolic profiles across groups, assess correlations with follicular development rate (FDR), and evaluate potential biomarkers for EM diagnosis.
    Results: EM patients showed significant metabolic changes, including reduced steroid biosynthesis and elevated thiamine metabolism metabolites, linked to lower FDR. Oxidative stress markers (3-chloro-L-tyrosine, 8-oxoerythraline) were elevated and negatively correlated with FDR. A predictive model identified D-mannosamine, D-galacturonic acid, and 3-chloro-L-tyrosine as potential EM biomarkers with high diagnostic accuracy.
    Conclusion: This study reveals distinct metabolic disruptions in the follicular fluid of EM patients, particularly in steroid biosynthesis and thiamine metabolism pathways, which are linked to impaired follicular development. The identification of specific metabolites as potential biomarkers for EM provides a foundation for developing diagnostic approaches that minimize the need for additional invasive procedures and support personalized assisted reproductive technology (ART) strategies. This pilot study requires further validation to confirm these findings and translate them into clinical practice.
    Keywords:  Biomarkers; Follicular fluid follicular development rate (FDR); Follicular fluid metabolomics; In vitro fertilization (IVF); Infertility etiology
    DOI:  https://doi.org/10.7717/peerj.20786
  31. Nat Microbiol. 2026 Feb 19.
    Conserved CD4+ T cell staphylococcal and streptococcal epitopes enable broad-acting vaccines in mice.
    Jessica Braverman, Ian R Monk, Adrianna M Turner, Asolina Braun, Heran Zhang, Shanzou Chung, Claerwen M Jones, Pirooz Zareie, Nicole L La Gruta, Joanne Rimmer, Glen P Carter, Benjamin P Howden, Nancy Wang, Anthony W Purcell, Timothy P Stinear, Linda M Wakim.
      Vaccines are effective and much-needed tools against bacterial infection, which mitigate multidrug resistance; however, selection of bacterial antigens that elicit protection and contribute to effective vaccines remains challenging. Here we use immunopeptidomics to identify CD4+ T cell vaccine targets in methicillin-resistant Staphylococcus aureus, a clinically significant, antibiotic-resistant bacterium that is susceptible to T cell-mediated control. We identified a highly conserved, immunodominant CD4+ T cell epitope in S. aureus that is derived from the core DNA-binding protein Hu (Hup). This epitope was shared across a range of clinically relevant streptococcal and staphylococcal species, and cross-species-reactive Hup-specific CD4+ T cells were found in both mice and humans. Immunization of mice with the Hup epitope resulted in the development of broadly protective CD4+ T cell immunity capable of limiting disease severity following infection with S. aureus and Streptococcus pneumoniae. These findings suggest that vaccines incorporating antigens derived from core genes conserved across species might confer broad-spectrum protection against multiple clinically relevant, antibiotic-resistant streptococcal and staphylococcal strains.
    DOI:  https://doi.org/10.1038/s41564-026-02265-y
  32. World J Gastrointest Surg. 2026 Jan 27. 18(1): 114445
    Differences in testosterone levels in perianal diseases: A comparative study of abscesses and fistulas.
    Xi Zhang, Qiang Zhang, Min-Jie Wang, Yan-Ting Sun, Jin-Gen Lu.
       BACKGROUND: Anorectal abscess and cryptoglandular anal fistula are common conditions with high recurrence rates, reflecting an incomplete understanding of their pathophysiology. A classic, yet unproven hypothesis proposes that high androgen levels increase infection risk by stimulating anal gland secretion, potentially explaining the male predominance. However, direct evidence regarding sex hormone levels in patients remains scarce. We hypothesized that active perianal infection is associated with significantly altered testosterone (T) levels.
    AIM: To investigate the association between perianal diseases and sex hormone levels and to identify factors associated with T levels.
    METHODS: This cross-sectional study included 249 men: 64 with hemorrhoids, 64 with anorectal abscess, and 121 with anal fistula. Preoperative serum sex hormone levels were measured. Multivariate linear regression identified factors associated with T levels.
    RESULTS: There were no significant differences in age among the three groups at baseline. T levels differed significantly among the groups (P < 0.001). Multivariate regression analysis revealed that in the overall study population, anorectal abscess (B = -2.999, P < 0.001) and body mass index (BMI; B = -0.368, P < 0.001) negatively correlated with T levels. In the abscess group, white blood cell count (B = -0.565, P < 0.001) and BMI (B = -0.298, P = 0.011) negatively correlated with T levels. In the fistula group, BMI (B = -3.866 P < 0.001) and internal opening above the dentate line (B = -4.479, P = 0.048) were associated with lower T levels.
    CONCLUSION: Patients with active perianal infections exhibited a significantly lower T level compared to those with hemorrhoids or fistulas, which is independently associated with systemic inflammation severity and obesity.
    Keywords:  Anal fistula; Anorectal abscess; Body mass index; Cross-sectional study; Inflammation; Perianal diseases; Sex hormones; Testosterone
    DOI:  https://doi.org/10.4240/wjgs.v18.i1.114445
  33. Front Immunol. 2026 ;17 1667720
    Impact of maternal visceral leishmaniasis on sex-specific immune responses and pathogenesis in offspring following homologous infections.
    Haruka Mizobuchi, Chizu Sanjoba, Yasuyuki Goto.
      Leishmania donovani (Ld), the etiological agent of visceral leishmaniasis, has recently been implicated in vertical transmission, raising concerns about the potential impact of maternal infection on offspring immunity and disease susceptibility. Despite this, the effects of maternal Ld infection on the offspring's immune responses and pathogenesis upon homologous infection remain largely uncharacterized. In this study, we investigated the influence of maternal Ld infection on disease outcomes in offspring by challenging offspring born to chronically infected female mice with homologous Ld parasites. Although persistent infection or acquired immune memory was not detected in offspring postnatally, distinct sex-dependent pathological outcomes were observed following challenge. Male offspring exhibited exacerbated erythrophagocytosis by splenic macrophages, leading to marked anemia irrespective of splenic parasite burden. In contrast, female offspring showed aggravated hepatic parasitic proliferation, inflammatory infiltration, granuloma formation, and extensive liver damage. These findings suggest that maternal Ld infection induces long-lasting, sex-specific alterations in the offspring's immune system, particularly affecting macrophage function. This study provides the first evidence that maternal Ld infection differentially shapes the offspring's immunopathological responses to homologous infection in a sex-dependent manner, offering novel insights for risk assessment and the development of sex-informed strategies for disease prevention.
    Keywords:  developmental immune alterations; erythrophagocytosis; granulomatous inflammation; maternal infection; sex-specific immunity; visceral leishmaniasis
    DOI:  https://doi.org/10.3389/fimmu.2026.1667720
  34. Cancer Rep (Hoboken). 2026 Feb;9(2): e70496
    Androgen Receptor Signaling Inhibitors for Metastatic Hormone Sensitive Prostate Cancer in Asians: Indirect Comparison.
    Wei Chen, Soichiro Yoshida, Yasuhisa Fujii.
       BACKGROUND: Androgen receptor signaling inhibitors (ARSI) combined with androgen deprivation therapy (ADT) have demonstrated significant survival benefits in metastatic hormone-sensitive prostate cancer (mHSPC) in several clinical trials. However, data specifically in Asian patients remain limited, with individual subgroup analyses showing trends that did not reach statistical significance. We conducted a pooled analysis to provide additional evidence regarding the efficacy of ARSI plus ADT in Asian patients with mHSPC.
    METHODS: We systematically identified clinical trials reporting overall survival (OS) outcomes for ARSI-based doublet therapy in Asian patients with mHSPC. Individual patient data (IPD) were reconstructed from published Kaplan-Meier curves. Data sources included the TITAN Asian subpopulation analysis, the TITAN Japanese subpopulation, and the LATITUDE Japanese subpopulation. Reconstructed data were validated against original hazard ratios (HR) and curves. Pooled survival analyses were performed for the overall Asian cohort and separately for Japanese patients only.
    RESULTS: A total of 291 reconstructed IPDs were analyzed (146 ARSI plus ADT, 145 placebo plus ADT). In the overall Asian cohort, the 3-year OS was 85.2% with ARSI plus ADT versus 77.6% with placebo plus ADT, representing a 32% reduction in the risk of death (HR = 0.68, 95% CI 0.44-1.03, p = 0.07). In the Japanese subpopulation, 3-year OS was 77.4% versus 72.4%, with a 45% reduction in death risk (HR = 0.55, 95% CI 0.29-1.04, p = 0.07). Neither analysis reached statistical significance.
    CONCLUSION: This exploratory analysis observed a trend toward improved survival with ARSI plus ADT in Asian patients with mHSPC that did not achieve statistical significance. Prospective studies are needed to validate these findings.
    DOI:  https://doi.org/10.1002/cnr2.70496
  35. Conserv Physiol. 2026 ;14(1): coag007
    Pregnancy- and age-associated variation in serum dehydroepiandrosterone concentrations in black and white rhinoceroses.
    Drew M Arbogast, Lara C Metrione, Marieke K Jones, Elizabeth M Donelan, Terri L Roth, Elizabeth W Freeman, Louisa A Rispoli.
      Dehydroepiandrosterone (DHEA) is an important hormone precursor for androgen and oestrogen sex steroids, yet it is understudied in wildlife and has not been measured in rhinoceroses. The objective of this study was to examine serum DHEA concentrations in ex situ black (Diceros bicornis; n = 22 male, 18 female) and white (Ceratotherium simum; n = 25 male, 46 female) rhinoceroses. A commercially available DHEA immunoassay was validated for use with rhino serum, and monthly samples (n = 1029) were analysed. Analytical validation included demonstrating parallel displacement curves between serially diluted standards and pooled extracts, as well as 91% extraction efficiency in a spike and recovery test. Differences in DHEA concentrations relative to species, age, sex and pregnancy status were analysed using linear mixed models. Serum DHEA concentrations were higher (P < 0.001) in black (194 ± 14.2 pg/ml) versus white (123 ± 8.0 pg/ml) rhinoceroses and demonstrated a non-linear relationship with age in both species, with concentrations peaking around 15 years of age before declining thereafter. No sex differences between males and non-pregnant females were detected in either rhinoceros species. White rhinoceros DHEA concentrations were higher (P < 0.001) in pregnant (309 ± 31.9 pg/ml, n = 15) compared to non-pregnant (120 ± 10.4 pg/ml, n = 41) females; pregnant black rhinoceroses similarly produced elevated DHEA concentrations during pregnancy (1092 ± 90.3 pg/ml; n = 2) compared to non-pregnant (229 ± 8.1 pg/ml; n = 17) females. DHEA concentrations also increased throughout gestation particularly during mid- to late gestation in both species. These findings provide new insight into rhinoceros endocrinology and suggest potential utility of DHEA for monitoring pregnancy status.
    Keywords:  Age; biomarker; enzyme immunoassay; gestation; parturition; reproduction
    DOI:  https://doi.org/10.1093/conphys/coag007
  36. Prog Mol Biol Transl Sci. 2026 ;pii: S1877-1173(26)00042-6. [Epub ahead of print]220 267-303
    The human reproductive tract microbiome: A novel source of live biotherapeutics.
    Lekshmi Narendrakumar, Proxima Dhiman, Bhabatosh Das.
      Live biotherapeutics which are live microorganisms with clinically validated therapeutic benefits are rapidly emerging as innovative interventions for a broad spectrum of health disorders. The human reproductive tract, particularly the female vagina is home to specific microbial community that play a vital role in maintaining mucosal immunity, preventing pathogen colonization and supporting successful pregnancy outcomes. Disruption to this microbial balance have been strongly associated with conditions such as bacterial vaginosis (BV), sexually transmitted infections (STI), infertility and pregnancy complications such as pre-term birth. Given the adverse effects of conventional pharmaceutical treatments, microbiome based therapeutic strategies are gaining increasing popularity as safer and more sustainable alternatives. Recent advancements in synthetic biology, genetic engineering and microbiome science have enabled the development of next generation live biotherapeutics that go beyond traditional probiotics which are intended for only maintaining general health. This chapter explores the human reproductive tract microbiome as a novel and promising source of live biotherapeutics candidates. We examine the composition and functional potential of microbial communities within the reproductive tract, the mechanisms by which they interact with the host, and the emerging evidence supporting the therapeutic applications of vaginally isolated microorganisms. Additionally, we highlight recent advancements in research focused on reproductive tract microbiome, strategies of mining live biotherapeutic product (LBP) candidates, and enlist few potential vaginal origin-LBPs and their associated studies. In addition, this chapter briefly introduces emerging strategies aimed at addressing reproductive health challenges such as vaginal microbiome transplantation (VMT) as innovative tool for addressing persistent challenges in reproductive health.
    Keywords:  Bacterial vaginosis; Lactobacillus species; Live Biotherapeutic Products (LBP); Pre-term birth; Probiotics; Reproductive tract microbiome; Vaginal microbiome transplantation (VMT)
    DOI:  https://doi.org/10.1016/bs.pmbts.2026.01.027
  37. Biol Reprod. 2026 Feb 17. pii: ioag042. [Epub ahead of print]
    A Vaginal Microbiota-Ovary Axis in Chemotherapy-Accelerated Ovarian Aging: Single-Cell Insights into Cellular Dysregulation.
    Shuxin Zhou, Xinfeng Bai, Binqing Xue, Weihua Chu.
       BACKGROUND: Chemotherapy-induced premature ovarian failure (POF) represents a major challenge to female reproductive health, yet the potential regulatory role of vaginal microbiota in this process remains largely unexplored.
    RESULTS: Using a well-established model of chemotherapy-induced ovarian aging, we observed significant disruptions in vaginal microbial ecology characterized by depletion of Lactobacillus species and concomitant enrichment of pathogenic bacteria. Microbiota transplantation effectively reversed these dysbiosis patterns and restored ovarian function. Single-cell transcriptomic analysis revealed that microbial intervention promoted the recovery of granulosa and luteal cell populations while simultaneously suppressing inflammatory activation in ovarian stromal cells, demonstrating the vaginal microbiota's capacity to maintain follicular integrity. Further mechanistic insights showed that microbiota transplantation upregulated key antioxidant defense systems and ribosomal protein networks within ovarian cells, suggesting coordinated actions to mitigate oxidative stress and enhance cellular repair capacity, although the specific microbial metabolites mediating these effects require further elucidation.
    CONCLUSIONS: Our findings establish for the first time the existence of a functional vaginal microbiota-ovary axis and delineate its critical role in protecting against chemotherapy-induced ovarian damage. This work not only advances our fundamental understanding of microbial-endocrine crosstalk but also identifies concrete microbial targets for developing innovative strategies to preserve fertility in cancer patients.
    Keywords:  Chemotherapy; Microbiota transplantation; Ovarian aging; Single-cell RNA sequencing; Vaginal microbiota
    DOI:  https://doi.org/10.1093/biolre/ioag042
  38. J Exp Med. 2026 Apr 06. pii: e20252624. [Epub ahead of print]223(4):
    Sticky memories of an activated macrophage.
    Luca Frosio, Renato Ostuni.
      Innate immune cells can retain molecular imprints of past encounters long after the initial stimulus has ceased. In this issue, Gorin et al. (https://doi.org/10.1084/jem.20250976) reveal an unexpected mechanism by which IFN-γ sustains trained immune states through prolonged signaling driven by cytokine retention at the cell surface.
    DOI:  https://doi.org/10.1084/jem.20252624
  39. Sci Rep. 2026 Feb 18.
    Alternative splicing and differential gene expression during changes in endometrial receptivity in patients with recurrent implantation failure.
    Mao-Li Wang, Bing-Jie Lu, Xiang Lu, Lu Li, Xiao-Xi Sun, Jiu-Cheng Chen, Hu Liu, Chen Chen, Han Wu, Da-Jin Li, Wen-Bi Zhang.
      Recurrent implantation failure (RIF) remains a major challenge in assisted reproductive technology, and the molecular mechanisms underlying endometrial receptivity are incompletely understood. This study aimed to comprehensively characterize transcriptomic alterations, including alternative splicing events (ASEs), differential gene expression (DEGs), and immune cell dynamics across different phases of endometrial receptivity in women with RIF. Endometrial biopsies were collected from 90 healthy fertile controls and 73 RIF patients during pre-receptive, receptive, and post-receptive phases. High-throughput RNA sequencing was performed, and bioinformatic analyses were conducted to identify ASEs, DEGs, immune cell composition, and RNA-binding protein (RBP) networks. Skipped exons and mutually exclusive exons were the predominant splicing events observed. Both ASEs and DEGs were significantly enriched in pathways regulating cell adhesion, cytoskeletal organization, and immune modulation. KHDRBS3 emerged as a potential key RBP involved in splicing regulation during the window of implantation. Immune profiling revealed dynamic alterations in CD8 + T cells, NK cells, and monocytes between non-receptive and receptive phases, suggesting immune dysregulation associated with implantation failure. Drug repurposing analysis identified several small molecules targeting ASE-related genes, offering promising therapeutic options for RIF. These findings highlight the coordinated changes in alternative splicing, gene expression, and immune cell composition that characterize endometrial receptivity and provide insights that may guide the development of novel diagnostic biomarkers and targeted interventions to improve reproductive outcomes.
    Keywords:  Alternative splicing; Differential gene expression; Endometrial receptivity; Immune cells; Recurrent implantation failure
    DOI:  https://doi.org/10.1038/s41598-026-40386-w
  40. Nutr Metab Cardiovasc Dis. 2026 Jan 21. pii: S0939-4753(26)00037-2. [Epub ahead of print] 104575
    Sex differences in the longitudinal association between metabolomic biomarkers and carotid artery plaques.
    Sabah Rehman, Eric Moses, Terence Dwyer, Alison Venn, Seana Gall.
       BACKGROUND AND AIMS: The development of carotid artery atherosclerosis differs between men and women. We examined the role of the metabolome in these sex differences in Australian adults.
    METHODS AND RESULTS: Data is from the Australian Childhood Determinants of Adult Health (CDAH) study where 73 metabolomic biomarkers were measured at ages 26-36 years (2004-06) and carotid artery plaques were measured at ages 36-46 years (2014-19). We identified metabolites that modified the effect of sex on plaques in log-binomial regression models. Sex-specific regressions were performed for metabolic biomarkers that had a sex-specific association with plaques. There were 638 participants (53 % women, mean [SD] age 31.2 [2.6] years) in the analysis. Interactions were significant for sex with omega-3 fatty acid, docosahexaenoic acid (DHA), saturated fat percentage, and albumin on their association with plaques. Inverse associations with plaques in women, but not men, were found for saturated fat percentage in adjusted analysis (RR/SD increase 0.52 95 % CI 0.36-0.79; p < 0.001). Albumin signal area was positively associated with plaques in women in adjusted analysis (RR/SD increase 1.56 95 % CI 1.33-2.15; p = 0.006).
    CONCLUSION: Associations between metabolic biomarkers and plaques were different in women compared with men, which may reveal sex-specific factors for atherosclerosis in women.
    Keywords:  Carotid plaques; Metabolomic biomarkers; Sex differences
    DOI:  https://doi.org/10.1016/j.numecd.2026.104575
  41. Andrology. 2026 Feb 20. e70194
    Impact of Pre-treatment Testosterone Levels on Severity of Adverse Effects in Men on Androgen Deprivation Therapy for Prostate Cancer.
    Milena Braga, Thomas G Travison, Mary-Ellen Taplin, Daniel Habtemariam, Alyssa B Dufour, Marie McDonnell, Donald C Simonson, Alexander P Lin, Elizabeth Borwick, Leila Chammas, Hussein Kafel, Praful Ravi, Adam S Kibel, Paul L Nguyen, Thomas Storer, Shehzad Basaria.
       BACKGROUND: Men undergoing androgen deprivation therapy (ADT) for prostate cancer experience various adverse effects. Those with higher pre-treatment testosterone levels often express concerns about experiencing increased severity of these side effects, but this association has not been studied previously.
    OBJECTIVES: The aim of this study was to assess the association of pre-treatment testosterone levels with changes in body composition, physical function, sexual function, and energy in men undergoing 24 weeks of ADT.
    MATERIALS AND METHODS: Thirty-nine men were assessed at baseline and after 24 weeks of ADT. Body composition was assessed using dual-energy x-ray absorptiometry. Energy and vitality were evaluated using the Hypogonadism Energy Diary, and sexual function was assessed using the Sexual Arousal, Interest, and Drive scale. Physical function was assessed using the PF-10 subscale of the Short Form-36 Health Survey. Total and free testosterone levels were measured using liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. The association between pre-treatment testosterone levels and variables of interest was tested using linear regression analysis.
    RESULTS AND DISCUSSION: At 24 weeks, the mean serum total testosterone level declined from 471 ± 157 to 7.7 ± 4.5 ng/dL, total fat mass increased by 3.7 kg (p < 0.0001), and total lean mass decreased by 2.2 kg (p < 0.0001). Participants experienced a decline in physical function, overall energy, and sexual desire. Pre-treatment testosterone levels were not associated with the magnitude of worsening in any of these outcomes.
    CONCLUSION: Severity of adverse effects of ADT is not influenced by pre-treatment testosterone levels. This finding allows clinicians and patients to make informed decisions regarding treatment.
    Keywords:  androgen deprivation therapy; body composition; energy; physical function; quality of life; sexual function
    DOI:  https://doi.org/10.1111/andr.70194
  42. Front Immunol. 2025 ;16 1699362
    Sex-specific differences in abscopal responses to combined radiotherapy and immune checkpoint inhibition-insights from a multicenter study.
    Maike Trommer, Alexander Rühle, Felix Ehret, Allison Lamrani, Charlotte Schmitter, Justus Kaufmann, Matthias Mäurer, Georg Wurschi, Ping Jiang, Andrea Baehr, Annika Hardt, Raphael Bodensohn, Lukas Käsmann, Maria Waltenberger, Eleni Gkika, Davide Scafa, Julian P Layer, Esther G C Troost, Sally A Elkhamisy, Danny Jazmati, Ilinca Popp, Sebastian Neppl, Anna Hagemeier, Angela Besserer, Simone Ferdinandus.
       Purpose: Abscopal effects (AbE) during combined radiotherapy (RT) and immune checkpoint inhibition (ICI) represent a potential mechanism for systemic tumor control, yet sex-specific differences in these responses remain largely unexplored. We investigated sex-associated signals in outcomes of combined RT-ICI in a multicenter cohort. We analyzed the incidence of AbE and survival outcomes with respect to clinical and biomedical markers.
    Methods: In this observational multicenter study, patients with metastatic solid tumors receiving RT-ICI and showing at least one non-irradiated lesion (NIL), assessed using iRECIST criteria, were analyzed. Abscopal response (AR) was defined as ≥30% reduction in NIL size, abscopal progression (AP) as ≥20% increase, and abscopal control (AC) as changes within this range.
    Results: Among 3,773 screened patients, 142 met the inclusion criteria (62% male, median age 62 years; 38% female, median age 58 years). AR and AC occurred more frequently in females (24% vs. 14%, 35% vs. 31%). While OS showed no significant difference (p=0.81), Cox regression analyses revealed significant associations of a longer ICI-to-RT-interval (males: HR = 0.903 [0.833-0.978], p=0.012; females: HR = 0.748 [0.621-0.900], p=0.002) and a BMI ≥25 kg/m² with survival in both sexes (males: HR = 4.282 [1.473-12.446], p=0.008; females: HR = 4.801 [1.182-19.502], p=0.028 with survival in both sexes). Elevated C-reactive protein (CRP) (≥5 mg/L) showed prognostic significance only in males (HR = 4.764 [1.184-19.170], p=0.028).
    Conclusion: Our findings suggest the possibility of sex-specific patterns in AbE occurrence. Additionally, our analyses identified sex-associated prognostic factors, including the importance of ICI-to-RT interval and BMI in both sexes and the male-specific prognostic value of CRP. These observations warrant further research and consideration in designing personalized RT-ICI combination strategies.
    Keywords:  abscopal effects; immune checkpoint inhibition; radioimmunotherapy; sex-specific immune effects; sex-specific radiation oncology
    DOI:  https://doi.org/10.3389/fimmu.2025.1699362
  43. Front Immunol. 2026 ;17 1715880
    Decoupling of maternal and neonatal inflammatory levels at the maternal-fetal interface: evidence from a population-based proteomic study.
    Floriana Milazzo, Frederieke Gigase, Anna Suleri, Bushra Amreen, Darwin D'Souza, Seunghee Kim-Schulze, Veerle Bergink, Lot de Witte, Corina Lesseur, Anna-Sophie Rommel.
       Background: Maternal inflammation during pregnancy has been linked to offspring physical and neurodevelopmental health. This association has been hypothesized to operate through fetal immune responses. Yet, population-based evidence exploring the relationship between maternal and neonatal inflammation remains limited. This study investigates the associations of maternal inflammatory markers measured in the third trimester and at birth with neonatal inflammatory profiles at birth.
    Methods: Interleukin (IL)-1β, IL-6, IL-17a (pg/mL), and CRP (mg/L) levels were measured in maternal plasma at birth and in the third trimester and standardized for the at-birth and third-trimester subset. In the neonates, 92 inflammatory markers were measured in Dried Blood Spots using Olink®. We used linear regression models with empirical Bayes moderation to investigate the association between maternal inflammatory marker levels at each timepoint and neonatal inflammatory marker levels. We adjusted for maternal factors, child factors, and technical factors. We applied the false discovery rate (FDR-adjusted p-value <0.05) to adjust results for multiple comparisons.
    Results: Maternal IL-1β, IL-6, IL-17a, and CRP levels measured at birth (n=194 mother-child dyads) or in the third trimester (n=235) were not significantly associated with levels of any of the 92 neonatal inflammatory markers. Effect estimates were small, and no associations survived FDR correction (FDR <0.05). Findings were observed with robust parsimonious adjustment for covariates and were similar across both maternal sampling timepoints.
    Conclusion: Maternal inflammation measured at birth and in the third trimester was not significantly associated with widespread changes in neonatal peripheral inflammatory profiles. These findings suggest that low-grade maternal inflammation may not elicit detectable systemic inflammatory responses in neonates at birth in a general population sample. Future research should replicate our findings and assess the role of neonatal inflammatory markers in subsequent offspring health outcomes.
    Keywords:  maternal immune activation; maternal-fetal immune regulation; neonatal inflammation; perinatal immune system; pregnancy
    DOI:  https://doi.org/10.3389/fimmu.2026.1715880
  44. J Cachexia Sarcopenia Muscle. 2026 Feb;17(1): e70232
    Menopause, Female Sex Hormones, Skeletal Muscle Mass and Muscle Protein Turnover in Humans.
    Campbell Menzies, Richard Bowtell, Natalie Shur, Matthew S Brook.
      Sarcopenia describes the loss of muscle mass and function with age. The increase in prevalence of sarcopenia in women appears to coincide with the onset of menopause, which is characterized by large changes to the hormonal milieu such as decreased oestrogen and progesterone concentrations. Although the timing of menopause and sarcopenia may coincide, there is a lack of high-quality evidence demonstrating a link between the two. This narrative review aims to assess evidence for the effects of menopause on muscle mass and muscle protein turnover. Longitudinal (n = 4/5) and cross-sectional (n = 7/11) studies demonstrate a reduction in lean or muscle mass across the menopausal transition with -2.5% and -5.7% reductions in perimenopausal and postmenopausal women, respectively, compared to premenopausal women. Most of this evidence (n = 10/11) is taken through assessment of lean body mass via dual-energy x-ray absorptiometry (DXA), which may underestimate changes in muscle mass. Assessment on changes to muscle protein turnover is largely limited to short-term measures of muscle protein synthesis (MPS), which may be elevated in older women versus younger women (n = 3/7) or age-matched males (n = 4/5). MPS responses to anabolic stimuli, such as resistance exercise (n = 3/4) or protein ingestion (n = 3/6), may be blunted in older women. Evidence assessing muscle protein breakdown (MPB) is lacking; however, evidence from animal and cell models demonstrates the role of estradiol in suppressing MPB, which may contribute to an increase in MPB following menopause. Advancements in understanding the role of the menopausal transition in the regulation of muscle mass, and subsequent effectiveness of interventions such as exercise or exogenous hormone provision will enable healthy ageing and sarcopenia prevention in older women.
    Keywords:  ageing; menopause; muscle mass; protein turnover; resistance exercise; sarcopenia
    DOI:  https://doi.org/10.1002/jcsm.70232
  45. Front Endocrinol (Lausanne). 2026 ;17 1726339
    Age-related mitochondrial energy metabolism reprogramming occurs in granulosa cells during ovarian aging.
    Mengyu Shi, Zhicheng Jia, Xinxin Yang, Wenlong Qi, Xinwei Sun, Yongqian Li, Peixuan Wang, Ying Guo.
       Objective: Ovarian aging is an inevitable age-associated biological phenomenon.Enhancing clinical pregnancy outcomes in women with advanced maternal age (AMA) has emerged as a critical research priority in reproductive medicine. The current study seeks to unravel the mechanism governing mitochondrial energy metabolism reprogramming in granulosa cells (GCs) during age-associated ovarian aging.
    Methods: We conducted an age-stratified prospective observational study involving GC samples from 10 young infertile women (young group: 21-34 years) and 10 infertile women with AMA (AMA group: 35-42 years), all undergoing in vitro fertilization-embryo transfer (IVF-ET). Participants were recruited from November 2023 to November 2024. Additionally, an in vitro oxidative stress-induced senescence model was established using hydrogen peroxide (H2O2)-treated human ovarian granulosa-like tumor cell line (KGN cells) to further investigate metabolic disturbances and mitochondrial reactive oxygen species (mtROS) levels in senescent GCs.
    Results: High-resolution targeted metabolomics revealed 25 statistically significant metabolite alterations in ovarian GCs, indicating profound dysregulation of core energy metabolism pathways-particularly oxidative phosphorylation (OXPHOS), glycolysis, and the tricarboxylic acid (TCA) cycle. Compared to the young group, the AMA group exhibited upregulated glycolytic metabolites alongside downregulated OXPHOS and TCA cycle intermediates. These findings were further validated in an H2O2-induced KGN cells senescence model, where treated cells demonstrated: (1) increased senescence-associated β-galactosidase (SA-β-gal) activity, (2) elevated extracellular acidification rate (ECAR) and lactate (Lac) production, (3) reduced oxygen consumption rate (OCR), (4) depleted glucose and pyruvate(Pyr) pools, and (5) heightened mtROS generation relative to control group.
    Conclusions: Collectively, our research demonstrates that GCs undergo mitochondrial energy metabolism reprogramming, characterized by a metabolic shift from OXPHOS to glycolysis, during ovarian aging. These observations suggest that age-associated glycometabolic perturbations may represent a novel therapeutic target for infertility in women with AMA.
    Keywords:  KGN cells; female infertility; granulosa cells; mitochondrial energy metabolism reprogramming; ovarian aging
    DOI:  https://doi.org/10.3389/fendo.2026.1726339
  46. Clin Chem Lab Med. 2026 Feb 17.
    Age- and sex-specific reference intervals for 11-oxygenated androgens from infancy throughout childhood and adulthood.
    Robert Zeidler, Friederike Wagner, Uta Ceglarek, Wieland Kiess, Jürgen Kratzsch, Ronny Baber, Kerstin Wirkner, Berend Isermann, Alexander Gaudl, Mandy Vogel, Ronald Biemann.
       OBJECTIVES: The adrenal glands are the main source of 11-oxygenated androgens (11-OAs), including the potent 11-ketotestosterone (11-KT) and the weaker metabolites 11β-hydroxyandrostenedione (11-OHA4), 11β-hydroxytestosterone (11-OHT) and 11-ketoandrostenedione (11-KA4). Due to their adrenal origin, 11-OAs allow the differentiation of adrenal and extra-adrenal-produced androgens. However, their clinical use is limited due to the lack of robust age- and sex-specific reference intervals (RIs).
    METHODS: To establish RIs from infancy throughout childhood and adulthood, we performed simultaneous quantification of 11-OHA4, 11-OHT, 11-KA4, 11-KT, and clinically relevant steroid hormones via LC-MS/MS. We analyzed 3,796 serum samples from 2,505 healthy individuals, aged 0.25-80 years, encompassing minipuberty and pubertal stages.
    RESULTS: 11-OA serum levels increase from infancy throughout childhood and adulthood, with the most pronounced increase during puberty. Significant sex differences were observed, and age-, sex-, and puberty-dependent RIs were established. In contrast to testosterone, 11-OAs exhibited a comparable pattern during the first year of life in both sexes. At 3 and 6 months of age - when testosterone levels were 100- and 10-fold higher, respectively, in males than in females - no correlation was observed between testosterone and the adrenal-derived androgens (11-OAs, A4, and DHEAS) in males.
    CONCLUSIONS: Established age-, sex-, and puberty-dependent RIs support the clinical interpretation of 11-OA measurements in disorders characterized by androgen excess. The differences in the regulation of classical androgens and 11-OAs during minipuberty suggest that the transient increase in androgens during the first months of life is most likely due to activation of the hypothalamic-pituitary-gonadal axis.
    Keywords:  11-oxygenated androgens; androgens; minipuberty; puberty; reference intervals; steroid hormones
    DOI:  https://doi.org/10.1515/cclm-2025-1440
  47. Sci Rep. 2026 Feb 18.
    Androgen dysregulates the follicular extracellular matrix and increases pro-fibrotic gene expression in the mouse ovary.
    Thomas I R Hopkins, Avigdor Lerner, Iain E Dunlop, Stephen Franks, Kate Hardy.
      The extracellular matrix (ECM) defines the biomechanical and biochemical microenvironment of tissues, directing cell behaviour and phenotype. In the ovary, ECM must dynamically remodel in each cycle under hormonal regulation to control follicle development and produce fertilizable oocytes. Dysregulation of this process may result in aberrant formation of ECM as seen in polycystic ovary syndrome (PCOS) whose pathology includes fibrosis of the ovary and which is a major cause of infertility. PCOS is characterised by hyperandrogenism and, here, we investigate the impact of androgens on fibrosis, cell-ECM interactions and mechanosensing. We report an altered network of gene expression related to the genesis of fibrosis. Preantral follicles from C57BL/6 mice (14-15 days postpartum) were stimulated with dihydrotestosterone (DHT, 10nM) in 24/72 hours culture. Expression of fibrosis-associated genes (Eln; Ctgf; Acta2; Plod2; Hpse) significantly increased with androgen (72 h), as did TGF-β signalling (Tgfb1; Tgfb3). We show a direct connection between androgen and mechanosensing within the ovary, with androgen upregulating the mechanosensitive Hippo pathway (Yap1; Lats1; Lats2; Stk3; Stk4; Frmd6) and downstream targets (Ctgf; Axl; Cyr61). Our results highlight hyperandrogenism as a probable driver of the fibrosis in the polycystic ovary, and emphasise the importance of ECM regulation in follicle development and fertility.
    Keywords:  Androgen; ECM; Fibrosis; Ovary; PCOS
    DOI:  https://doi.org/10.1038/s41598-025-32927-6
  48. Reprod Dev Med. 2026 Mar;10(1): 1-14
    Uterine epithelial estrogen receptor α temporally regulates preimplantation uterine immunity involving interleukin-1β signaling.
    Jonathan Matthew Hancock, Taylor Elijah Martin, Yuehuan Li, Skyler Owens-Gonzalez, Tong Zhou, Declan James Gresham, Wendy Tharpe Watford, Xiaoqin Ye.
       Objective: Estrogen receptor α (ERα/Esr1) is essential for uterine function during early pregnancy. The uterus has a dynamic immune environment, including transient endometrial inflammation in response to post-coital semen. The uterine epithelium is the first contact for uterine lumen contents (e.g., semen). We aimed to determine the function and mechanism of uterine epithelial ERα in regulating the uterine immune response to semen.
    Methods: Uterine tissues and uterine flushes were collected from naturally mated uterine epithelial ERα-deficient epiERα -/- (Esr1 f/- Wnt7a Cre/+ ) mice and Esr1 f/- control mice on day 0.5 post-coitus (D0.5) and D3.5. Histology, immunohistochemistry, mRNA-seq, real-time polymerase chain reaction (PCR), flow cytometry, and cytokine assays were employed to determine the spatiotemporal distribution of immune cells and assess their functional states.
    Results: There was a sharp decline in neutrophils from D0.5 to D3.5 in both Esr1 f/- and epiERα -/- uteri. Immunohistochemistry detected ~7-fold ELANE+ neutrophils in the uterine luminal epithelium (LE) layer and ~1.5-fold in the stromal layer of D0.5 epiERα -/- uterus compared to D0.5 Esr1 f/- counterparts. Gelled uterine lumen contents with varied densities of neutrophils and sperm were detected in both D0.5 Esr1 f/- and epiERα -/- mice. Flow cytometry revealed significantly increased percentages of neutrophils among CD45+ leukocytes in uterine digests with a trend of increased neutrophil cell number and proportions in uterine flushes from D0.5 epiERα -/- mice. Dysregulation of immune genes at both mRNA and protein levels was noted in D0.5 epiERα -/- LE/uterus, especially an upregulation of inflammatory cytokines. In particular, upregulation of genes involved in signaling by interleukin (IL)-1β, a potent pro-inflammatory cytokine involved in mating-induced uterine inflammation, was observed in both the uterine tissue and uterine flush.
    Conclusion: These findings demonstrate an essential function of uterine epithelial ERα in controlling mating-induced inflammation in the LE layer, stromal layer, and uterine lumen, and highlight the IL-1β signaling pathway among the molecular mechanisms involved in regulation of uterine inflammation by uterine epithelial ERα.
    Keywords:  Early pregnancy; IL-1β Signaling; Inflammation; Neutrophil; Uterine epithelial ERα
    DOI:  https://doi.org/10.1097/RD9.0000000000000149
  49. Psychoneuroendocrinology. 2026 Feb 13. pii: S0306-4530(26)00057-0. [Epub ahead of print]187 107797
    Hormonal changes, stable attention: Gender-affirming hormone treatment does not alter selective attention to infant cues in transgender individuals.
    Alina von Klitzing, Esther Diekhof, Peer Briken, Johanna Schröder, Sarah Holtfrerich, Johannes Fuss.
      Testosterone is known to modulate parental caretaking and responses to infant cues. Recent evidence suggests a negative association between testosterone and selective attention towards baby schema. Transgender people undergoing gender-affirming hormone therapy (GAHT) experience substantial changes in testosterone levels and they often have or want to have children, highlighting the need to determine whether GAHT changes responsivity to infant cues. In the present pre-registered study, we analyzed whether transgender participants undergoing GAHT exhibit a change in selective attention toward baby schema in a controlled trial (N = 98; mean age = 28.57 years). To this end, we used a computer-based target detection paradigm consisting of infant and adult human images that has been used to demonstrate baby schema effects in relation to testosterone levels. Our results indicate that six months of GAHT had no observable effect on selective attention toward baby schema in our transgender participants. The association between selective attention toward baby schema and testosterone, which has so far only been demonstrated based on endogenous hormone levels, does not appear to be transferable to transgender people, who alter their testosterone levels through GAHT. Our findings extend previous findings by providing insights on previously unexplored effects of GAHT on the attentional system.
    Keywords:  Baby schema; Gender-affirming hormone therapy; Selective attention; Target detection task; Testosterone; Transgender
    DOI:  https://doi.org/10.1016/j.psyneuen.2026.107797
  50. Sci Rep. 2026 Feb 16.
    Fetal sex-specific differences in the placental transcriptome of gestational diabetes.
    Lydia L Shook, Frédérique White, Kalpana D Acharya, Sofía Torres-Bigio, Laura Ibanez-Pintor, Daehee Han, François Aguet, Kristin G Ardlie, Jose C Florez, Luigi Bouchard, Pierre-Étienne Jacques, S Ananth Karumanchi, Camille E Powe, Marie-France Hivert, Andrea G Edlow.
      
    Keywords:  Gestational diabetes mellitus; Placenta; Pregnancy; Sex as a biological variable; Sexual dimorphism; Transcriptomics
    DOI:  https://doi.org/10.1038/s41598-026-39975-6
  51. Transl Psychiatry. 2026 Feb 18.
    Selective estrogen receptor modifiers on the antidepressant-like effects of electroconvulsive seizures in adolescent rats.
    Celia Garau, Sandra Ledesma-Corvi, Yaiza Jiménez-Marín, Rubén García-Cabrerizo, M Julia García-Fuster.
      During the past decade, our group has induced electroconvulsive seizures (ECS) in rodent models of early-life stress to prove clear differences in antidepressant-like efficacy mainly driven by sex and age, with females and adolescents showing diminished responses (as opposed to males and adult rodents). Moreover, we have proven a role for sex hormones in this response, since letrozole, an inhibitor of the biosynthesis of estrogens, improved the antidepressant-like efficacy of ECS in adolescent female rats. In this follow-up study, we utilized selective estrogen receptor modifiers (tamoxifen and clomiphene) to evaluate how they interact with the antidepressant-like response induced by ECS in male and female adolescent rats. Early-life stressed Sprague-Dawley rats through maternal separation were treated during adolescence with tamoxifen (1 mg/kg, 7 days) or clomiphene (10 mg/kg, 5 days) and/or with ECS (95 mA, 0.6 s, 100 Hz, 1 session/day, 5 days). Antidepressant-like responses were measured behaviorally under the stress of the forced-swim test, and through hippocampal markers (cell proliferation and neurogenic differentiation, and BDNF protein level). The main results proved that tamoxifen improved the expected antidepressant-like response of ECS in adolescent rats, as observed in the forced-swim test, while boosted hippocampal proliferation and neurogenic differentiation. Contrarily, clomiphene did not alter ECS' response at the behavioral level and even showed some negative signs on the neuroplasticity markers evaluated (decreased neurogenic differentiation and BDNF content). Therefore, when considering an estrogen receptor modifier to enhance the antidepressant-like potential of ECS in adolescence, tamoxifen emerges as a promising option due to its positive behavioral and neuroplastic effects.
    DOI:  https://doi.org/10.1038/s41398-026-03909-7
  52. Front Cell Infect Microbiol. 2025 ;15 1730739
    Gut microbiota as a key regulator in endometriosis: mechanisms, therapeutic opportunities, and future perspectives.
    Xiaojun Liu, Minghui Fan, Yang Wang, Dongyun He, Li Liu.
      Endometriosis (EMs), a common and frequently occurring gynecological disease, is a major cause of chronic pelvic pain and infertility in women. Its pathogenesis remains unclear to date, and it is characterized by high invasiveness and recurrence tendency. Although the specific pathogenesis of EMs has not been clarified, existing studies have confirmed that gut microbiota dysbiosis plays an important role in its pathogenic process. Studies suggest that gut microbiota may affect the occurrence and progression of EMs through immunoinflammatory pathways and metabolic pathways (such as enhanced estrogen metabolism and abnormal lipid metabolism). Meanwhile, approaches including dietary intervention, supplementation of probiotics or prebiotics, and microbiota transplantation can help prevent and alleviate EMs symptoms, providing potential therapeutic methods. This article will review the research progress on the correlation between gut microbiota dysbiosis and EMs, with the aim of offering more references for the diagnosis and treatment of EMs.
    Keywords:  endometriosis; estrogen metabolism; gut microbiota; inflammation; probiotics
    DOI:  https://doi.org/10.3389/fcimb.2025.1730739
  53. Arch Gynecol Obstet. 2026 Feb 15. 313(1): 97
    Correlation of blood lipid levels with the severity of polycystic ovary syndrome and its predictive value for pregnancy outcome.
    Dongting Mao, Yanan Wei, Chengcheng Wang, Jing Tao.
       OBJECTIVE: To analyze the correlation between lipid levels and the severity of polycystic ovary syndrome (PCOS) and its predictive value for pregnancy outcome.
    METHODS: This retrospective study included 275 PCOS patients treated with ovulation induction therapy and 234 healthy controls (used only for baseline comparisons). Lipid levels were correlated with disease phenotype and sex hormones using Spearman/Pearson coefficients. Binary logistic regression and ROC curves assessed the predictive value of lipid levels for pregnancy failure.
    RESULTS: There were statistically significant differences between the two groups in glycemic indexes (fasting blood glucose (FBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR)) and sex hormone indexes (testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), anti-Müllerian hormone (AMH)). The levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) were significantly elevated in patients with PCOS and were closely correlated with the severity of the disease. In addition, these four lipid parameters were significantly positively correlated with T, LH, FSH, and AMH, and significantly negatively correlated with E2. Elevated levels of T, LH, TG, LDL-C, and Apo B were independent risk factors for pregnancy failure after ovulation induction treatment. TG assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.861 (sensitivity 75.61%, specificity 85.53%); LDL-C assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.868 (sensitivity 75.61%, specificity 83.55%); and Apo B assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.836 (sensitivity 74.80%, specificity 86.84%).
    CONCLUSION: Lipid levels were significantly correlated with the severity of disease in PCOS patients, and TG, LDL-C, and Apo B levels assisted in predicting the occurrence of pregnancy failure after ovulation induction therapy.
    Keywords:  Blood lipids; Glycemic index; Ovulation induction therapy; Polycystic ovary syndrome; Pregnancy outcome; Sex hormone index
    DOI:  https://doi.org/10.1007/s00404-026-08344-z
  54. Front Microbiol. 2025 ;16 1703708
    Sex-specific effects of fecal microbiota transplantation on TBI-exacerbated Alzheimer's disease pathology in mice.
    Sirena Soriano, Austin Marshall, Morgan Holcomb, Hannah Flinn, Marissa Burke, Göknur Kara, Paula Scalzo, Sonia Villapol.
       Background: Traumatic brain injury (TBI) accelerates Alzheimer's disease (AD) pathology and neuroinflammation, potentially via gut-brain axis disruptions. Whether restoring gut microbial homeostasis mitigates TBI-exacerbated AD features remains unclear, particularly with respect to sex differences.
    Objective: The goal of our study was to test whether fecal microbiota transplantation (FMT) modifies amyloid pathology, neuroinflammation, gut microbial composition, metabolites, and motor outcomes in male and female 5xFAD mice subjected to TBI.
    Methods: Male and female 5xFAD mice received sham treatments or controlled cortical impact, followed 24 h later by vehicle (VH) or sex-matched FMT from C57BL/6 donors. Assessments at baseline, 1-, and 3-days post-injury (dpi) included Thioflavin-S and 6E10 immunostaining for Aβ, Iba-1 and GFAP for glial activation, lesion volume, rotarod performance, 16S rRNA sequencing for microbiome profiling, serum short-chain fatty acids (SCFAs), and gut histology.
    Results: TBI increased cortical and dentate gyrus Aβ burden, with females showing greater vulnerability. FMT reduced Aβ deposition in sham animals and shifted plaque morphology but did not attenuate TBI-induced amyloid escalation. FMT differentially modulated glial responses by sex and region (reduced microgliosis in males) without altering lesion volume at 3 dpi. Rotarod performance was better in sham females compared to males and declined in FMT-treated TBI females. Fecal microbiome alpha diversity and richness were unchanged, while beta diversity revealed marked, time-dependent community shifts after TBI that were slightly altered by FMT. Gut morphology remained broadly intact, but crypt width increased after TBI, particularly in males.
    Conclusion: In 5xFAD mice, TBI drives sex-dependent worsening of amyloid pathology, neuroinflammation, and dysbiosis. Acute FMT partially restores microbial composition and plaque features in sham animals but fails to reverse TBI-induced neuroinflammation or motor deficits. These findings underscore the context- and sex-dependence of microbiome interventions and support longer-term, sex-specific strategies for AD with comorbid TBI.
    Keywords:  Alzheimer’s disease; fecal microbiota transplantation; gut-brain axis; microbiome; neuroinflammation; sex differences; short-chain fatty acids; traumatic brain injury
    DOI:  https://doi.org/10.3389/fmicb.2025.1703708
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