bims-placeb Biomed News
on Placental cell biology
Issue of 2026–08–30
fourteen papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences
  1. Advancing Human Placental Modeling Through Stem-Cell-Derived Trophoblast Organoids and Reprogramming Innovations.
  2. Sexual Dimorphism in Placental mTORC1 Signaling, Amino Acid Transport, and Mitochondrial Respiration at Term.
  3. Complement Component 1q Deficiency Impairs Maternal Hemodynamic Adaptations to Pregnancy, Decidual Vascular Remodeling, and Fetal Growth in Mice.
  4. Placental changes with assisted reproductive technologies: Insights from the transcriptomic and proteomic profiling of multiple species.
  5. Dysregulated differentiation kinetics underlie the essential role of DNA damage repair in placental development.
  6. Maternal Hypoxia Alters Glucocorticoid Regulation in Adult Female Offspring and Their Embryonic Progeny.
  7. Evolutionary co-option of endogenous retroviruses: syncytins as regulators of placental development and disease.
  8. Third trimester development of the feto-placental vasculature: A computational growth model.
  9. Therapeutic Interventions for Preeclampsia: Integrating Placental and Maternal Perspectives.
  10. Experimental Animal Models of Preeclampsia: Mechanisms, Strengths, and Translational Relevance.
  11. Elevated contractility drives implantation failure in mouse embryos from aged females.
  12. Glycosylated Fibronectin in Fetal Growth Restriction: An Emerging Biomarker of Placental Dysfunction.
  13. Vertical Transmission of Zika Virus: The Immune-Pathophysiological Interface of the Placenta.
  14. Pharmacological mTOR pathway activation does not enhance trophectoderm differentiation in bovine embryos.
  1. Biomedicines. 2026 Jul 31. pii: 1729. [Epub ahead of print]14(8):
    Advancing Human Placental Modeling Through Stem-Cell-Derived Trophoblast Organoids and Reprogramming Innovations.
    Sukanta Jash, John M Sedivy.
      The human placenta is a temporary organ structured to optimize exchange between the maternal and fetal circulatory systems. Its fetal component consists of highly branched chorionic villi, which are anchored to the maternal uterine wall and project into the intervillous space. The outer surface of these villi is lined by a multinucleated, continuous layer called the syncytiotrophoblast, which is supported by an underlying layer of proliferative cytotrophoblast cells and the invasive extravillous trophoblast (EVT). This cellular bilayer forms a selective barrier that directly bathes in maternal blood, allowing for the efficient transfer of oxygen and nutrients while structurally preventing the direct mixing of maternal and fetal blood cells. Human placental studies have been stymied by ethical and accessibility constraints. Stem cell biology has now revolutionized the capacity to model human placental development, in particular with the derivation of human trophoblast stem cells (hTSCs) and organoids. Authentic, self-renewing human trophoblast stem cells (hTSCs) were first derived not from pluripotent stem cells but from primary tissue-first-trimester villous cytotrophoblasts and blastocysts. Derivation from human pluripotent stem cells (PSCs) followed only subsequently, along two principal routes: conversion of naive PSCs, which retain extraembryonic competence, and induction from primed PSCs, as well as by direct reprogramming of somatic cells to induced hTSCs. An important advance underlying these improvements is the mapping of a global reprogramming roadmap. Multi-omic and lineage-tracing experiments have mapped the stepwise transcriptional and epigenetic conversions of fibroblasts to hTSCs, including sequential chromatin reconfiguration, trophoblast gene network activation, and repression of somatic signatures. These results identify major regulatory bottlenecks and intermediate states, improving reprogramming fidelity. The derivation of stem-cell-based trophoblast organoids now enables complex modeling of placental architecture, function, and disease susceptibility in vitro. These organoids accurately recapitulate placental barrier functions and immunological features, allowing for examinations of maternal-fetal health, pregnancy disorders, and placental infection response to viruses like cytomegalovirus and SARS-CoV-2. Looking ahead, the integration of reprogramming and organoid technologies will propel patient-specific and tailor-made models for personalized diagnostics, drug screening, and mechanism studies. As we unravel the molecular ballet of trophoblast induction, such discoveries have the potential to bridge basic translational gaps in reproductive biology and maternal-fetal medicine.
    Keywords:  BMP4–GATA3–TFAP2C signaling axis; human pluripotent stem cells (hPSCs); human trophoblast stem cells (hTSCs); induced trophoblast stem cells (iTSCs); maternal–fetal interface and pregnancy disorders; placenta-on-a-chip/organ-on-chip models; pluripotency-independent reprogramming; syncytiotrophoblast and extravillous trophoblast; trophoblast lineage specification; trophoblast organoids
    DOI:  https://doi.org/10.3390/biomedicines14081729
  2. Antioxidants (Basel). 2026 Aug 06. pii: 977. [Epub ahead of print]15(8):
    Sexual Dimorphism in Placental mTORC1 Signaling, Amino Acid Transport, and Mitochondrial Respiration at Term.
    Hiroshi Shimada, Toshihide Sakuragi, Vincent Zaegel, Anita Kramer, Kristen E Boyle, Theresa L Powell, Thomas Jansson, Fredrick J Rosario.
      Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, evidence for sex-specific differences in placental function remains limited. We hypothesized that placental nutrient-sensing signaling activity, amino acid transport capacity, and mitochondrial respiration are higher in male than female placentas. Placentas were collected from 46 women (BMI 18.5-29.9 kg/m2) with uncomplicated pregnancies delivering appropriate-for-gestational-age infants (n = 23 female; n = 23 male). In homogenates of male placentas, the phosphorylation of S6RP (Ser235/236) was increased and total 4E-BP1 protein expression was reduced compared with female placentas, indicating enhanced mTORC1 signaling. In vitro System A amino acid transport activity was also greater in microvillous plasma membranes isolated from male placentas. Placental mitochondrial respiratory capacity was assessed in villous tissue using high-resolution respirometry with carbohydrate and lipid substrate-uncoupler-inhibitor titration (Carb SUIT and Lipid SUIT) protocols on the Oroboros O2k platform. Male placentas exhibited greater maximal oxidative phosphorylation capacity, enhanced complex II-linked respiration, and higher maximal electron transport system capacity compared with female placentas under both carbohydrate- and lipid-supported respiratory conditions. Although placental weight did not differ between sexes, the birth weight-to-placental weight ratio was significantly higher in male pregnancies, consistent with greater placental functional efficiency. In conclusion, placental mTORC1 signaling activity, System A amino acid transport activity, and mitochondrial respiratory capacity are greater in male than female placentas and are associated with greater placental functional efficiency and fetal growth in male pregnancies.
    Keywords:  fetal growth; human; maternal–fetal exchange; mitochondrial function; nutrient transport
    DOI:  https://doi.org/10.3390/antiox15080977
  3. J Am Heart Assoc. 2026 Aug 27. e048023
    Complement Component 1q Deficiency Impairs Maternal Hemodynamic Adaptations to Pregnancy, Decidual Vascular Remodeling, and Fetal Growth in Mice.
    Evangeline A K Lovell, Stacey J Savin, Amy L Wooldridge, Shanna L Hosking, Lachlan M Moldenhauer, Holly M Groome, Matthew Chapman, Sven Surikow, Laura J Parry, Sarah A Robertson, Alison S Care.
       BACKGROUND: Pregnancy complications such as preeclampsia and fetal growth restriction are caused by compromised placentation associated with impaired maternal cardiovascular and immune adaptation to pregnancy, but the pathophysiological pathways underlying these impairments are not fully defined. C1q (complement component 1q) plays a central role in immune cell recruitment, functional regulation, and immune tolerance. In this study, we investigated the impact of maternal C1q deficiency on maternal uterine and systemic cardiovascular parameters in pregnancy.
    METHODS: C1q null mutant (C1qa-/-) and C57BL/6 wild-type control female mice were mated with BALB/c males. Cardiovascular adaptations were investigated by echocardiography and wire myography, as well as uterine artery ultrasound and decidual spiral artery assessment.
    RESULTS: C1qa-/- dams exhibited increased fetal loss (↑3.6-fold; P=0.011) and late gestation fetal growth restriction, notably among male fetuses (P=0.002). Mesenteric arteries from C1qa-/- dams displayed heightened vasoconstriction ex vivo (area under the curve ↑34%; P=0.018). In midpregnancy, C1qa-/- dams exhibited uterine artery dysfunction (resistance index ↑23%; P=0.014), defective decidual spiral artery remodeling (vessel wall thickness: ↑16%; P=0.010), and reduced decidual perivascular macrophages surrounding spiral arteries (↓28%; P=0.050) compared with control dams.
    CONCLUSIONS: These findings indicate that maternal C1q deficiency disrupts key cardiovascular adaptations to pregnancy, likely contributing to poor fetal outcomes via impaired maternal hemodynamics and constrained placental function. This study identifies maternal C1q as a critical regulator of pregnancy-induced vascular adaptation and supports mounting evidence for C1q relevance in pregnancy complications involving placental insufficiency.
    Keywords:  complement C1q; fetal growth restriction; placental insufficiency; pregnancy; vascular adaptation
    DOI:  https://doi.org/10.1161/JAHA.125.048023
  4. J Anim Sci. 2026 Aug 28. pii: skag274. [Epub ahead of print]
    Placental changes with assisted reproductive technologies: Insights from the transcriptomic and proteomic profiling of multiple species.
    Stacia C Hickey, Neha Mishra, Molly S Kornfield, Lisa A Vrooman.
      Assisted reproductive technology (ART), such as in vitro fertilization (IVF), is used to treat infertility in humans, in agriculture for animal production, and in wildlife preservation efforts. In humans, ART is known to be associated with increased risks and adverse outcomes in pregnancy for both mother and offspring, likely due to changes in placental development. Research using animal models as well as human tissue offers the opportunity to examine what placental changes are present in ART pregnancies to better understand the etiology of ART effects on pregnancy. Promising directions in research include both transcriptomic and proteomic studies to elucidate how specific gene and signaling pathways in the placenta may be altered with ART. This may allow us to develop treatment options to make ART pregnancies safer and more efficient. In this review of the literature, we will discuss the current knowledge from transcriptomic and proteomic studies of ART placentas in both animal and human pregnancies.
    Keywords:  assisted reproductive technologies; placenta; proteomics; transcriptomics
    DOI:  https://doi.org/10.1093/jas/skag274
  5. Nat Commun. 2026 Jul 22. pii: 8944. [Epub ahead of print]17(1):
    Dysregulated differentiation kinetics underlie the essential role of DNA damage repair in placental development.
    Shanshan Yi, Mingzhu Wang, Qianshu Zhu, Yanxin Huang, Jing Xiao, Ming Zong, Wenju Liu, Xingyi Zhou, Jincan He, Mian Wang, Kexin He, Xiaochen Kou, Yanhong Zhao, Hong Wang, Rui Gao, Shaorong Gao, Guang Yang, Jiayu Chen, Cizhong Jiang.
      The placenta orchestrates maternal-fetal exchanges, and its dysfunction compromises pregnancy outcomes. Somatic cell nuclear transfer (SCNT) placentas offer a model to investigate such dysfunction. However, SCNT placentas exhibit severe pathological features that remain poorly understood. Using single-nucleus multi-omics profiling, we uncover defective differentiation programs in SCNT placentas, including the persistent multipotency of arrested trophoblast precursors and an aberrant differentiation trajectory in the junctional zone. In addition, SCNT placentas demonstrate impaired VEGF signaling, which subsequently compromises labyrinthine vascularization. Mechanistically, we identify reprogramming-induced DNA damage as a core driver of these defects. Furthermore, we trace this genomic instability to the loss of donor cell-inherited H3K27me3 protection, an epigenetic deficiency that correlates with specific DNA damage-associated regions. Consistently, enhancing DNA damage repair pathways restores proper trophoblast differentiation kinetics and vascular transport capacity. Collectively, our study reveals that genomic instability acts as a barrier to placental development, providing a molecular framework to understand compromised placental function.
    DOI:  https://doi.org/10.1038/s41467-026-75623-3
  6. Dev Neurosci. 2026 Aug 24. 1
    Maternal Hypoxia Alters Glucocorticoid Regulation in Adult Female Offspring and Their Embryonic Progeny.
    Sofiya Potapova, Ekaterina Tyulkova, Oleg Vetrovoy.
       INTRODUCTION: Prenatal hypoxia is a clinically relevant adverse factor that may affect fetal development both directly and through activation of maternal glucocorticoid signaling. The placenta plays a central role in this process by regulating fetal exposure to maternal glucocorticoids, yet it remains unclear whether hypoxia-induced endocrine alterations can extend into the next generation and modify placental and fetal brain glucocorticoid regulation during embryogenesis. Here, we investigated whether maternal hypoxia programs the glucocorticoid phenotype of adult female offspring and whether this phenotype is associated with altered placental glucocorticoid signaling and fetal brain corticosterone exposure in their progeny.
    METHODS: Adult female rats prenatally exposed to maternal hypoxia (MH) were examined for 24-h plasma corticosterone rhythms. These females were then mated with control males, and embryonic tissues from their progeny (progeny of maternal hypoxic females, PMH) were collected at e14, e16, e18, and e20. Corticosterone concentrations were measured in amniotic fluid and fetal brain, whereas placental and fetal brain expression of glucocorticoid receptor-related genes and 11β-hydroxysteroid dehydrogenases was assessed by qRT-PCR and Western blotting.
    RESULTS: MH females showed overall elevation of plasma corticosterone across the circadian cycle, with a higher fitted MESOR (Midline Estimating Statistic Of Rhythm, i.e. the rhythm-adjusted mean) and reduced rhythmic robustness. In PMH embryos, maternal and fetal placentas (MP and FP) displayed stage- and compartment-specific changes in Nr3c1 and Fkbp5 expression, accompanied by reduced FP Hsd11b2 mRNA at e14, but no change in HSD11B1 and HSD11B2 protein levels in the MP and FP throughout pregnancy. Amniotic fluid corticosterone was increased at e14, e16, and e20, whereas fetal brain corticosterone was elevated at e14 and e16. In fetal brain, Fkbp5 expression increased at e16 and e18, Dusp1 decreased at e20, and Hsd11b1 decreased at e16, whereas GR and HSD11B2 protein levels remained unchanged.
    CONCLUSION: These findings indicate that maternal hypoxia is associated with persistent alteration of glucocorticoid regulation in adult female offspring and with developmental stage-specific remodeling of placental glucocorticoid handling and fetal brain glucocorticoid signaling in the next generation. Therefore, we conducted this pilot study to map circadian corticosterone profiles in female rats exposed to maternal hypoxia and to assess glucocorticoid regulation in their placenta and fetal brain during pregnancy. This approach provided a detailed, temporal understanding of intergenerational glucocorticoid programming.
    DOI:  https://doi.org/10.1159/dne/aclag003
  7. Mol Biol Rep. 2026 Aug 24. pii: 1454. [Epub ahead of print]53(1):
    Evolutionary co-option of endogenous retroviruses: syncytins as regulators of placental development and disease.
    Anamta Gul, Om Saswat Sahoo, Neha Kashyap, Sunil Singh, Anubhuti Rana, Lavanya Gupta, Swati Ajmeriya, Indrani Mukherjee, Ruby Dhar, Nihar R Nayak, Subhradip Karmakar.
      Syncytins are envelope proteins of retroviral origin that have been evolutionarily co-opted to play essential roles in placental biology. Primarily recognized for mediating the fusion of cytotrophoblasts into the syncytiotrophoblast, a multinucleated epithelium, critical for nutrient transport and maternal-fetal immune tolerance. Syncytins also contribute to broader aspects of placental development through diverse mechanistic pathways. This review focuses on the evolutionary origins and functional mechanisms of Syncytin-1 (encoded by HERV-W) and Syncytin-2 (encoded by HERV-FRD) in orchestrating placental morphogenesis and homeostasis. We further discuss the clinical significance of aberrant syncytin expression, which is associated with adverse pregnancy outcomes including preeclampsia, intrauterine growth restriction, gestational diabetes mellitus, and trophoblastic disease. Additionally, we examine how exogenous viral infections, such as cytomegalovirus and SARS-CoV-2, may disrupt syncytin transcriptional regulation and compromise placental integrity. Collectively, syncytins represent a paradigm of evolutionary viral domestication, wherein pathogenic genetic elements have been repurposed into indispensable mediators of human reproduction. Their precise spatiotemporal regulation is paramount for optimal placental function and maternal-fetal health. Future research leveraging advanced omics technologies and placental organoid systems will be instrumental in elucidating underlying molecular mechanisms and developing targeted therapeutic interventions for pregnancy-related disorders.
    Keywords:  Gestational pathology; Human endogenous retrovirus; Placental development; Syncytin; Trophoblast fusion
    DOI:  https://doi.org/10.1007/s11033-026-12627-8
  8. Placenta. 2026 Aug 17. pii: S0143-4004(26)00334-6. [Epub ahead of print]183 67-81
    Third trimester development of the feto-placental vasculature: A computational growth model.
    Pascalle Wijntjes, Maureen Groenen, Sjeng Quicken, Myrthe van der Ven, M Beatrijs van der Hout-van der Jagt, Bas B van Rijn, Frans N van de Vosse, Wouter Huberts.
       BACKGROUND: Placental dysfunction is associated with adverse pregnancy outcomes, yet normal placental growth and vascular adaptation remain incompletely understood. Most available data pertain to term placentas, limiting insight into earlier stages of development. This study develops a mathematical framework that conceptualizes potential feto-placental vascular growth between 24 and 40 weeks of gestation in backward fashion. By working backwards from a term placenta, the model provides a systematic approach to simulating placental development and vascular remodeling, enabling hypotheses generation.
    METHODS: A volume-filling algorithm was applied to generate three term placentas: two with central cord insertion (based on ex-vivo and in-vivo geometrical data) and one with marginal cord insertion (based on in-vivo geometrical data). A growth algorithm, incorporating literature-based scaling functions, was applied in reverse to downscale the term vasculature to 24 weeks. Growth was simulated using a reverse sigmoid function for lateral expansion and a linear scale factor for vertical growth, initiated at the cord insertion.
    RESULTS: The model replicated vascular growth trends observed in literature, including a linear increase in umbilical artery diameter and linear vascular volume expansion. Placental topology was influenced by cord insertion, with central insertions producing symmetric growth, while marginal insertions exhibited uneven lateral expansion.
    DISCUSSION: A mathematical framework that conceptualizes feto-placental vascular growth between 24 and 40 weeks of gestation is developed. The framework aligns with existing but scarce data in the literature. Based on these findings, further research directions in vascular versus tissue growth are proposed to deepen our understanding of placental growth, ultimately enhancing the provided model.
    Keywords:  Computational model; Development; Placental growth; Vasculature
    DOI:  https://doi.org/10.1016/j.placenta.2026.08.001
  9. Am J Reprod Immunol. 2026 Aug;96(2): e70299
    Therapeutic Interventions for Preeclampsia: Integrating Placental and Maternal Perspectives.
    Shrreya S Sudade, Luisa Wallentowitz, Emma M Giesen, Evelyn A Huhn, Ann-Christin Tallarek, Sandra M Blois, Stefan Verlohren.
      Preeclampsia (PE), a hypertensive disorder of pregnancy, is one of the leading causes of maternal and fetal mortality worldwide. Beyond the immediate pregnancy impact, it is also associated with increased long-term risks in both the mother and the offspring. Currently, no causal therapy exists. Consequently, the complex and heterogeneous nature of PE necessitates the exploration of novel therapeutic targets to improve maternal and fetal outcomes. This review summarizes models of pathogenesis in PE, particularly the two-stage model of the development of PE, where the placenta is suggested to be the main source of the disease, and the postulation that PE is a result of dysfunction of the maternal cardiovascular system. We explore novel therapeutic approaches, considering the underlying mechanisms such as galectin-13, placental growth factor, therapeutic plasma exchange (TPE), trophoblast-targeted nanomedicine, gene therapy, nitric oxide donors, endothelin receptor antagonists, and mesenchymal stem cells. Challenges in translating preclinical findings to clinical practice, including animal model limitations and ethical considerations, are discussed. Finally, this review integrates current treatment options, discusses their limitations, highlights ethical considerations, and outlines future directions for PE therapeutics, emphasizing the need for personalized therapeutic strategies.
    Keywords:  angiogenesis; immune regulation; maternal–fetal interface; placenta; preeclampsia; therapeutic strategies
    DOI:  https://doi.org/10.1111/aji.70299
  10. Arterioscler Thromb Vasc Biol. 2026 Sep;46(9): e322192
    Experimental Animal Models of Preeclampsia: Mechanisms, Strengths, and Translational Relevance.
    Jane F Reckelhoff, Vladimir Dokic, Denise C Cornelius, Babbette LaMarca, Styliani Goulopoulou, Jessica Faulkner, Jenny L Sones, Mark Santillan, Michael Lin, Jungwei W Fan, Vesna D Garovic.
       CLINICAL PROBLEM: Preeclampsia is a heterogeneous hypertensive disorder of pregnancy characterized by new-onset hypertension and end-organ dysfunction, affecting 5% to 10% of pregnancies globally. It is associated with significant maternal and fetal morbidity and mortality, and delivery remains the only definitive treatment. Understanding the underlying mechanisms is essential for the development of effective therapies.
    RECOMMENDATIONS: Given the heterogeneity of preeclampsia and the absence of a single experimental model that fully recapitulates the human disease, the purpose of this review is to evaluate current animal models of preeclampsia according to the pathophysiological mechanisms they represent. We discuss the strengths, limitations, and translational relevance of these models, identify gaps in the existing experimental framework, and highlight opportunities for future model development and therapeutic discovery.
    SUMMARY: Current models reproduce distinct features of preeclampsia, including abnormal placentation, placental ischemia, angiogenic imbalance, endothelial dysfunction, immune activation, and metabolic dysregulation. Despite mechanistic insights, translational success has been limited. Future progress will depend on mechanism-driven model selections, development of models that better capture early placentation defects and disease heterogeneity, multi-hit approaches, including the incorporation of maternal comorbidities, and integration of human-relevant experimental systems to improve clinical translation.
    DOI:  https://doi.org/10.1161/ATVBAHA.126.322192
  11. Nat Cell Biol. 2026 Aug 25.
    Elevated contractility drives implantation failure in mouse embryos from aged females.
    Kate E Cavanaugh, M J Franco-Oñate, Nicole Horsley, Dilan Gokyer, Tomiris Atazhanova, Diana J Laird, Patrick W Oakes, Joan K Riley, Francesca E Duncan, MaryEllen Pavone, Matteo Molé, Ricard Alert, Orion D Weiner.
      Women in their mid-30s experience a marked decline in fertility. The origin of these fertility defects resides in the implantation capacity of the embryo itself, but the mechanistic basis of this impairment is not well understood. Here we identify a core mechanical defect in embryos from aged females that impairs their implantation competence. Using mouse models, we find that reproductive ageing drives excessive contractility in the trophectoderm, the outer epithelial lineage that enables implantation. This hypercontractility increases blastocyst tissue surface tension and viscosity, which hinders spreading during implantation. Elevated contractility is both necessary and sufficient for age-associated implantation failure. We identify non-invasive imaging signatures that infer embryo mechanics and predict implantation success for embryos of both young and aged females. Analyses of human embryos and in vitro fertilization clinical datasets reveal conserved age-associated mechanical alterations that correlate with implantation potential. Our work implicates embryo mechanics as a key regulator of reproductive longevity.
    DOI:  https://doi.org/10.1038/s41556-026-02052-1
  12. Cureus. 2026 Jul;18(7): e113553
    Glycosylated Fibronectin in Fetal Growth Restriction: An Emerging Biomarker of Placental Dysfunction.
    Dimitrios I Karoutsos, Konstantinos Stefanidis, Lina Michala, Panagiotis Antsaklis, Despoina Mavrogianni, Georgios Asimakopoulos, Georgios Daskalakis.
      Fetal growth restriction (FGR) is a major placenta-mediated pregnancy complication associated with perinatal morbidity, stillbirth, neonatal complications, and long-term cardiometabolic and neurodevelopmental consequences. Its diagnosis remains challenging because fetal smallness alone cannot reliably distinguish constitutionally small fetuses from pathological growth restriction caused by placental insufficiency. Glycosylated fibronectin (GlyFn), a modified extracellular matrix glycoprotein involved in cell adhesion, angiogenesis, endothelial function, and tissue remodeling, has emerged as a promising biomarker of placenta-mediated disease. This review summarizes the biological rationale and current evidence regarding GlyFn in FGR, with emphasis on placental dysfunction, trophoblast invasion, spiral artery remodeling, oxidative stress, endothelial activation, altered angiogenic signaling, and extracellular matrix remodeling. Current data suggest that GlyFn is most consistently associated with preeclampsia, where elevated maternal serum levels have shown diagnostic and prognostic potential. However, direct evidence supporting GlyFn as an independent biomarker of isolated FGR remains limited. Most available findings are derived from preeclampsia cohorts or studies of broader adverse pregnancy outcomes, making it unclear whether GlyFn reflects FGR itself, preeclampsia-related endothelial injury, or general placental stress. GlyFn may be particularly relevant in early-onset placental FGR, where severe malperfusion and endothelial dysfunction are prominent. Its greatest future value may lie in multimarker models combining GlyFn with placental growth factor, soluble fms-like tyrosine kinase-1/placental growth factor ratio, fetal biometry, Doppler indices, and placental histopathology. Prospective longitudinal studies using standardized FGR definitions are required before GlyFn can be translated into clinical practice.
    Keywords:  angiogenic biomarkers; fetal growth restriction; glycosylated fibronectin; placental dysfunction; preeclampsia
    DOI:  https://doi.org/10.7759/cureus.113553
  13. J Immunol Res. 2026 ;2026(1): e6861528
    Vertical Transmission of Zika Virus: The Immune-Pathophysiological Interface of the Placenta.
    Carla de Fátima Silva Menezes, Lívia Carício Martins, Gustavo Batista Ferro, Leticia Vieira Teixeira, Juarez Antônio Simões Quaresma, Pedro Fernando da Costa Vasconcelos, Jorge Rodrigues de Sousa.
      Zika virus (ZIKV) infection represents a critical threat to maternal-fetal health due to its ability to cross the placental barrier, converting this normally protective organ into a direct target of viral infection. This study examines the mechanisms by which ZIKV infects placental cells, including trophoblasts and Hofbauer macrophages, through the engagement of specific cellular receptors such as AXL and T-cell immunoglobulin and mucin (TIM), while simultaneously evading host immune defenses. Although the placental immune system employs interferon signaling and innate immune cells to restrict viral replication, ZIKV disrupts these pathways, promoting chronic inflammation and structural damage within placental tissue. These morphofunctional alterations impair fetal nutrient exchange and facilitate vertical transmission, leading to severe adverse outcomes such as congenital Zika syndrome (CZS), intrauterine growth restriction, and preterm birth. Importantly, pregnancy outcomes appear to depend on a delicate balance between the timing of maternal infection and the effectiveness of the local immune response. Finally, this study highlights the need for advanced molecular approaches and "omics" technologies to address existing knowledge gaps regarding viral variability and to inform the development of future therapeutic strategies aimed at preventing fetal transmission.
    Keywords:  Zika virus infection; placental circulation; vertical transmission
    DOI:  https://doi.org/10.1155/jimr/6861528
  14. Reprod Biol. 2026 Aug 25. pii: S1642-431X(26)00106-3. [Epub ahead of print]26(4): 101284
    Pharmacological mTOR pathway activation does not enhance trophectoderm differentiation in bovine embryos.
    Mirela Soares Vilioti, Beatriz Cartaxo Ragnelli, Francieli Perroni Berling, Camilla Mota Mendes, Mayra Elena Ortiz D'Ávila Assumpção, Marcelo Demarchi Goissis.
      The formation of the blastocyst is a highly orchestrated process involving different cellular and molecular aspects. In mice, the mTOR pathway influences the Hippo pathway, leading to expression of trophectoderm (TE)-related genes. However, these mechanisms are not fully characterized in bovine embryos, and biological pathways are not always conserved across species. We hypothesized that mTOR pathway positively influences the TE differentiation in bovine embryos. This study aimed to evaluate the effects of the mTOR agonist MHY1485 (MHY) on TE formation in in vitro-produced bovine embryos. Embryos were treated at 96 h post insemination (hpi) with 2 µM MHY or DMSO (vehicle) until 144 hpi or 192hpi. At 144 hpi, morulae were collected for gene expression analysis of CDX2, GATA3, OCT4, SOX2, TFAP2C and YAP1. No significant differences in mRNA expression were observed between the Control, DMSO or MHY groups. At 192 hpi, embryos were fixed for confocal microscopy to assess the TE marker GATA3 and the Hippo-related transcription factor YAP1. While total cell and inner cell mass counts remained unaffected, TE cell numbers were significantly reduced in the DMSO group compared to both the Control and MHY groups. Furthermore, nuclear YAP1 intensity was lower in the DMSO group compared to the MHY group, in which YAP1 was lower than the Control. In conclusion, pharmacological activation of the mTOR pathway did not positively influence TE differentiation in bovine embryos; however, it effectively rescued the unexpected negative effects induced by the vehicle (DMSO) on TE cell number and YAP1 signaling.
    Keywords:  Blastocyst; DMSO; Hippo pathway; Inner cell mass
    DOI:  https://doi.org/10.1016/j.repbio.2026.101284
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