bims-simsho Biomed News
on Systems immunology and sex hormones
Issue of 2025–12–07
thirty-six papers selected by
Chun-Chi Chang, Lunds universitet
  1. Targeting androgen receptor signaling to enhance cancer immunotherapy.
  2. Gonadal hormones contribute to sex differences in behavior, pathology and epigenetic modifications in the 3×Tg-AD mouse model of Alzheimer's disease.
  3. Androgen Signaling in ILC2s Drives Sex Differences in Helicobacter-Induced Gastric Inflammation and Atrophy.
  4. The hypothalamic effects of PACAP on the hypothalamic-pituitary-gonadal axis in male mice.
  5. Robust antibody and T cell responses tracked longitudinally in patients with long COVID.
  6. Sex-dimorphic reprogramming of fetal mouse brain development by maternal estradiol excess.
  7. Transcriptional coregulator ZMIZ1 modulates estrogen responses that are essential for healthy endometrial function.
  8. Androgen receptor splice variant expression and prostate cancer recurrence after salvage therapy.
  9. Sex differences in gene regulation and its impact on cancer incidence.
  10. Sex-Specific Associations of Prolactin and Progesterone With Glycemic Control in Adults With Type 1 Diabetes.
  11. New insights into sexual dimorphism in cardiometabolic health.
  12. STARD4 suppresses tumorigenesis and attenuates enzalutamide resistance via lipid metabolic reprogramming and AR stabilization in prostate cancer.
  13. The interplay of estrogen, gut microbiome, and bone immunity in osteoporosis.
  14. Serum cholic acid and cecal Faecalibaculum increase in a male-specific manner in a murine hepatocellular carcinoma model.
  15. Sexually dimorphic role of estrogen receptor α in preserving right ventricular endothelial integrity.
  16. Microbiota insights in endometriosis.
  17. Lactylation at the crossroads of immune metabolism and epigenetic regulation: revealing its role in rheumatic immune diseases.
  18. Effect of probiotic-derived metabolites on hormonal and metabolic profiles in women with polycystic ovary syndrome: a systematic review and meta-analysis.
  19. The Utility of Serum Free Testosterone Concentrations in Monitoring Gender-Affirming Testosterone Therapy in Transmasculine Youth with Obesity.
  20. Sex-Specific Molecular Architecture of Microglia-Mediated Neuronal Pruning Across the Human Lifespan.
  21. Dual Salmonella vaccination attenuates microbiota dysbiosis and enhances microbiota functionality in poultry challenged with S. Typhimurium.
  22. Evaluation of donor's hormonal profile according to sex and age.
  23. Perinatal citalopram exposure alters the gut composition and microbial metabolic profiles of Sprague-Dawley rat dams and female offspring but not male offspring.
  24. Biological sex as a variable in immunity does not affect parabolic flight-induced alterations in immune responses.
  25. Females with Obesity Exhibit Greater Influenza Vaccine-induced Immunity and Protection than Males in a Mouse Model.
  26. Sex-specific gut microbiome dynamics in Labeo catla: links to reproductive hormones, metabolic dimorphism, and environmental factors.
  27. TGFBR2 coordinates the endometrial response to estrogen, regulating endometrial hyperplasia and fertility.
  28. A visualization tool for individual gene expression profiles among males and females in GTEx tissues.
  29. Sex differences in antibody responses to influenza A/H3N2 across the life course.
  30. The impact of androgen deprivation therapy and novel hormonal therapy on thyroid hormone levels in prostate cancer patients: a systematic review and meta-analysis.
  31. Effect of improvement in the endometrial microbiome on in vitro fertilization outcomes.
  32. Deslorelin influences canine epididymal gene expression of the androgen receptor and prostaglandin metabolism.
  33. Prenatal maternal salivary hormones and timing of tooth eruption in early childhood: a prospective birth cohort study.
  34. Large-scale characterisation of the nasal microbiome redefines Staphylococcus aureus colonisation status.
  35. Cervicovaginal microbiome composition and absolute quantity are associated with pelvic inflammatory disease.
  36. Lipid Metabolic Disorders in Neurodegenerative Diseases - Role of Androgen Receptor.
  1. Trends Pharmacol Sci. 2025 Dec 03. pii: S0165-6147(25)00257-3. [Epub ahead of print]
    Targeting androgen receptor signaling to enhance cancer immunotherapy.
    David A Bader, Binita Chakraborty, Donald P McDonnell, Matthew D Hirschey.
      Men experience higher cancer incidence and mortality than women, and accumulating evidence implicates androgen receptor (AR) signaling as a key biological driver of these sex-based disparities. AR signaling can suppress adaptive anticancer immunity. Preclinical studies across multiple cancer types show that AR inhibition enhances T cell function and sensitizes tumors to immune checkpoint inhibition. However, recent Phase 3 trials combining AR suppression with immune checkpoint blockade in prostate cancer (PCa) failed to demonstrate clinical benefit. We discuss these developments and summarize recent studies defining the role of AR signaling in anticancer immunity. We propose strategies to translate emerging insights into rational trial designs that optimize the integration of AR suppression with immunotherapy.
    Keywords:  androgen deprivation therapy; androgen receptor; cancer immunotherapy; immune checkpoint blockade; sex-based differences in cancer; tumor immune microenvironment
    DOI:  https://doi.org/10.1016/j.tips.2025.11.003
  2. Biol Sex Differ. 2025 Dec 01.
    Gonadal hormones contribute to sex differences in behavior, pathology and epigenetic modifications in the 3×Tg-AD mouse model of Alzheimer's disease.
    Wei Song, Samantha D Creighton, Bernadeta Michalski, Juliette Mojgani, Minesh Kapadia, Donglai Ma, Boris Sakic, Iva B Zovkic, Margaret Fahnestock.
       BACKGROUND: Sex-dependent differences in prevalence and severity are characteristics of Alzheimer's disease (AD). Using the 3×Tg-AD mouse model, we previously reported that adult males show early behavioral dysfunction, altered epigenetic factors and lack of plaque/tangle pathology. Conversely, adult females retain more severe AD-like pathology and behavior. The present study examines whether gonadal hormones play a role in these differences in current cohorts of 3×Tg-AD mice.
    METHODS: 3×Tg-AD and wild-type mice were gonadectomized or sham-operated at 3 months of age. After behavioral phenotyping at 6 months of age, the animals were assessed for molecular markers of AD pathology and expression of genes and histone variants associated with neurodegeneration.
    RESULTS: In female transgenic (AD) mice, gonadectomy resulted in poorer spatial learning performance. In contrast, in transgenic male animals, gonadectomy improved spatial learning and memory. Compared to sham-operated AD females, gonadectomized AD females exhibited enhanced expression of mouse (m) Mapt and App genes, consistent with reduced binding activity of the repressive histone variant macroH2A1 at the mMapt gene, but there was no effect on Aβ42 or pTau181 levels. In contrast, gonadectomized AD males showed significantly increased macroH2A1 binding at the mPsen1 promoter, reduced expression of the App and MacroH2A1 genes, and reduced cortical soluble Aβ42 levels compared to sham-operated AD males.
    CONCLUSIONS: In sum, the results suggest that reduction in serum levels of female gonadal hormones impairs spatial learning capacity, whereas loss of male gonadal hormones enhances spatial learning and memory. In females, gonadectomy reduces binding of the repressive histone variant MacroH2A1 to the mouse Mapt gene and increases expression of the mouse App and Mapt genes without affecting Aβ42 or pTau181 levels. Conversely, loss of male gonadal hormones increases binding of MacroH2A1 to the mouse Psen1 gene and decreases App expression and Aβ42 levels but has no effect on tau expression. Our work suggests that adult gonadal hormones contribute to sex differences in AD-like pathology and performance in learning and memory tasks. Moreover, sex-specific differences in AD-like pathology are partially due to the action of histone variants associated with neurodegeneration, such as macroH2A1.
    Keywords:  3×Tg-AD mice; Alzheimer’s disease; Gonadectomy; Histone variants; MacroH2A1; Sexual dimorphism
    DOI:  https://doi.org/10.1186/s13293-025-00790-9
  3. Cell Mol Gastroenterol Hepatol. 2025 Nov 28. pii: S2352-345X(25)00231-0. [Epub ahead of print] 101690
    Androgen Signaling in ILC2s Drives Sex Differences in Helicobacter-Induced Gastric Inflammation and Atrophy.
    Benjamin C Duncan, Maeve T Morris, Jordan L Pascoe, Stuti Khadka, Lei Wang, Gangqing Hu, Jonathan T Busada.
       BACKGROUND & AIMS: Gastric cancer is the fifth most common cancer worldwide. Men are disproportionately affected by gastric cancer, which ranks as the fourth most common cancer in men compared to eighth in women. Chronic inflammation driven by Helicobacter pylori infection remains the leading gastric cancer risk factor. Evidence suggests that sex hormones shape sex differences in infection outcomes and cancer susceptibility. This study investigates how androgens influence the gastric inflammatory response to Helicobacter infection and contribute to sex disparities in pre-dysplastic disease progression.
    METHODS: Male and female mice were colonized with Helicobacter felis. Androgen levels were manipulated by bilateral castration in males and dihydrotestosterone (DHT) treatment in females. Single-cell RNA sequencing was used to identify androgen-responsive leukocyte populations and to establish cell communication networks between leukocyte clusters. The functional roles of these cells were further defined using ILC2- and T cell-deficient mouse models.
    RESULTS: Infected female mice developed significantly more severe gastric inflammation, atrophy, and metaplasia infection compared to males. Androgen depletion by castration increased gastric inflammation and accelerated preneoplastic lesion development, while these pathological features were reduced by DHT treatment. Androgen-responsive type 2 innate lymphoid cells (ILC2s) were key initiators of gastric inflammation, and ILC2 depletion abolished the sex differences in H. felis pathogenesis.
    CONCLUSIONS: This study reveals that androgens protect from Helicobacter-induced gastric inflammation by modulating ILC2 activation. These findings indicate that ILC2s serve as master regulators of Helicobacter-driven gastric inflammation and highlight their role in directing sex differences in the progression of pre-dysplastic disease.
    Keywords:  Gastric Cancer; Helicobacter pylori; Pyloric Metaplasia; Sex-Differences; Testosterone
    DOI:  https://doi.org/10.1016/j.jcmgh.2025.101690
  4. Front Endocrinol (Lausanne). 2025 ;16 1677085
    The hypothalamic effects of PACAP on the hypothalamic-pituitary-gonadal axis in male mice.
    Péter Faludi, Klaudia Barabás, Ferenc Lengyel, Ildikó Udvarácz, Dániel Pham, Olivér Kisjós, Zsuzsanna Nagy, Dóra Reglődi, Gergely Kovács.
      Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal peptide (VIP) neuropeptide family and plays a role in the regulation of several releasing hormones and tropic hormones. The hypothalamic-pituitary-gonadal (HPG) axis governs the synthesis and the release of sex hormones and the gametogenesis in all mammals. While the effects of PACAP on fertility is well-documented in females, much less data are available in males. The aim of our study was to examine potential structural and expressional changes in the hypothalamus that might underlie the fertility deficits observed in male PACAP knockout (KO) mice. To this end, we performed immunofluorescent, immunohistochemical and RNAscope in situ hybridization stainings to detect the protein and/or mRNA expression of gonadotropin-releasing hormone (GnRH), kisspeptin, estrogen receptor alpha (ERα) and androgen receptor (AR) in the hypothalamus. Our results revealed that the number and immunoreactivity of GnRH neurons were lower in the medial preoptic area (MPOA) in PACAP KO mice. In contrast, the number of kisspeptin neurons was higher in the rostral periventricular region of the third ventricle (RP3V) and the mid arcuate nucleus (ARC). Furthermore, higher number of Esr1-positive cells was found in the kisspeptin-rich RP3V and the ARC. Notably, less AR-positive cells, and more ERα-positive cells were detected in the MPOA demonstrating a possible misbalance between estrogenic and androgenic signaling. Our results suggest that neuroendocrine changes induced by PACAP deficiency in the hypothalamus might contribute to the development of reproductive dysfunction in PACAP-deficient males by disrupting normal HPG axis function.
    Keywords:  GnRH; PACAP; androgen receptor; estrogen receptor alpha; kisspeptin
    DOI:  https://doi.org/10.3389/fendo.2025.1677085
  5. J Gen Virol. 2025 Dec;106(12):
    Robust antibody and T cell responses tracked longitudinally in patients with long COVID.
    Marina Metaxaki, Ranjana Ram, Marianne Perera, Mark Wills, Benjamin A Krishna, Nyarie Sithole.
      After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a minority of patients experience persistent or emerging symptoms, termed 'long coronavirus disease (COVID)' or post-acute sequelae of COVID-19. The molecular causes of long COVID remain unclear, but disrupted immune functions, such as inflammation and immune deficit, have been posited as factors. In this retrospective cohort study, we measured markers of immune function in a group of patients with long COVID up to 40 months post infection. As proxies for immune function, we measured serum antibody levels, antibody neutralizing capability and production of IFN gamma (IFN-γ) and IL-2 against SARS-CoV-2 and other viral peptides. As expected, serum antibody levels increased over time with vaccinations and reinfections with later variants of SARS-CoV-2. Patients also showed corresponding increasing SARS-CoV-2-specific IL-2 responses and stable IFN-γ responses. We observed no significant differences in immune responses among patients with ongoing long COVID, those who had recovered from it or individuals who recovered from acute COVID-19. Overall, we found no indication of a reduction in these aspects of immune function after SARS-CoV-2 infection. This study provides a valuable foundation for further research aimed at understanding the causes of long COVID.
    Keywords:  T cell; antibody; long COVID; longitudinal
    DOI:  https://doi.org/10.1099/jgv.0.002172
  6. Biol Sex Differ. 2025 Dec 02.
    Sex-dimorphic reprogramming of fetal mouse brain development by maternal estradiol excess.
    Huihui Wang, Zhe Wei, Yu Zhang, Xiaojun Chen, Li Jin, Chengliang Zhou.
       BACKGROUND: Gestational environmental perturbations can induce sex-specific developmental programming, increasing offspring susceptibility to chronic diseases. While prenatal high estradiol (HE) exposure has been associated with male-biased neurodevelopmental disorders, the underlying mechanisms remain poorly understood.
    METHODS: Using spatial transcriptomics in a murine HE exposure model, we systematically characterized sex-divergent molecular and cellular responses in fetal brains. Through cell type identification, spatial mapping, ligand-receptor interaction analysis, and transcription factor activity assessment, we examined gene expression profile, intra-regional signaling pathway, and regulon activity variations. Additionally, we performed immunofluorescence to characterize neural progenitor cell dynamics.
    RESULTS: Our analysis revealed that maternal HE exposure differentially altered gene expression patterns between male and female fetal brain regions, with more pronounced effects on male-biased genes. Notably, HE-induced downregulation of male-biased genes was proportional to their baseline male-bias degree. We uncovered region-specific cellular responses to HE exposure and demonstrated sex-opposed alterations in intra-regional signaling pathway. Furthermore, we identified cell type- and brain region-restricted sex differences in regulon activity variations. Histological validation confirmed that maternal HE exposure specifically disrupts the proliferation-differentiation balance of neural progenitor cells in the male cerebral cortex.
    CONCLUSIONS: These findings provide mechanistic insights into sex-dimorphic developmental reprogramming of fetal brain by maternal estradiol excess. They establish a framework for developing targeted interventions against gestational endocrine disruption-induced neurodevelopmental disorders.
    Keywords:  Brain development; Development programming; Maternal estradiol; Sex difference; Single-cell RNA sequencing; Spatial transcriptomics
    DOI:  https://doi.org/10.1186/s13293-025-00792-7
  7. J Clin Invest. 2025 Dec 01. pii: e193212. [Epub ahead of print]135(23):
    Transcriptional coregulator ZMIZ1 modulates estrogen responses that are essential for healthy endometrial function.
    Sylvia C Hewitt, Frank Orellana, Ryan M Marquardt, MyeongJin Yi, Cynthia J Willson, Mark Y Chiang, Yong Song, Goutham Venkata Naga Davuluri, Christopher Day, Ramakrishna Kommagani, Joseph Rodriguez, Asgerally T Fazleabas, John P Lydon, Francesco J DeMayo.
      Estrogen is a critical regulator of endometrial health. Aberrant estrogen stimulation can result in infertility, endometrial cancer, and endometriosis. Here, we identified Zinc Finger MIZ-Type Containing 1 (Zmiz1) as a coregulator of uterine estrogen signaling. ZMIZ1 is colocalized with an estrogen receptor α-binding (ESR1-binding) super enhancer. ZMIZ1 mutations are found in endometrial cancer and its RNA levels trend toward reduction in endometrium of patients with endometriosis. ZMIZ1 is dynamically expressed in human endometrial tissues during the menstrual cycle. Disrupting ZMIZ1 in cultured human endometrial stromal cells resulted in impaired cell proliferation and decidual differentiation. Ablation of Zmiz1 using the PgrCre mouse (Zmiz1d/d) resulted in infertility and accelerated age-dependent uterine fibrosis. Zmiz1d/d mice showed reduced ovulation and progesterone levels while maintaining normal serum prolactin during pregnancy. Uteri of Zmiz1d/d mice were unable to undergo a hormonally induced decidual response, had decreased expression of stromal progesterone receptor (PGR) and decreased stromal and epithelial cell proliferation. Analysis of the transcriptome of Zmiz1d/d mouse uteri showed decreased E2F, CCNA2, and FOXM1 signaling. Challenging ovariectomized Zmiz1d/d mice with estrogen resulted in a decreased amplitude of some estrogen-regulated gene responses. Our findings demonstrate the importance of ZMIZ1 as an ESR1 coregulator in uterine biology and pathology.
    Keywords:  Endocrinology; Reproductive biochemistry; Reproductive biology; Sex hormones; Transcription
    DOI:  https://doi.org/10.1172/JCI193212
  8. NPJ Precis Oncol. 2025 Dec 01.
    Androgen receptor splice variant expression and prostate cancer recurrence after salvage therapy.
    David J Konieczkowski, Keisuke Otani, Zoe Guan, Michael R Drumm, Yukako Otani, Priscilla Oluwakemi Badusi, Ella H Chung, Shulin Wu, Elai Davicioni, Philip J Saylor, Chin-Lee Wu, Jason A Efstathiou, David T Miyamoto.
      Prostate cancer is driven by androgen receptor (AR) signaling, and radiotherapy (RT) with or without androgen deprivation therapy (ADT) offers a second opportunity at cure for men with local or biochemical recurrence after prostatectomy. In the metastatic setting, AR RNA splice variants (ARVs), including ligand-independent AR-V7, modulate ADT response and tumor radiosensitivity. Here, we hypothesized that ARVs in primary prostate cancer may likewise modulate response to subsequent salvage RT+ADT. We performed ultra-deep RNA-seq of the AR transcript pool from prostatectomy specimens from 43 men who later received salvage RT+ADT. Eighty-six percent of patients had detectable ARVs (median 3, range 0-12). Of the thirty-two unique ARVs detected, only AR-V7 (present in 14% of patients) was associated with outcomes after salvage RT+ADT (HR for second biochemical failure, 6.2, 95% CI 2.3-16.5, p=0.0003). These results suggest for the first time that AR-V7 may modulate outcomes for localized in addition to metastatic prostate cancer.
    DOI:  https://doi.org/10.1038/s41698-025-01201-3
  9. bioRxiv. 2025 Nov 22. pii: 2025.11.21.689715. [Epub ahead of print]
    Sex differences in gene regulation and its impact on cancer incidence.
    Camila M Lopes-Ramos, Rebekka Burkholz, Marouen Ben Guebila, Viola Fanfani, Enakshi Saha, Katherine H Shutta, Kimberly Glass, John Quackenbush, Dawn L DeMeo.
      Sex differences in the incidence rates of many cancer types are well-documented. While differences in lifestyle, environmental exposures, and hormone levels can influence disease risk and incidence, there is limited understanding of how cancer driver genes are differentially regulated between males and females in normal tissues, and how these differences may contribute to the observed sex differences in cancer epidemiology. We studied 8,279 gene regulatory networks across 29 non-cancerous tissues in the GTEx dataset, referred here as normal tissues. Using network centrality measures, we compared the networks between males and females, focusing on interactions between 644 transcription factors and 476 cancer genes (COSMIC Cancer Gene Census). Cancer genes were differentially targeted by transcription factors in males and females across normal tissues. We found an overrepresentation of sex-biased cancer genes on the X chromosome, particularly among genes escaping X chromosome inactivation, with higher regulatory targeting of tumor suppressor genes in females compared to males. Key signaling pathways, including WNT, NOTCH, and p53, showed differential transcriptional targeting by sex. We observed higher targeting of cancer-related pathways in females for tissues that have higher tumor incidence in females (breast, lung, and thyroid) and higher targeting in males for tissues with increased tumor incidence in males (stomach, colon, and liver). Sex-biased transcription factors that were consistently observed across multiple tissues are enriched for sex hormone response elements in their promoters. Our findings showed that normal tissues have sex-biased regulation of genes implicated in tumorigenesis, helping to explain the molecular basis of sex differences observed in cancer incidence rates and in identifying targets for cancer prevention in a sex-aware manner.
    DOI:  https://doi.org/10.1101/2025.11.21.689715
  10. Clin Med Insights Endocrinol Diabetes. 2025 ;18 11795514251394434
    Sex-Specific Associations of Prolactin and Progesterone With Glycemic Control in Adults With Type 1 Diabetes.
    Abigayle B Simon, Dhruti Trivedi, Jeffrey Thomas, Matthew S Nicholson, Ryan A Harris.
       Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency and impaired glucose regulation. While sex hormones are known to influence insulin sensitivity, their specific roles in T1D remain underexplored. Prolactin and progesterone have been associated with glucose metabolism, yet their influence in individuals with T1D, particularly men, has not been well studied. This study investigated the relationship between key sex hormones and glycemic control in men and women with T1D.
    Methods: Seventy-eight adults with T1D (25 men, 53 women) were recruited for a cross-sectional study examining associations between circulating sex hormone concentrations and hemoglobin A1c (HbA1c). Participants underwent anthropometric and body composition assessments and provided fasting blood samples for measurement of estradiol, progesterone, prolactin, total testosterone, free testosterone, and HbA1c. Pearson's correlations were used to evaluate associations between hormone levels and HbA1c.
    Results: In men, higher concentrations of prolactin (r = -.571, P = .003) and progesterone (r = -.434, P = .030) were significantly associated with lower HbA1c. No such associations were observed in women for prolactin, progesterone, estradiol, or testosterone. Similarly, in men, estradiol, total testosterone, and free testosterone were not significantly correlated with HbA1c.
    Conclusions: This study provides novel evidence that prolactin and progesterone may be linked to improved glycemic control in men with T1D. These associations were not observed in women. The findings underscore the importance of sex-specific approaches in endocrine and metabolic research. Further longitudinal and mechanistic studies are needed to confirm these relationships and explore the potential of prolactin and progesterone as therapeutic targets in T1D management.
    Keywords:  HbA1c; diabetes; glycemic status; hormones; progesterone; prolactin
    DOI:  https://doi.org/10.1177/11795514251394434
  11. Hormones (Athens). 2025 Dec 01.
    New insights into sexual dimorphism in cardiometabolic health.
    Chara Kaldirimitzian, Louiza Kampanella, Konstantina-Maria Chouliara, Eirini-Maria Kavvadia, Vasiliki-Regina Tsinopoulou, Konstantinos I Tsamis, Georgios Boutzios, Melpomeni Peppa, Stavroula A Paschou.
      Sexual dimorphism is evident in several key metabolic processes, extending to the pathophysiology, incidence, and progression of cardiometabolic diseases and forming distinct risk profiles between men and women. This review provides insights into the fundamental mechanisms underlying sexual dimorphism in cardiometabolic disease risk and onset. Sex-specific cardiometabolic health outcomes are correlated with genetic, hormonal, and metabolism-associated risk factors, immunological variations, and lifestyle. Compared to men of corresponding age and BMI, premenopausal women are at lower risk of cardiometabolic disorders-an advantage that disappears after menopause-revealing the adverse health alterations stimulated by chronological and ovarian aging. Despite the increased incidence and morbidity of cardiometabolic diseases, current preventive, diagnostic, and treatment approaches remain non-sex- and non-age-specific and hence partially ineffective. We outline the implications of cardiometabolic sexual dimorphism and explore current strategies, highlighting the significance of age-weighted, sex-distinct prevention and treatment strategies for achievement of improved outcomes.
    Keywords:  Adipose tissue; Cardiometabolic risk; Estrogens; Implications; Menopause; Sex hormones; Sexual dimorphism
    DOI:  https://doi.org/10.1007/s42000-025-00740-5
  12. J Exp Clin Cancer Res. 2025 Dec 02.
    STARD4 suppresses tumorigenesis and attenuates enzalutamide resistance via lipid metabolic reprogramming and AR stabilization in prostate cancer.
    Yi Zhang, Xi Wang, Jiuyi Wang, Ke Ma, Lei Jia, Bo Liu, Xianglin Yuan, Qiang Li, Qinzhang Wang, Qinyu Li, Kai Zeng.
       BACKGROUND: Prostate cancer (PCa) is a globally prevalent malignancy in males and is imposing an increasing epidemiological burden. The androgen receptor (AR) signalling axis is fundamentally implicated in PCa tumorigenesis and disease progression. Although androgen deprivation therapy (ADT) elicits transient therapeutic responses in the majority of cases, progression to castration-resistant prostate cancer (CRPC) remains an almost universal clinical trajectory. Dysregulated lipid homeostasis, manifesting as intracellular lipid deposition, has been mechanistically linked to CRPC pathogenesis and therapeutic failure under enzalutamide regimens. However, effective strategies to mitigate lipid accumulation in PCa remain elusive.
    METHODS: STARD4, a key gene involved in lipid metabolism, was identified as functionally significant in PCa through integrated bioinformatics analysis of public databases. RT‒qPCR, western blot analysis, and IHC staining were performed to evaluate STARD4 expression, while Kaplan-Meier survival analysis, Gleason score, and tumor stage were performed to assess its clinical significance in PCa. The biological functions of STARD4 and its contribution to enzalutamide resistance were elucidated through in vitro and in vivo experiments. The effect of STARD4 on abnormal lipid accumulation in PCa cells was evaluated by Oil Red O (ORO) staining, while its impact on endoplasmic reticulum (ER) stress was assessed through ER-tracking imaging and transmission electron microscopy (TEM). Mechanistic exploration involves a combination of techniques, including RNA-seq analysis, Gene ontology analysis, coimmunoprecipitation (Co-IP), and GST pull-down assay, to analyse the interactions and potential mechanisms involving STARD4, AR, and E3 ubiquitin ligase UBE4B.
    RESULTS: In this study, we observed that STARD4 expression was markedly reduced in PCa tissues and was correlated with an adverse prognosis. STARD4 overexpression inhibited PCa cell proliferation, migration, and lipid accumulation while promoting apoptosis through ER stress. Mechanistically, STARD4 enhanced the interaction between UBE4B and AR, facilitating AR ubiquitination and degradation and thus suppressing AR signalling. Additionally, the upregulation of STARD4 expression enhanced sensitivity to enzalutamide in resistant cells by diminishing lipid accumulation and inhibiting the AR signalling pathway. In summary, STARD4 functions as a tumour suppressor in PCa by regulating cholesterol metabolism and modulating AR signalling.
    CONCLUSIONS: Our findings identify STARD4 as a promising therapeutic target for reversing enzalutamide resistance in PCa while also providing novel insights for future research on lipid metabolism within the tumour microenvironment.
    Keywords:  Androgen receptor; Enzalutamide resistance; Lipid metabolism; Prostate cancer; STARD4
    DOI:  https://doi.org/10.1186/s13046-025-03600-7
  13. Cell Commun Signal. 2025 Dec 02. 23(1): 516
    The interplay of estrogen, gut microbiome, and bone immunity in osteoporosis.
    Maohua Chen, Jiaxu Wang, Yuanhang Yang, Yingge He, Liqi Li.
      Osteoporosis is a global health concern arising from estrogen deficiency, intestinal dysbiosis, and dysregulation of the bone immune system. The absence of estrogen after menopause created environmental changes within the gut, where the microbial growth of the body was disturbed by the endocrine hormone, and inflammation increases due to the gut-bone axis, which leads to heightened bone loss. The gut microbiota, composed of bacteria and their metabolites such as short-chain fatty acids, play a crucial role in bone immune regulation by modulating immune cell function, influencing bone cell activity, and mediating epigenetic modifications. Malfunction of this system, characterized by the activation of immune cells and the imbalance of cytokines, also leads to the development of osteoporosis. Treatment strategies involved the regulation of the dysbiosis of the gut microbiota, reposition estrogen to the body, and immune modulation. The future direction should be the clarification of these interactions between estrogen and intestinal microflora, identification of new therapeutic targets, and personalization of osteoporosis management.
    Keywords:  Estrogen; Gut microbiota; Osteoimmunity; Osteoporosis; Therapeutic strategies
    DOI:  https://doi.org/10.1186/s12964-025-02538-9
  14. J Lipid Res. 2025 Nov 27. pii: S0022-2275(25)00217-2. [Epub ahead of print] 100954
    Serum cholic acid and cecal Faecalibaculum increase in a male-specific manner in a murine hepatocellular carcinoma model.
    Angela E Dean, Douglas V Guzior, Robert A Quinn, Christoper A Gaulke, Sayeepriyadarshini Anakk.
      Hepatocellular carcinoma (HCC) has a higher incidence in males and is a leading cause of cancer-related deaths, which lacks effective therapies and surveillance markers. Using a murine model of bile acid excess (farnesoid X receptor and small heterodimer partner double knockout, DKO), which phenocopies many aspects of HCC, including sex differences, we investigated the links between sex, bile acid metabolism, and microbial composition. Unexpectedly, the increase in the ratios of carcinogenic deoxycholic acid (DCA) was similar between DKO males with HCC and cancer-resistant DKO females. However, both taurine-conjugated and free-cholic acid (CA), sharply increased in the serum of DKO males with free-CA comprising 65% of the bile acid pool, whereas DKO female serum was mostly comprised of conjugated bile acids. Unlike such sex differences in DKO serum composition, conjugated bile acids were predominant in the hepatic BA pool irrespective of the sex or genotype, as expected. Fecal and cecal microbiota - many of which harbor bile acid transformation/ deconjugation capacity- were altered in DKO mice in a sex-specific manner. Untargeted fecal metabolite analysis showed differences in bile acids, phospholipids, and oxidized fatty acids between the genotypes, with DKO females excreting more sulphated and oxidized CA than tumor-bearing DKO males. Further analysis revealed a direct correlation between unconjugated CA levels with the abundance of the microbial genus Faecalibaculum in the DKO HCC model. These findings suggest distinct sex-specific changes in cecal and fecal microbiota, and BA composition may be leveraged in combination as a potential tool for HCC surveillance.
    Keywords:  Bifidobacterium; CA; DCA; Faecalibaculum; Hepatocellular Carcinoma
    DOI:  https://doi.org/10.1016/j.jlr.2025.100954
  15. bioRxiv. 2025 Nov 21. pii: 2025.11.20.689545. [Epub ahead of print]
    Sexually dimorphic role of estrogen receptor α in preserving right ventricular endothelial integrity.
    Jiajun Li, Vijaya Karoor, Andrea L Frump, Hanqiu Zhao, Shunning Liang, Chen-Shan Chen Woodcock, Irina Petrache, Zhiyu Dai, Tim Lahm.
      Right ventricular (RV) function and adaptation to afterload increase determine survival in pulmonary hypertension (PH). RV adaptation in PH is sexually dimorphic and more preserved in females, mediated by protective estrogen receptor α (ERα) signaling in cardiomyocytes. However, the effects of ERα on RV endothelial cells (RVECs), a critical mediator of RV homeostasis and adaptation, are unknown. We hypothesized that ERα exerts sexually dimorphic pro-angiogenic effects on RVECs in vitro and promotes RV vascularization in vivo. Compared to cells isolated from wild-type animals, RVECs from male and female rats with an ERα loss-of-function mutation (ERα Mut ) showed reduced ability to form pseudo-vascular networks and migrate. RVECs from female ERα Mut rats demonstrated increased apoptosis. In a PH model induced by monocrotaline (MCT), female ERα Mut rats exhibited increased RV hypertrophy and reduced RV capillary density before (10 days) and at the time of established PH (28 days). Capillary rarefaction was associated with increased RVEC apoptosis, and, as identified by single-nucleus RNA-sequencing, by a net loss of the endocardial RVEC sub-population. Differentially expressed gene analysis and pathway analysis identified that capillary and endocardial RVECs from female MCT-PH ERα Mut rats demonstrated decreased expression of migration pathways and increased expression of apoptosis pathways. These findings reveal a sex-specific endothelial-intrinsic role of ERα that is essential for angiogenesis in the RV under both homeostatic and pathological conditions. This effect appears to stem from the enhanced survival and migration capacity of capillary and endocardial RVEC. Collectively, our results identify ERα as a potential target for developing sex-specific RV-directed therapies in PH.
    Translational perspective: Effects of ERα on vascular function in RV failure induced by PH are poorly understood. We unveiled a novel sexually dimorphic role of ERα in regulating RV vascularization and RVEC function. Single nucleus RNA-Sequencing in female wild-type and ERα loss-of-function rats with PH identified 5 unique RVEC sub-populations under transcriptional control of ERα. Our findings provide insights into previously undescribed pro-angiogenic, pro-migratory and anti-apoptotic roles of ERα in female RVs and RVECs. Promoting RVEC migration or inhibiting RVEC apoptosis to enhance RV angiogenesis may be viable pathways to maintain RV function in PH patients of either sex. These findings offer novel opportunities and potential therapeutic avenues for preventing or treating RV failure.
    DOI:  https://doi.org/10.1101/2025.11.20.689545
  16. Microbiome. 2025 Dec 05. 13(1): 251
    Microbiota insights in endometriosis.
    Guillaume Parpex, Carole Nicco, Benoît Chassaing, Pietro Santulli, Sandrine Chouzenoux, Mathilde Bourdon, Chloé Maignien, Ludivine Doridot, Frédéric Batteux, Charles Chapron, Louis Marcellin.
      Endometriosis affects approximately 10% of women of reproductive age and is characterized by the presence of endometrial-like tissue outside the uterine cavity, leading to chronic pelvic pain, infertility, and a significant reduction in quality of life. Beyond its local manifestations, endometriosis is increasingly recognized as a systemic, immune-mediated condition with multifactorial origins. In this narrative review, we provide an updated and comprehensive overview of the disease, including its pathophysiology, clinical features, and evolving conceptual frameworks. Considering the frequent digestive symptoms observed in affected patients, we summarize key findings from both animal and human studies that investigate alterations in the gut microbiota. We also review the profound immune dysregulation associated with endometriosis and explore its potential bidirectional relationship with the microbiota. Furthermore, we examine recent insights into the endometrial microbiota-an emerging field of interest given its early involvement in the disease process and its strong interconnection with the vaginal microbiome. Lastly, we highlight studies exploring the gynecological microbiota and present an updated discussion of novel therapeutic strategies, including microbiota-targeted approaches that may shape future management of this complex disease. Video Abstract.
    Keywords:  Endometriosis; Gut microbiota; Gynecological microbiota; Host-microbe interaction; Metabolites
    DOI:  https://doi.org/10.1186/s40168-025-02243-2
  17. J Transl Med. 2025 Nov 29.
    Lactylation at the crossroads of immune metabolism and epigenetic regulation: revealing its role in rheumatic immune diseases.
    Ziheng Zhu, Chuanbing Huang, Junjie Chen, Lei Wan, Chuanwei Zhang, Jianing Wang.
       BACKGROUND: Lactate was traditionally regarded as merely the end product of glycolysis; however, recent discoveries of lactylation have revealed that lactate can also directly serve as a substrate for epigenetic modification, filling a critical gap in the understanding of "metabolite-epigenetic regulation." In rheumatic immune diseases such as rheumatoid arthritis and systemic lupus erythematosus, the affected tissues, including the joint synovium and internal organs, are typically hypoxic. These regions demonstrate pronounced inflammatory infiltration and metabolic reprogramming, leading to the accumulation of lactate within the local microenvironment. In this context, lactylation directly links the metabolic state (lactate levels) of the microenvironment with epigenetic regulation of gene expression. This offers valuable insights into how metabolic cues specifically modulate the functions of immune cells, including polarization, activation, and cytokine secretion, as well as the behavior of tissue-resident cells, such as synovial fibroblasts. Conventional immunosuppressants demonstrate limited efficacy in correcting such metabolic abnormalities; thus, exploring novel mechanisms and therapeutic targets at the intersection of metabolism and epigenetics is urgently needed. Investigating the mechanistic role of lactylation, therefore, represents a crucial step toward developing innovative therapies for rheumatic autoimmune disorders.
    METHODS: This review systematically summarizes the pivotal functions of lactylation within the immune-metabolic and epigenetic regulatory networks, examining its influence on metabolic pathways, chromatin modification, and disease progression. Furthermore, it discusses the modulatory roles of lactylation in immune cell activity, signaling pathway activation, and the generation of disease-specific modification patterns.
    RESULTS: In summary, current evidence indicates that lactylation serves as a molecular bridge connecting "immunometabolism-epigenetic dysregulation-chronic inflammation." Its tissue specificity and diverse modification substrates contribute to a complex regulatory network. Therefore, targeting the lactylation regulatory axis may enable the conversion of pathological metabolic features into therapeutic opportunities.
    CONCLUSION: Future research should emphasize single-cell lactylome profiling and the development of tissue-specific delivery systems to elucidate better and control the dual physiological and pathological functions of lactylation.
    Keywords:  Epigenetic regulation; Immune diseases; Immune metabolism; Lactylation; Metabolic reprogramming; Rheumatic diseases
    DOI:  https://doi.org/10.1186/s12967-025-07498-9
  18. Front Cell Infect Microbiol. 2025 ;15 1680840
    Effect of probiotic-derived metabolites on hormonal and metabolic profiles in women with polycystic ovary syndrome: a systematic review and meta-analysis.
    Maneesh Kumar Maddirevula, Vinod Kumar Nelson, Mohamed Soliman, Bader Khalid Alanazi, Ahmed M S Hegazy, Habeeb Ali Baig, Amro M Soliman, Mansour Alanazi.
       Background: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder linked to insulin resistance and hyperandrogenism. Gut microbiota-derived metabolites, including short-chain fatty acids (SCFAs), indoles, and bile acids, influence endocrine and metabolic pathways. Yet, no systematic review has specifically examined metabolite-targeted interventions in PCOS.
    Objective: To assess the effects of probiotic-derived metabolite interventions on hormonal and metabolic outcomes in women with PCOS.
    Methods: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD42025543210), we searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and two Chinese databases to May 2025 without language restrictions. Eligible studies were randomized or quasi-randomized controlled trials ≥8 weeks. Two reviewers independently screened, extracted data, and assessed risk of bias (RoB 2). Pooled analyses used random-effects models, and evidence certainty was appraised with GRADE.
    Results: Seventeen trials (n = 1, 214 women) were included, testing synbiotics (6), probiotics (7), sodium butyrate (2), Akkermansia muciniphila (1), and an SCFA blend (1). Interventions significantly reduced total testosterone (MD -0.19 ng/mL, 95% CI -0.30 to -0.08), LH/FSH ratio (SMD -0.46; 95% CI -0.66 to -0.26), fasting insulin (MD -2.4 µIU/mL; 95% CI -3.9 to -0.9), and HOMA-IR (MD -0.49; 95% CI -0.78 to -0.19). HDL-C increased modestly (MD + 3.2 mg/dL; 95% CI + 0.7 to +5.6). Evidence certainty was moderate for insulin-related outcomes and low for sex-hormone outcomes.
    Conclusion: STargeting gut-derived metabolites, particularly with sodium butyrate and multi-strain synbiotics, improves hormonal and metabolic markers in PCOS. Larger multicenter RCTs with metabolomic confirmation are warranted to establish clinical translation.
    Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42025543210.
    Keywords:  PCOS; insulin resistance; postbiotics; probiotics; short-chain fatty acids; testosterone
    DOI:  https://doi.org/10.3389/fcimb.2025.1680840
  19. Transgend Health. 2025 Oct;10(5): 428-437
    The Utility of Serum Free Testosterone Concentrations in Monitoring Gender-Affirming Testosterone Therapy in Transmasculine Youth with Obesity.
    Jeremi M Carswell, Ellis Barrera, Enju Liu, Stephanie A Roberts.
       Purpose: This study aimed to explore the use of serum free testosterone concentrations in transmasculine patients as a more reliable indicator of gender-affirming testosterone therapy than total testosterone concentration. Total testosterone values, recommended by current guidelines, may be impacted by obesity. In addition, this study aimed to characterize the impact of testosterone concentrations on hematocrit and the risk of polycythemia.
    Methods: A retrospective study was conducted of transmasculine patients seen at Boston Children's Hospital Gender Multispecialty Service from 2007 to 2020. Sixty-eight birth-assigned female adolescents who were receiving gender-affirming testosterone therapy and had total and free testosterone concentrations were included. The aims were to determine the fidelity of total and free testosterone concentrations with body mass index (BMI) and to characterize the association of testosterone concentrations with erythrocytosis.
    Results: Of 68 subjects, 23% were overweight and 40% had obesity. Compared with the group with a healthy BMI, patients with obesity had significantly lower total testosterone concentrations. Free testosterone concentrations did not vary based on BMI category. BMI z-score was inversely correlated with total testosterone, sex hormone-binding globulin, and albumin concentrations but not with free testosterone concentrations. Four percent of subjects developed erythrocytosis (e.g., hematocrit >50%). Neither BMI nor testosterone concentrations were correlated with hematocrit.
    Conclusions: Free testosterone concentrations are an adjunctive tool in the monitoring of gender-affirming testosterone therapy. In addition, the development of erythrocytosis is independent of serum testosterone concentration and warrants further study to understand factors that may predispose patients to developing secondary polycythemia.
    Keywords:  free testosterone; gender diverse; gender-affirming hormones; testosterone; transgender
    DOI:  https://doi.org/10.1089/trgh.2022.0215
  20. Mol Neurobiol. 2025 Dec 01. 63(1): 223
    Sex-Specific Molecular Architecture of Microglia-Mediated Neuronal Pruning Across the Human Lifespan.
    Cristina Sanfilippo, Paola Castrogiovanni, Rosa Imbesi, Michele Vecchio, Michelino Di Rosa.
      Sex-specific differences in neurodegenerative disease susceptibility suggest distinct molecular mechanisms underlying brain aging between males and females. In this study, we investigated transcriptomic profiles of complement system components, microglial markers, and astrocyte/neuronal proteins across the lifespan to elucidate sex-dependent synaptic pruning mechanisms. Comprehensive transcriptomic analysis was performed on brain tissue samples spanning multiple age groups and regions, examining expression patterns of complement genes (C1QA, C1QB, C1QC, C1R, C1S, C3, ITGAM, ITGB2), microglial markers (TMEM119, P2RY12, CSF1R, NLRP3, TREM2, AIF1), and astrocytic, neuronal, and tissue markers (MAP2, SYP, SNAP25, MAPT, GFAP, CHI3L1). Complement system components demonstrated pronounced sex bias. Males exhibited distinct U-shaped age-related patterns, with middle-late childhood (MLC) consistently showing the highest expression for most genes, decreasing in middle age, followed by partial reactivation in nonagenarians, and then a further reduction in centenarians. An oscillatory trajectory across the lifespan was observed in females, with a peak in centenarians. Regional analysis revealed diencephalic predominance and occipital suppression patterns. Microglial activation markers exhibited complex sex-dependent patterns, with males showing higher expression during childhood/adolescence and females demonstrating an elevation in advanced age. These genes displayed limbic and diencephalic enrichment with cerebellar reduction. Neuronal/astrocytic markers showed opposing trajectories: neuronal markers (MAP2, SNAP25, SYP, MAPT) generally declined with age, while astrocytic markers (GFAP, CHI3L1) increased. Males demonstrated compartmentalized gene clustering, while females showed integrated neuro-microglial networks. Functional enrichment analysis confirmed these networks coordinate complement-mediated synapse pruning, representing systematic age-related synaptic remodeling mechanisms that differ fundamentally between sexes and may influence neurodegenerative susceptibility patterns. These findings demonstrate that female brains maintain heightened complement-mediated synaptic pruning throughout aging, representing a double-edged mechanism that may confer adaptive plasticity while increasing vulnerability to neurodegeneration. Male brains exhibit more stable neuronal environments with reduced glial activation, potentially underlying sex-specific trajectories in brain aging and neurodegenerative disease susceptibility.
    Keywords:  Brain aging; Complement system; Microglial activation; Neuronal pruning; Sex differences
    DOI:  https://doi.org/10.1007/s12035-025-05547-4
  21. Poult Sci. 2025 Nov 19. pii: S0032-5791(25)01380-X. [Epub ahead of print]105(1): 106140
    Dual Salmonella vaccination attenuates microbiota dysbiosis and enhances microbiota functionality in poultry challenged with S. Typhimurium.
    L Montoro-Dasi, L Lorenzo-Rebenaque, A Marco-Fuertes, L Sisquella, M Gomez, P Soler, F Marco-Jiménez, C Marin.
      Salmonella is a leading cause of gastrointestinal illness and foodborne outbreaks worldwide, with poultry products such as eggs as the primary source of infection. In this context, live attenuated vaccines play a critical role in reducing the risk of infection in poultry flocks. However, their impact on the gut microbiota remains poorly understood. Thus, the aim of this study was to evaluate the effects of a live attenuated combined vaccine against Salmonella Enteritidis and Salmonella Typhimurium on the gut microbiota of chicks challenged with S. Typhimurium, including the study of microbial balance and functionality. The trial involved 40 specific pathogen-free chicks, divided into vaccinated and control groups, all challenged with S. Typhimurium at 14 days of age. Afterwards, caecal content of 10 animals per group was collected at 7 and 14 days post infection. Then, the composition, diversity and functionality of the microbiota were analyzed using 16S rRNA sequencing and bioinformatic analysis. The results of the taxonomic analysis revealed 1,261 bacterial taxa, with Firmicutes and Proteobacteria as the dominant phyla. In addition, vaccination resulted in significant changes in microbiota composition, with marked differences in microbial diversity between groups. PLS-DA and Bayesian analysis identified key species such as Clostridium innocuum in vaccinated chicks and Eubacterium coprostanoligenes in the control group. Results also showed that vaccination promoted the growth of beneficial genera such as Lactobacillus and Blautia, which was associated with reduced Salmonella colonization and shedding. Alpha diversity analysis revealed significantly higher microbial richness and evenness in the control group. Finally, functional annotation revealed shared microbial functions between the groups, with potentially pathogenic bacteria, including Salmonella, present in both. These results suggest that vaccination improves microbiota stability and supports the protective role of beneficial bacteria against Salmonella, highlighting the importance of vaccination in improving poultry health and pathogen control throughout the food chain.
    Keywords:  Functionality; Microbiome; Salmonella typhimurium; Vaccination; Zoonosis
    DOI:  https://doi.org/10.1016/j.psj.2025.106140
  22. Front Physiol. 2025 ;16 1676624
    Evaluation of donor's hormonal profile according to sex and age.
    for TransplantLines investigators
      Successful organ transplantation depends on several factors, including donor and recipient sex and age. Experimental data show that donor inflammatory status can be influenced by sex hormones, and, after brain death, there are significant differences in organ quality. Sex hormones also influence the immune system during different life stages, for example, during menopause there is a significant reduction in estrogen levels. Thus, the primary aim of this study is to evaluate the steroid profile of human donors after brain death. We performed a retrospective observational case-control study and selected samples from living (LD) and brain-dead (BD) donors from the TransplantLines Biobank and Cohort Study. Donors were stratified by age as Young (Y) from 20-40 years and Old (O), older than 55 years. Serum steroidal hormones from one hundred donors were analysed through LC-MS (Liquid Chromatography-Mass Spectrometry). In BD-females, cortisol and estradiol decreased significantly (p = 0.0001) in both age groups when compared to LD. However, an increase in progesterone was seen after BD for older donors (p = 0.0001). In BD-males, cortisol decreased significantly in both age (p = 0.0001) groups when compared to LD. For testosterone, the results were similar as BD decreased the steroid levels (p = 0.0001) compared to LD in both age groups. In conclusion, our results indicate that steroid hormone levels decrease after brain death.
    Keywords:  age; brain death; cortisol; estradiol; hormones; progesterone; sex; testosterone
    DOI:  https://doi.org/10.3389/fphys.2025.1676624
  23. Biol Sex Differ. 2025 Dec 03.
    Perinatal citalopram exposure alters the gut composition and microbial metabolic profiles of Sprague-Dawley rat dams and female offspring but not male offspring.
    Dawson R Kropp, Matthew E Glover, Rupabali Samanta, Keaton A Unroe, Sarah M Clinton, Georgia E Hodes.
       BACKGROUND: Selective serotonin reuptake inhibitors are widely prescribed during pregnancy. Their main route of administration is through the gut. However, their impact on the maternal and offspring gut microbiome and microbial metabolic pathways remains poorly understood. This study used metagenomic shotgun sequencing to examine the effects of perinatal citalopram exposure in rat dams and their offspring on gut composition and downstream metabolic pathways.
    METHODS: We treated pregnant and nursing rat dams with either citalopram or vehicle (water). Their feces were collected, DNA from these samples was extracted and then sequenced using shotgun metagenomic sequencing. The BioBakery suite of microbiome analysis tools was utilized in tandem with RStudio to analyze the gut composition and microbial metabolic pathways of the rat dams and their offspring.
    RESULTS: Pregnant and nursing dams treated with citalopram exhibited marked shifts in microbial community structure, including phylum-level alterations in Proteobacteria and Defferibacteria. Citalopram treated dams displayed significantly altered beta diversity. Species level alterations due to treatment were composed of five significantly altered microbes, two of which belong to the Proteobacteria phylum. These changes were highly diverse and were not congruent with microbe-level alterations observed in offspring. Alpha diversity of microbial metabolic pathways was compared using the Gini-Simpson index, which was significantly increased in dams suggesting greater metabolic functional diversity with age. Female offspring perinatally exposed to citalopram showed significant changes in gut beta diversity, with seven significant alterations at the microbe level. These microbial shifts were accompanied by twenty-one significantly altered microbial metabolic pathways. In contrast, male offspring showed no significant differences in microbial composition or beta diversity and only minor metabolic changes.
    CONCLUSIONS: These findings demonstrate that maternal citalopram exposure during pregnancy and lactation has lasting, sex-specific impacts on the offspring's gut microbiome and microbial metabolic pathways. The pronounced alterations in female, but not male offspring, suggest that host sex may be a critical determinant in the developmental response to citalopram exposure. This work underscores the value of metagenomic approaches in uncovering complex host-microbiome interactions and highlights the need to consider offspring sex in evaluating the safety and long-term effects of antidepressant use during pregnancy.
    Keywords:  Gut microbiome; Metagenomics; Next generation sequencing; Rat; SSRI; Shotgun sequencing; Sprague-Dawley; Whole genome sequencing
    DOI:  https://doi.org/10.1186/s13293-025-00794-5
  24. Front Immunol. 2025 ;16 1673072
    Biological sex as a variable in immunity does not affect parabolic flight-induced alterations in immune responses.
    Dominique Moser, Judith-Irina Buchheim, Katharina Biere, Sandra Matzel, Federico D Amico, Alexander Choukér, Tobias Woehrle, Matthias Feuerecker.
      The present era of spaceflight is accompanied by two meaningful breakthroughs. The access to in-orbit missions for civilians and the increasing enrolment of female astronauts require detailed investigations on the impact of gravitational stress on human physiology with focus on sex-specific differences. To assess the responsive capacities of innate and adaptive immunity in this context, functional characterizations were performed in women and men in a parabolic flight study. Blood and saliva were collected 1 month prior and on the day before the flight, as well as directly after flight and on the following day. Leukocyte proportions were quantified, and NETosis as well as phagocytic activity was tested. The impact of gravitational stress on the ability to mount a functional immune response was examined by a 6-h whole-blood incubation assay with subsequent analysis of leukocyte surface activation marker expression and cytokine secretion. Parabolic flight induced a temporary increase in granulocyte proportions, which however did not influence NETosis and phagocytosis. Throughout the flight week, leukocyte activation and cytokine secretion patterns remained unaltered in response to antigen stimulation. No differences were found regarding the direction or intensity of immune response either in women or in men. However, when comparing effects 1 month before flight and the flight week, immune responses were still present but remarkably weaker during flight week, which was independent of cortisol levels. Altogether, this study elicited two important findings. Firstly, no sex-specific increased risk exists for immune dysregulation by acute gravitational stress. Secondly, merely changing the day to day surrounding dampens crucial immune responses, which requires further investigations.
    Keywords:  gravitational stress; innate and adaptive immunity; parabolic flight; sex-specific medicine; whole-blood incubation assay
    DOI:  https://doi.org/10.3389/fimmu.2025.1673072
  25. bioRxiv. 2025 Nov 18. pii: 2025.11.18.689040. [Epub ahead of print]
    Females with Obesity Exhibit Greater Influenza Vaccine-induced Immunity and Protection than Males in a Mouse Model.
    Brian Wolfe, Saurav Pantha, Saranya Vijayakumar, Shristy Budha Magar, Tawfik Aboellail, Santosh Dhakal.
       Introduction: Obesity is increasing globally, and it negatively impacts influenza vaccine efficacy. Although sex differences in influenza vaccine responses are studied in non-obese hosts, studies investigating sex differences in influenza vaccine-induced immunity and protection during obesity are limited.
    Materials and methods: Using the C57BL/6J mouse model of high-fat diet (HFD)-induced obesity or low-fat diet controls, we investigated sex differences in influenza vaccine-induced immunity and protection during obesity. Male and female mice with or without obesity were vaccinated intramuscularly twice at a 3-week interval with an inactivated 2009 H1N1 influenza A virus (IAV) vaccine. At 35 days post-vaccination (dpv), antibody responses in plasma and B- and T-cell responses in spleen and bone marrow were quantified. At 42 dpv, mice were intranasally challenged with a drift variant of the H1N1 IAV, and disease severity was assessed by monitoring the change in body mass up to 21 days post-challenge (dpc). Subsets of mice were euthanized at 3 dpc to determine pulmonary virus replication (TCID 50 assay), histopathology (H&E staining), and cytokine/chemokine responses (multiplex ELISA).
    Results: Female mice, irrespective of diet and obesity status, developed higher antibody responses and were better protected compared to males. Vaccinated males with obesity mounted the poorest antibody responses, experienced a more severe disease, were unable to clear replicating virus from the lungs effectively, and demonstrated heightened pulmonary inflammation. Despite these differences, splenic B- and T-cell frequencies were comparable, suggesting the inefficiency of B cells to produce antibodies in males but not in females with obesity.
    Discussion: Our findings suggest that sex differences is observed in influenza vaccine-induced immunity and protection during obesity, where males are more severely affected. These findings highlight the importance of considering biological sex and obesity status in influenza vaccine design and testing.
    DOI:  https://doi.org/10.1101/2025.11.18.689040
  26. Front Microbiol. 2025 ;16 1651975
    Sex-specific gut microbiome dynamics in Labeo catla: links to reproductive hormones, metabolic dimorphism, and environmental factors.
    Jitendra Kumar Sundaray, Madhusmita Mohapatra, Avinash Rasal, Uday Kumar Udit, Sriprakash Mohanty, Debasrita Mohanty, Ipsita Iswari Das, Lakshman Sahoo, Pramoda Kumar Sahoo.
       Introduction: Gut microbiota play a critical role in aquaculture by enhancing nutrient metabolism, digestion, immune response, and reproductive performance in fish. Labeo catla, one of the most commercially important Indian major carps, demands better reproductive management; however, insights into its gut microbiome composition and functional dynamics, particularly during the crucial pre-spawning phase, remain limited.
    Methods: In this study, we investigated the structural and functional attributes of gut microbial communities in male and female L. catla reared in ICAR-CIFA ponds using high-throughput Illumina MiSeq 16S rRNA gene sequencing and examined their associations with reproductive traits.
    Results and discussion: Histological analysis confirmed active gametogenesis in both sexes, while hormonal assays showed higher estradiol levels in females compared to males. Microbiome profiling revealed Proteobacteria as the dominant phylum, followed by Fusobacteria, Bacteroidetes, and Firmicutes. Cetobacterium and Shewanella were the most prevalent genera, with sex-specific differences in microbial diversity and composition. Functional prediction analysis identified genes associated with reproduction, lipid metabolism, digestion, and immunity. Correlation studies revealed a negative association between Bacteroidetes and 11-KT, while Shewanella and Serratia showed positive correlations with estradiol, indicating a potential role of gut microbes in modulating reproductive readiness. Canonical Correspondence and variance partitioning analyses revealed that gut microbiome variation in male and female L. catla was predominantly influenced by biological factors (63.97%) compared to environmental factors (20.99%). Notably, despite their low abundance, Clostridium perfringens and Pseudomonas stutzeri were identified as keystone taxa significantly shaping microbial network structure and stability.
    Conclusion: This study provides the first comprehensive insight into the sex-specific gut microbiome's dynamics in L. catla during the pre-spawning season and highlight their application in broodstock management and sustainable aquaculture practices.
    Keywords:  biological factors; environmental factors; functional diversity; gut microbiota; high-throughput sequencing
    DOI:  https://doi.org/10.3389/fmicb.2025.1651975
  27. Proc Natl Acad Sci U S A. 2025 Dec 09. 122(49): e2518507122
    TGFBR2 coordinates the endometrial response to estrogen, regulating endometrial hyperplasia and fertility.
    Sydney E Parks, Suni Tang, Anna Catherine Unser, Ananya L Bhonsley, Eunbi M Chung, Peixin Jiang, Audrey Savolainen, Vanessa J Joseph, Dominique I Cope, Ramya P Masand, Renata Prunskaite-Hyyryläinen, Diana Monsivais.
      Proper endometrial function is critical for establishing and maintaining healthy pregnancies, as well as preventing the pathogenesis of conditions such as endometrial hyperplasia and endometrial cancer. The TGFβ signaling pathway regulates key aspects of endometrial biology, although the direct effects of many individual receptors remain unstudied. In this study, we characterize the role of TGFβR2 within the endometrium using a progesterone receptor-cre conditional knock-out mouse model (Tgfbr2flox/flox;Pgrcre/+; "Tgfbr2 cKO"). We found that conditional deletion of TGFβR2 resulted in female infertility, endometrial hyperplasia, altered estrogen and progesterone response, and, only in bred females, reproductive tract tumors. Pregnancy abnormalities in these females began in the prereceptive and implantation stages and compounded throughout gestation, presenting errors in decidualization, immune cell invasion, and early spiral artery formation. Tgfbr2 cKO females had endometrial epithelial hyperplasia at 13 to 14 wk of age, with a significant and region-specific reduction in glandular FOXA2 expression. While this hyperplasia did not advance to malignancy in virgin females, Tgfbr2 cKO females continuously bred for 6 mo all presented with reproductive tract tumors at the time of collection. Mechanistically, we show signaling via TGFβR2 attenuates estrogen signaling while bolstering progesterone signaling in the endometrial epithelium. By integrating ER and SMAD4 genome-wide binding studies with transcriptomic datasets, we demonstrate that both ER and SMAD4 are required for Pgr transcription. In this study, we highlight the importance of TGFβR2 in endometrial function and female fertility and shed light on the potential involvement of TGFβ signaling in estrogen and progesterone response regulation during early pregnancy.
    Keywords:  endometrial hyperplasia; endometrium; estrogen response; organoids; pregnancy
    DOI:  https://doi.org/10.1073/pnas.2518507122
  28. Biol Sex Differ. 2025 Dec 04.
    A visualization tool for individual gene expression profiles among males and females in GTEx tissues.
    Kuo-Feng Tung, Wen-Chang Lin.
      Sexual dimorphism has been implied to certain human physiology and diseases. This topic has recently garnered more attention, highlighting individual variances in precision medicine and individualized clinical trials. It is recognized that individual gene expression variations in males and females could have profound physiological impacts. Tissue specific expression profiles determine protein-coding gene activities and contribute additional physiological variations. Therefore, tissue specific gene expression profiles should be comprehensively analyzed among individual human subjects. In this report, we developed a user-friendly bioinformatic tool to visualize gene expression levels and variances across tissue samples, aiming to facilitate research into potential sexual dimorphism genes. The Gini coefficient metric was used with the most recent GTEx V10 datasets to examine variations in the expression profiles of human protein-coding genes across 43 tissue subtypes. Next, these variations were specifically evaluated using the Gini coefficient index for male and female individuals across all tissue subtypes. Our web-based visualization tool generated tissue specific expression profiles for individual male and female samples. It concurrently illustrates expression levels and variation comparisons between male and female groups across all tissue subtypes. Although most protein-coding genes had similar expression variation patterns between the two sexes, several genes exhibited distinct variations for some tissue subtypes, as indicated by their significant Z-scores in Gini index disparities. Users can explore differentially expressed protein-coding genes across tissue subtypes or search for genes of interest in the Tissue Prominent Sexual Dimorphism Gene database (https://tpsdg.ibms.sinica.edu.tw). This database can be employed to visualize expression levels and variations among individual samples within specific tissues, thereby facilitating future research into divergently expressed protein-coding genes in the human population.
    Keywords:  Bioinformatic visualization interfaces; GTEx project; Gini coefficient index; Protein-coding gene; Sexual dimorphism; Tissue specific expression
    DOI:  https://doi.org/10.1186/s13293-025-00796-3
  29. Res Sq. 2025 Nov 17. pii: rs.3.rs-7960157. [Epub ahead of print]
    Sex differences in antibody responses to influenza A/H3N2 across the life course.
    C Jessica Metcalf, Siyu Chen, Bernardo García-Carreras, James Hay, Huachen Zhu, Chao Jiang, Kin Kwok, Steven Riley, Jonathan Read, Justin Lessler, Derek Cummings.
      Sex differences in both innate and adaptive immunity are increasingly recognized as shaping responses to a range of pathogens. For antigenically variable pathogens that infect people many times over their lifetime, like influenza, sex differences may accumulate or be obscured by the interplay of immunity derived from each infection and future risk. However, sex-specific lifetime trajectories of influenza immunity are poorly characterized. Here, we analyzed hemagglutination inhibition antibody titers to multiple strains of influenza A/H3N2, measured in individuals spanning a wide age range to disentangle strain-specific and cross-reactive antibody responses by sex. To account for potential differences in exposure, we separately analyzed antibody titers to: (1) viruses circulating during an individual's lifetime, and (2) viruses isolated before birth (pre-birth) or after sampling, with responses to the latter interpreted as exclusively cross-reactive, given the absence of possible exposure to these strains. We found that females aged 15 to 40 generally have higher antibody titers than males against pre-birth and post-sampling strains, consistent with greater cross-reactivity. Conversely, older males have stronger responses to strains that they could have encountered during their lives, suggesting that they mount stronger responses upon infection.
    DOI:  https://doi.org/10.21203/rs.3.rs-7960157/v1
  30. World J Surg Oncol. 2025 Dec 01.
    The impact of androgen deprivation therapy and novel hormonal therapy on thyroid hormone levels in prostate cancer patients: a systematic review and meta-analysis.
    Haidi Chu, Yanqing Qu.
       BACKGROUND: Although androgen deprivation therapy (ADT) and novel hormonal therapy (NHT) have improved the prognosis of prostate cancer (PC), the effect of ADT/NHT on thyroid hormone (TH) levels is highly controversial. We performed a systematic review and meta-analysis of peer-reviewed studies to investigate the effects of ADT/NHT on TH levels in PC patients.
    METHOD: Medical literature databases such as PubMed, Web of Science and Metstr were systematically searched for all potentially related clinical studies from their inception to July 10, 2025. The quality of the studies included in the review was evaluated using RevMan version 5.3 for the meta-analysis.
    RESULTS: The systematic review and meta-analysis were based on 413 cases selected from three publications. No significant difference in thyroid stimulating hormone (TSH) levels was observed between the ADT and control groups (MD 0.23 [95% CI -0.01-0.48]; p = 0.06, I2 = 0%), but a significant difference in FT4 levels between the ADT and control groups was observed (MD -0.77 [95% CI -1.50--0.03]; p = 0.04, I2 = 57%).
    CONCLUSIONS: For the first time, we showed no significant difference in the TSH level between the two groups, which might indicate that the TSH level was not affected by ADT in PC patients. Notably, in European countries, patients with long-term ADT were more likely to have lower FT4 levels than non-ADT patients were, but interestingly, all FT4 levels were within their reference intervals.
    Keywords:  Androgen deprivation therapy; Meta-Analysis; Novel hormonal therapy; Prostate cancer; Thyroid hormone levels
    DOI:  https://doi.org/10.1186/s12957-025-04126-0
  31. J Assist Reprod Genet. 2025 Dec 04.
    Effect of improvement in the endometrial microbiome on in vitro fertilization outcomes.
    Masachi Hanaoka, Kanako Hanaoka, Mayu Yamada.
       PURPOSE: The uterine microbiome of in vitro fertilization (IVF) patients was analyzed using next-generation sequencing (NGS) targeting 16S rRNA. Lactobacillus spp. were examined, with a special focus on Lactobacillus iners. The effects of antibiotic therapy on pregnancy outcomes were investigated.
    METHODS: A total of 257 IVF patients underwent endometrial microbiome testing. Patients were initially classified based on the percentage of Lactobacillus spp. into the Lactobacillus-dominant microbiome (LDM) group and the non-LDM group using a cutoff of 90%. Treatment was provided to non-LDM patients. Treated patients who improved on the second test were included in the Post-treatment group, and their pretreatment status was also examined.
    RESULTS: Lactobacillus was dominant in many IVF patients, but some patients showed Gardnerella or other bacteria associated with bacterial vaginosis. The treatment improvement rate for the non-LDM group was 81.4%, with an equivalent or better pregnancy success rate compared with the LDM group. The effect on pregnancy outcomes of Lactobacillus may differ by species, with L. crispatus and L. gasseri tending to act positively, whereas L. iners at ≥ 74.2% acts negatively.
    CONCLUSIONS: This study shows that the recovery of an LDM in non-LDM IVF patients improves the composition of the endometrial microbiome, and pregnancy outcomes approach those of patients initially having an LDM. Furthermore, in LDM cases, L. iners species were also associated with lower pregnancy rates. These findings suggest that both the presence and type of Lactobacillus species are important for IVF success and that targeted microbiome treatment may improve reproductive outcomes.
    Keywords:   Lactobacillus iners ; Lactobacillus-dominant microbiome (LDM); 16S ribosomal RNA; Assisted reproductive techniques; Endometrial microbiome
    DOI:  https://doi.org/10.1007/s10815-025-03759-0
  32. Anim Reprod Sci. 2025 Dec 01. pii: S0378-4320(25)00290-8. [Epub ahead of print]284 108051
    Deslorelin influences canine epididymal gene expression of the androgen receptor and prostaglandin metabolism.
    Henriette Greiner, Eva-Maria Packeiser, Hanna Körber, Sabrina Stempel, Fritjof Freise, Sandra Goericke-Pesch.
      Deslorelin slow-release implants (DSRI) reversibly suppresses testicular function in dogs, although the effects on the epididymis remain poorly investigated. As prostaglandins E2 and D2 contribute to epididymal function, presumably regulated by androgens, corresponding metabolic enzymes and receptors were examined in an explorative study. Epididymides of three untreated dogs (CG) were compared with five epidymides obtained by unilateral hemicastration after five months of DSRI treatment (TG), and with the recovered epididymis of the other side, collected five months after implant removal (RG). Gene expressions (RT-qPCR) of the androgen receptor (AR), the synthases PTGS2, PTGES, L-PGDS, and H-PGDS, the receptors EP2, EP4, and DP, as well as prostaglandin inactivator HPGD were compared between groups (CG/TG/RG) and epididymal segments (head/body/tail). Protein localization was evaluated immunohistochemically for AR, PTGS2, HPGD, PTGES, EP2, and EP4. Gene expression differed between TG and CG for all genes except for AR (all P < 0.05), with increased expression in the head (PTGS2, HPGD, PTGES, EP4, HPGDS, and DP). Surprisingly, the only significant difference between RG and TG or CG was a higher PTGS2 expression in the tail in CG (P < 0.05). Friedman tests revealed segment-specific gene expressions within TG (DP), RG (AR, HPGD, EP2, EP4, and L-PGDS), and CG (AR, EP2, L-PGDS) (all P < 0.05), indicating segment-specific function, although without significance in post-hoc tests. Specific immunostaining was confirmed in all samples. Unexpectedly, the DSRI did not alter AR expression, but reversibly affected genes expression within the prostaglandin metabolism. Due to the low sample size, this conclusion must be considered preliminary.
    Keywords:  Androgen; Deslorelin slow-release implant; Dog; Epididymis; Prostaglandin
    DOI:  https://doi.org/10.1016/j.anireprosci.2025.108051
  33. Front Oral Health. 2025 ;6 1663817
    Prenatal maternal salivary hormones and timing of tooth eruption in early childhood: a prospective birth cohort study.
    Ying Meng, Ruqian Yang, Nora Alomeir, Thomas G O'Connor, Jerod M Rasmussen, Felicitas B Bidlack, Jin Xiao.
       Background: Although the mechanisms underlying tooth eruption are not fully understood, the prenatal maternal milieu, particularly stress exposures, appears to play an important role in dental development. Yet, limited research has investigated the influence of prenatal stress and stress-related hormones on tooth eruption.
    Methods: This study included 142 mother-child dyads from a birth cohort to examine associations between prenatal stress, stress-related hormones, and primary tooth eruption. The number of erupted teeth was assessed by dentists at child visits through 24 months of age. Maternal prenatal depression and anxiety diagnoses were extracted from medical records as a proxy for stress. Stress-related hormone concentrations, including cortisol, estradiol, progesterone, testosterone, triiodothyronine (T3), and thyroxine (T4), were measured from salivary samples collected in late pregnancy. Generalized linear models were used to assess associations between prenatal stress, stress-related hormones, and tooth eruption, adjusting for relevant covariates.
    Results: Eruption timing varied within our cohort: 15.2% of children had at least one erupted tooth by 6 months, and 25% had all 20 primary teeth by 24 months. Correlations in tooth counts across visits ranged from 0.15 to 0.57. Several prenatal maternal hormones, including cortisol, estradiol, progesterone, testosterone, and T3, were significantly and positively associated with the number of erupted teeth at individual visits (p < 0.05). Particularly, higher prenatal cortisol levels were associated with more erupted teeth at 6 months, corresponding to an average difference of ∼4 teeth between the lowest and highest cortisol levels.
    Conclusion: Maternal salivary hormone levels in late pregnancy may contribute to variations in primary tooth eruption during the first two years of life.
    Keywords:  cortisol; prenatal stress; sex steroid hormones; thyroid hormones; tooth eruption
    DOI:  https://doi.org/10.3389/froh.2025.1663817
  34. Nat Commun. 2025 Dec 02. 16(1): 10415
    Large-scale characterisation of the nasal microbiome redefines Staphylococcus aureus colonisation status.
    Dinesh Aggarwal, Katherine L Bellis, Beth Blane, Marcus C de Goffau, Josef Wagner, Duncan Y K Ng, Kathy E Raven, Plamena Naydenova, Stephen Kaptoge, Susan Burton, Rachel Henry, Catherine Perry, Matthew R Walker, Carmel Moore, Carol Churcher, Sophia T Girgis, Catarina Ribeiro de Sousa, Lauma Sarkane, Joe Brennan, Asha Akram, Shannon Duthie, Elisha Johnson, Mercedesz Juhasz, David Anderson, Susan Irvine, Amy McMahon, Liz Lay, Susannah J Salter, Claire Raisen, Xiaoliang Ba, Mark Holmes, Andries J van Tonder, Emanuele Di Angelantonio, Adam S Butterworth, Joan A Geoghegan, John Danesh, Julian Parkhill, Sharon J Peacock, Ewan M Harrison.
      Staphylococcus aureus colonises the nose in humans, with individuals defined as persistent, intermittent or non-carriers. Unlike the gut microbiome, the nasal microbiome has not been studied in large numbers of people. Here, we define the nasal microbiome in ~1100 individuals from the CARRIAGE study (ISRCTN: ISRCTN10474633) and combine with S. aureus culture data. We identify seven community state types (CST), including two CSTs more common in females. Approximately 70% of those who are persistently colonised with S. aureus have a CST dominated by S. aureus, while non-carriers are distributed across the other six CSTs. Intermittent carriers are not a unique state but have microbiomes that resemble non- or persistent carriers. Persistent carriage is positively associated with S. aureus abundance, and negatively associated with three Corynebacterium species, Dolosigranulum pigrum, Staphylococcus epidermidis, and Moraxella catarrhalis; the microbiome can be exploited with machine learning to accurately predict the persistence of S. aureus colonisation. Finally, we find that certain S. aureus lineages are better adapted to colonisation than others. Our data provides a comprehensive view of the nasal microbiome with respect to S. aureus colonisation, describing two key states: a S. aureus dominated CST in which S. aureus shapes the microbiome, and CSTs in which S. aureus is rare or absent.
    DOI:  https://doi.org/10.1038/s41467-025-66564-4
  35. Microb Genom. 2025 Dec;11(12):
    Cervicovaginal microbiome composition and absolute quantity are associated with pelvic inflammatory disease.
    Laurence Don Wai Luu, Ciara Bryant, James Brown, Mark Turner, Thi Huong Pham, Rami Mazraani, Catherine Burke, Brittany Jury, Manisha Shrestha, Kirsty Fleming, Deborah Bateson, Darren Russell, Faith Bassett, Evonne Ong, Jane S Hocking, Sally Sweeney, Wilhelmina May Huston.
      Pelvic inflammatory disease (PID), which involves infection and inflammation of the female reproductive tract, can lead to sequelae including chronic pelvic pain, ectopic pregnancy and tubal factor infertility. A causative pathogen is not identified in many PID cases (idiopathic PID) and does not develop in all women with a sexually transmitted infection or bacterial vaginosis. Therefore, there is a need to better understand the pathogenesis of PID. A case-control study was conducted to explore microbiome, antibiotic resistance and immune gene expression in PID. Microbial profiling using both 16S rRNA gene amplicon and metagenomic approaches revealed that bacterial vaginosis-associated bacteria such as Gardnerella vaginalis, Fannyhessea vaginae, Ureaplasma parvum and members of the Prevotella spp. were significantly enriched in PID cases, while healthy controls were associated with Lactobacillus (L.) crispatus. Quantitative analysis with species-specific quantitative real-time PCR (qPCR) indicated that a high copy number of L. crispatus (measured using calibrated copy estimates by qPCR) was strongly associated with cervical samples from women in the control group, whereas PID cases with this organism had low copies when measured using qPCR. Antibiotic resistance to tetracyclines was more frequently predicted in metagenome-assembled genomes from PID cases, and corresponding isolates cultured from cases were less susceptible to doxycycline (L. iners). Overall, this study supports that PID is associated with cervicovaginal dysbiosis and an absence or low quantity of L. crispatus.
    Keywords:  Lactobacillus; antibiotic; cervical microbiome; dysbiosis; reproductive infection; sexually transmitted infection; vaginal microbiome
    DOI:  https://doi.org/10.1099/mgen.0.001574
  36. Eurasian J Med. 2023 Dec 29. 55(Suppl 1): S1-S8
    Lipid Metabolic Disorders in Neurodegenerative Diseases - Role of Androgen Receptor.
    Satvika Sharma, Avneet Saini, D Dhawan.
      The challenge of managing neurodegenerative disorders is a worldwide concern, especially in the aging population. Neurodegenerative diseases are a varied group of disorders that are characterized by progressive degeneration of the structure and function of the nerve cells. Neurodegenerative diseases are increasing at an alarming rate, and hence there is an urgent need for an in-depth analysis of various metabolic malfunctions that alter the proper functioning of a cell. Lipid metabolism is a process that involves the synthesis and simultaneous degradation of lipids and encompasses a balance that is essential to maintain the structural and functional ability of a cell. Androgen receptor (AR) plays a critical role in regulating cellular functions. Recent studies have expanded our knowledge regarding direct or indirect interactions that occur among mitochondria, peroxisome, and androgen receptors, which play a crucial role in lipid homeostasis. Unusual levels of lipids and cholesterol due to receptor excitation or inhibition are associated with multiple diseases and have been a cause of concern. The androgen receptor, along with other receptors and proteins, forms an important metabolic cascade that, if altered, may cause the accumulation of lipids and result in neurodegenerative disorders. In this review, we underscore the role of the androgen receptor in regulating lipid and cholesterol levels during neurodegenerative disorders (Alzheimers, Parkinson's, multiple sclerosis, and Huntington's disease).
    DOI:  https://doi.org/10.5152/eurasianjmed.2023.23024
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