bims-placeb 2026-05-31 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2026–05–31
seventeen papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

Functional heterogeneity in trophoblast stem cells derived from recurrent pregnancy loss products of conception.
The human placenta development and anatomy.
Transcriptional Control by FOXO4 Regulates Trophoblast Differentiation and Safeguards Placental Development Through MITD1- and PCBP2-Mediated Redox Homeostasis.
Engineering the human placenta: Advances in modeling placental function.
Epigenetic regulation of non-coding DNA in placental development and disorders.
FNDC5 deficiency alters placental development, maternal body weight, and fetal-placental growth in mice.
Semaglutide Induces Oxidative Stress and Differentially Modulates mTOR-Dependent Growth and Invasion in Human Trophoblast Cell Models: Implications for Placental Function.
Effects of Maternal Obesity on Fetal Cerebral Glucose Transporter Expression.
Fetal-Fetal and Fetal-Maternal Microchimerism: Insights from Mammalian Placental Biology.
Aberrant expression of Gremlin1 induces trophoblast senescence in the placenta of advanced maternal age pregnancy.
Placental Extracellular Vesicles Inhibit the Progression of Endometriosis by Inducing Ferroptosis.
Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation.
Viral threats to pregnancy: Global health risks in the era of pandemics.
Decidualization potential of endometrial mesenchymal stem cells and their role in reproductive health.
Genetically predicted cytotrophoblast gene expression is associated with birth weight and adult body mass index.
Could aspirin be both a protective factor and a factor promoting placental abruption?
Long-Term Endurance Exercise Confers Cardioprotection against Metabolic Distress in Obese Type 2 Diabetic Female Mice without Bodyweight Loss.

Mol Hum Reprod. 2026 May 29. pii: gaag033. [Epub ahead of print]

Functional heterogeneity in trophoblast stem cells derived from recurrent pregnancy loss products of conception.

Qi Fu, Keisuke Kozai, Xingrao Ke, Joseph M Varberg, Sheng Xia, Ashley S Howard, Michael Lydic, Kristin Holoch, Courtney Marsh, Elin Grundberg, Kaela M Varberg.

  Recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages, affects 1-5% of couples attempting to conceive and most frequently occurs between 6 and 8 weeks of gestation, coinciding with critical stages of placental development. Despite this temporal association, placental contributions to RPL pathogenesis remain poorly understood. We hypothesized that trophoblast lineage development, including extravillous trophoblast (EVT) and syncytiotrophoblast (STB) differentiation, are disrupted in RPL. To test this hypothesis, we established and functionally characterized human trophoblast stem (TS) cell lines derived from products of conception (POC) obtained from consenting idiopathic RPL cases. Four TS cell lines were successfully derived from five POC samples, representing both normal and abnormal karyotypes. All established TS cell lines exhibited canonical stem-state trophoblast features, including epithelial morphology, ELF5 promoter hypomethylation, expression of trophoblast-specific microRNAs, and trophoblast marker expression. Despite this preserved identity, TS cell lines displayed marked heterogeneity in proliferation and differentiation capacity. TS cells derived from POC with abnormal karyotypes exhibited prolonged doubling times and impaired differentiation, while those from normal karyotypes more closely resembled cytotrophoblast-derived control TS cells. Although all TS cells formed morphologically comparable STB spheroids, functional deficits in human chorionic gonadotropin β secretion were observed in a cell-line specific manner. EVT differentiation capacity varied substantially across POC-derived TS cell lines. Transcriptomic analyses revealed karyotype-associated transcriptional heterogeneity, including enrichment of senescence- and cell cycle-associated pathways across subsets of POC-derived TS cell lines. Together, these findings demonstrate that patient-specific TS cell lines retain trophoblast identity yet exhibit meaningful functional heterogeneity that becomes evident upon differentiation, underscoring the importance of functional validation in newly established in vitro placental cell lines. Overall, POC-derived TS cells are a powerful platform for investigating molecular mechanisms underlying RPL.

Keywords:  cellular senescence; placental development; products of conception (POC); recurrent pregnancy loss (RPL); trophoblast differentiation; trophoblast stem cells

DOI:  https://doi.org/10.1093/molehr/gaag033
Arch Gynecol Obstet. 2026 May 28.

The human placenta development and anatomy.

Dorcas Quaye, Peter Ofori Appiah, Dorotheah Obiri, John Ahenkorah, Kwame Adu-Bonsaffoh.

  The human placenta is a specialized fetomaternal organ whose architecture evolves throughout pregnancy. Its development begins with implantation, followed by the differentiation of trophoblast lineages that establish the early villous structures and mediate subsequent exchange between the maternal and fetal circulations. By the end of the second trimester, coordinated remodeling of villous stroma, vasculature, and syncytium transforms the placenta into a highly specialized interface capable of meeting the growing demands of pregnancy. Despite extensive research in this area, most developmental accounts emphasize early morphogenesis, leaving the structural transitions of mid- and late gestation underexplored These later phases are critical for understanding how architectural specialization supports placental function and how deviations in these processes underpin pregnancy complications. This review synthesizes current understanding of placental morphogenesis and histomorphology across gestation. It integrates classical placental histology findings with recent advances in three-dimensional imaging, lineage tracing, and vascular modeling. By combining developmental and structural perspectives, this review offers an updated understanding of how the architecture of the placenta evolves to sustain pregnancy.

Keywords:  Histomorphology; Implantation; Placenta; Syncytium; Villous structure

DOI:  https://doi.org/10.1007/s00404-026-08382-7
FASEB J. 2026 Jun 15. 40(11): e71971

Transcriptional Control by FOXO4 Regulates Trophoblast Differentiation and Safeguards Placental Development Through MITD1- and PCBP2-Mediated Redox Homeostasis.

Priyanka Das, Rupasri Ain.

  Forkhead box O4 (FOXO4) is highly expressed in the placenta, but its molecular role in trophoblast biology remains unclear. Transcriptomic analysis of human placenta revealed FOXO4 abundance, prompting investigation of its function in trophoblast differentiation and placental development. We found that FOXO4 expression is induced during mouse trophoblast stem (TS) cell differentiation. Gain- and loss-of-function studies demonstrated that FOXO4 promotes differentiation of TS cells towards the trophoblast giant cell (TGC) lineage. Chromatin immunoprecipitation sequencing (ChIP-seq) identified FOXO4 binding to promoters of genes involved in cell cycle regulation, epigenetic modification, metabolism, and ferroptosis. Among these, MITD1 and PCBP2 emerged as key downstream effectors mediating ferroptosis resistance. FOXO4 knockdown enhanced lipid peroxidation and ferroptotic cell death, whereas FOXO4 overexpression upregulated MITD1 and PCBP2 and restored cell viability. Similar protective effects were observed in human JEG-3 trophoblast cells, indicating conservation of FOXO4's function across species. In vivo, FOXO4 expression was elevated in invasive trophoblast cells of E14.5 mouse placenta, whereas FOXO4, MITD1, PCBP2, and GPX4 were reduced in human intrauterine growth restriction (IUGR) placentae, consistent with enhanced ferroptosis. Collectively, these findings define FOXO4 as a transcriptional regulator that protects trophoblast cells from ferroptosis via MITD1 and PCBP2, thereby supporting placental development and function.

Keywords:  ChIP sequencing; TGC; differentiation; ferroptosis; intra‐uterine growth restriction

DOI:  https://doi.org/10.1096/fj.202505014RR
Placenta. 2026 Apr 22. pii: S0143-4004(26)00144-X. [Epub ahead of print]

Engineering the human placenta: Advances in modeling placental function.

Aarti Jayul Patel, Karina Vasile, Sien Yee Lau, Jeffery A Goldstein, Colin L Hisey.

  The placenta is a highly specialized organ that mediates nutrient exchange, hormone production, and immune regulation at the maternal-fetal interface. Its dynamic architecture and function throughout gestation present significant challenges in studying placental biology and associated obstetric complications. Emerging developments in bioengineering offer innovative approaches to create physiologically relevant placental models that overcome the constraints of traditional in vitro and in vivo systems. This review highlights progress in microfluidic and organ-on-a-chip systems, spheroid and organoid models, bioengineered scaffolds, and in silico systems. We discuss how these platforms enable the investigation of trophoblast behavior and transport mechanisms and can even mimic the maternal-fetal barrier. By integrating principles of tissue engineering and materials science, advanced in vitro models hold immense promise for advancing our understanding of placental physiology, ultimately informing therapeutic strategies in maternal-fetal medicine.

Keywords:  Cytotrophoblast; Maternal-fetal barrier; Modeling; Organ-on-a-chip; Placenta; Syncytiotrophoblast

DOI:  https://doi.org/10.1016/j.placenta.2026.04.021
Epigenomics. 2026 May 27. 1-14

Epigenetic regulation of non-coding DNA in placental development and disorders.

Ying Hei Kan, Lin Gao, Danny Leung.

  The human placenta is an epigenetically exceptional organ that must execute rapid proliferation, lineage bifurcation, and controlled invasion while maintaining immune tolerance at the maternal-fetal interface. Trophoblast lineages operate within a developmentally programmed "pseudo-malignant" regulatory state, characterized by global DNA hypomethylation, large partially methylated domains, and dynamic chromatin transitions across gestation. This configuration enables transcriptional plasticity but also creates vulnerability to maternal and environmental exposures, which can leave persistent epigenetic effects associated with fetal growth restriction, preeclampsia, preterm birth, and pregnancy loss. Placental health and disease therefore cannot be understood through protein-coding genes alone. The non-coding genome, comprising promoters, enhancers, enhancer-promoter networks, and non-coding RNAs is extensively rewired in trophoblast, with retrotransposons providing a major source of regulatory innovation. Epigenetic mechanisms coordinate these elements to establish trophoblast-specific transcriptional programs, and perturbation at any layer can disrupt differentiation, invasion, endocrine signaling, and immune modulation. Maternal inflammation, hypoxia, toxins, metabolic and psychological stress reshape epigenetically labile non-coding regions, positioning the placenta as both a developmental sensor and molecular archive of the intrauterine environment. Advances in epigenomic profiling highlight the potential of non-coding epigenetic signatures as early biomarkers, while underscoring ongoing challenges in resolving cell-type-specific regulatory programs and accurately annotating repetitive elements.

Keywords:  Placenta; cis-regulatory elements; epigenomics; non-coding DNA; pregnancy complications; retrotransposons

DOI:  https://doi.org/10.1080/17501911.2026.2678924
Sci Rep. 2026 May 25.

FNDC5 deficiency alters placental development, maternal body weight, and fetal-placental growth in mice.

Pinki Nandi, Mavis Lee, Dennis K Lee, Sascha Drewlo.



Keywords:  FNDC5 (Fibronectin Domain Containing 5); Placenta; Preeclampsia; RNA-sequencing; Trophoblast

DOI:  https://doi.org/10.1038/s41598-026-49198-4
Curr Issues Mol Biol. 2026 May 18. pii: 524. [Epub ahead of print]48(5):

Semaglutide Induces Oxidative Stress and Differentially Modulates mTOR-Dependent Growth and Invasion in Human Trophoblast Cell Models: Implications for Placental Function.

Elizabeth Thurmond, Eliza J Roeth, Kristen Noyes, Madeline Boyer, Ethan Evans, Benjamin T Bikman, Paul R Reynolds, Juan A Arroyo.

  Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has transformed obesity and diabetes management. However, its expanding use among reproductive-age women raises concerns about potential effects on early placental development. We examined semaglutide's impact on two human trophoblast cell lines: Swan71 (invasive extravillous) and BeWO (syncytiotrophoblast-like). Cells were treated with semaglutide (100 nM) for 24 h, and proliferation, viability, mitochondrial respiration, oxidative stress, signaling pathways, and invasiveness were evaluated. Semaglutide significantly reduced proliferation in Swan71 cells and increased it in BeWO cells, with no significant change in viability for Swan71 and a slight increase for BeWO. Western blot analysis revealed altered phosphorylation of key signaling proteins, including mTOR, p70S6K, 4EBP1, AKT, and ERK, as well as increased AMPK phosphorylation, indicating a shift toward catabolic signaling. Reactive oxygen species (ROS) accumulation increased markedly, accompanied by altered oxygen consumption rates-reduced in Swan71 cells and elevated in BeWO cells. Functionally, semaglutide suppressed Swan71 invasion through Matrigel by approximately three-fold. These findings suggest that semaglutide induces oxidative and metabolic stress in trophoblasts and is associated with altered mTOR-mediated signaling and reduced invasive potential. Such cellular alterations may contribute to compromised placental development and uterine vascular remodeling if exposure occurs near conception. While clinical data remain limited, this study provides mechanistic insight supporting caution in the use of semaglutide during the periconception period and underscores the need for targeted reproductive safety studies.

Keywords:  ROS; invasion; mTOR; mitochondria; semaglutide; trophoblast

DOI:  https://doi.org/10.3390/cimb48050524
bioRxiv. 2026 May 13. pii: 2026.05.11.723868. [Epub ahead of print]

Effects of Maternal Obesity on Fetal Cerebral Glucose Transporter Expression.

Tyler L King, Kevin Prifti, Ruth M Gill, Sarah K England, Antonina I Frolova.

Emerging evidence indicates that the maternal in utero environment has enduring effects on offspring neurodevelopment. The obesity epidemic in the United States affects nearly one-third of women before pregnancy, potentially predisposing offspring to harmful developmental conditions. Glucose, the primary energy source for the brain, is highly regulated by facilitative diffusion glucose transporters (GLUTs). However, our understanding of how maternal obesity influences perinatal cerebral glucose metabolism remains limited. We hypothesized that maternal obesity is associated with altered expression of key GLUTs and dysregulated energy-sensing mechanisms in the fetal brain. Female C57BL/6J mice were randomly assigned to either a control diet (CON) or an obesogenic diet (DIO) (60% kcal from fat, 17.5% kcal from sucrose) for 10 weeks, time-mated with control males, and fed their respective diets throughout gestation. At 18.5 days post coitum, fetal brain tissue was collected for protein analysis. DIO diet did not affect litter size, offspring body weight, or brain weight when compared to CON. Whole brain GLUT1 expression was elevated only in female DIO offspring, while GLUT3 and GLUT4 expression was increased in all DIO offspring without modification by sex. However, maternal diet was not associated with differences in the activation of energy regulatory pathways adenosine monophosphate-activated protein kinase (AMPK) or the nutrient-sensing pathway mechanistic target of rapamycin (mTOR) in the fetal brain. These findings suggest that maternal obesogenic diet alters glucose transporter expression in the fetal brain, indicating a potential disruption in cerebral glucose metabolism during critical periods of perinatal development.

DOI: https://doi.org/10.64898/2026.05.11.723868
J Dev Biol. 2026 Apr 28. pii: 19. [Epub ahead of print]14(2):

Fetal-Fetal and Fetal-Maternal Microchimerism: Insights from Mammalian Placental Biology.

Jorge A De Los Santos Funes.

  Feto-maternal microchimerism (Mc) refers to the exchange of cells between the fetus and mother, and fetal-fetal Mc to the exchange between fetuses during pregnancy. This phenomenon occurs across mammalian species, including humans, mice, and cattle. Key data on Mc cells and theoretical considerations regarding the presence of fetal-derived material, such as trophoblast cells, cell-free fetal DNA (cffDNA), and exosomes in maternal blood are summarized. This review aims to first, synthesize current knowledge on feto-maternal and fetal-fetal Mc across mammals, second, address three core questions: how and where Mc has been demonstrated in animals, what techniques have been used over time to detect fetal-derived material and Mc, and how placental structures influence the frequency of Mc. Finally, it aims to identify gaps in the literature for species such as horses, goats, and pigs. This article concludes that Mc is a widespread phenomenon among mammals, but detection methods and reported frequencies vary significantly by species and placental type. A biological model is presented in this article in which multinucleated trophoblast cells undergo apoptosis, releasing cffDNA that enters the maternal blood circulation after multinucleated trophoblast invasion. Advances in molecular biology technology have improved the ability to detect fetal-derived material, cells, DNA, and exosomes in maternal blood. However, notable research gaps remain for Mc in horses, goats, and pigs, highlighting the need for targeted studies to better understand species-specific patterns or a general biological model.

Keywords:  cell-free fetal DNA; fetal; maternal plasma; microchimerism; multinucleated cells; placenta; pregnancy; trophoblast

DOI:  https://doi.org/10.3390/jdb14020019
J Transl Med. 2026 May 27.

Aberrant expression of Gremlin1 induces trophoblast senescence in the placenta of advanced maternal age pregnancy.

Haojun Tian, Yingying Wei, Lu Zhang, Xuancheng Wei, Mengtian Wei, Ruixue Wang, Qizhi He, Tao Duan, Xiaojie Huang, Kai Wang.

   BACKGROUND: The global incidence of advanced maternal age (AMA) has risen substantially over the past two decades, accompanied by elevated risks of adverse perinatal outcomes. This phenomenon has been linked to premature placental aging, yet the precise molecular pathways have yet to be fully elucidated. Our study aims to delineate the impact of Gremlin1 (GREM1) aberrant expression in AMA pregnancies and elucidate its underlying molecular mechanisms.
METHODS: This study employed a multi-level approach to investigate GREM1's role in AMA-associated placental aging. Analysis of 42 human placental samples quantified GREM1 expression patterns. In vitro functional validation was performed using the HTR-8/SVneo trophoblast cell through GREM1 overexpression/knockdown interventions, assessing proliferation, migration, and invasion capabilities, as well as senescence through the expression of key markers and senescence-associated β-galactosidase staining. Mechanistic studies examined GREM1-BMP4 interactions and SMAD1/5/9 phosphorylation via Western blotting, supplemented by rescue experiments with exogenous BMP4 and BMP-SMAD pathway activator sb4. In vivo validation utilized AAV9-mediated GREM1 overexpression in pregnant mice, with placental aging phenotypes evaluated following sb4 intervention.
RESULTS: First-time identification revealed significant GREM1 upregulation in human AMA placentas. Cellular experiments demonstrated GREM1 overexpression suppressed trophoblast proliferation, migration, and invasion while inducing senescence, effects that were ameliorated by GREM1 knockdown. Mechanistically, GREM1 promoted senescence by antagonizing BMP4 and inhibiting SMAD1/5/9 phosphorylation. Both BMP4 and sb4 partially rescued senescence phenotypes in vitro. Animal studies confirmed AAV9-GREM1 induced premature placental aging and reduced placental efficiency in mice, phenotypes significantly alleviated by sb4 treatment. In naturally aged AMA mice, sb4 treatment mitigated molecular senescence markers but did not significantly improve macroscopic pregnancy outcomes.
CONCLUSION: This work elucidates GREM1/BMP4 imbalance-driven trophoblast senescence as one of the mechanisms underlying AMA-related placental dysfunction, mediated through impaired BMP-SMAD signaling. While targeting this axis effectively mitigates molecular aging markers, the multifaceted nature of clinical AMA suggests that fully reversing macroscopic outcomes may require integrated, multi-pathway interventions. Nevertheless, targeted modulation of the BMP-SMAD pathway or anti-GREM1 strategies holds significant clinical intervention potential.

Keywords:  Advanced maternal age (AMA); Aging; GREM1; Placenta

DOI:  https://doi.org/10.1186/s12967-026-08311-x
Am J Reprod Immunol. 2026 May;95(5): e70256

Placental Extracellular Vesicles Inhibit the Progression of Endometriosis by Inducing Ferroptosis.

Minghui Qin, Chunqin Chen, Yue Wu, Lin Wang, Qi Chen, Min Zhao.

   BACKGROUND: Endometriosis (EMs) is an estrogen-dependent chronic inflammatory disease, and its pathogenesis remains unclear. Although the placenta is an organ with tumor-like characteristics, its development, including its invasive function, is tightly controlled. One of the mechanisms is that extracellular vesicles (EVs) released by the placenta play an important role in this regulation. Placental extracellular vesicles carry functional proteins and regulatory RNAs. Our previous studies reported that placental extracellular vesicles inhibit the growth of ovarian cancer and cervical cancer both in vitro and in vivo. In recent years, ferroptosis, a novel form of cell death driven by iron-dependent lipid peroxidation, has been found to play a key role in the development of EMs.
METHODS: Extracellular vesicles (EVs) derived from the placenta were isolated and identified, and their morphology and size distribution were characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA).In vitro experiments were conducted using endometriosis cells as a model. Cell viability was assessed using the CCK-8 assay. The expression of the ferroptosis-related molecules GPX4 and SLC7A11 was detected by Western blot and qRT-PCR, while lipid peroxidation and oxidative stress were evaluated by measuring malondialdehyde (MDA) and reactive oxygen species (ROS) levels. In addition, the ferroptosis inhibitor Ferrostatin-1 (Fer-1) was used for intervention experiments to verify the role of ferroptosis in this process. Potential miRNAs were further predicted using bioinformatic databases, and the regulatory mechanism was validated through miRNA transfection experiments, dual-luciferase reporter assays, and SLC7A11 overexpression rescue experiments. In vivo, a mouse model of endometriosis was established to evaluate the effect of EVs on the growth of ectopic lesions.
RESULTS: The current study demonstrated that placental EVs delivered miRNA-26a-5p, which downregulated SLC7A11, led to increased lipid peroxidation and triggered ferroptosis, and ultimately inhibited the progression of endometriosis. Fer-1 effectively reversed these effects. In vivo, placental EVs significantly reduced ectopic lesion volume in mice.
CONCLUSION: This study revealed that placental EVs induced ferroptosis through miRNA-26a-5p/SLC7A11-GPX4 axis, providing a potential therapeutic target for endometriosis.

Keywords:  SLC7A11; endometriosis; ferroptosis; miRNA‐26a‐5p; placental extracellular vesicles

DOI:  https://doi.org/10.1111/aji.70256
Biomolecules. 2026 Apr 23. pii: 628. [Epub ahead of print]16(5):

Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation.

Emily Mazey, Sarah Flannery, Roman Fischer, Neva Kandzija, Wei Zhang, Yuma Yamada, Manabu Tokeshi, Errin Johnson, Naveed Akbar, James Bancroft, Fadil M Hannan, Manu Vatish.

  Targeted delivery systems offer a promising approach for selectively modulating cellular processes; yet the intracellular consequences of targeted nutrient delivery to trophoblast cells remain poorly defined. Here, we investigated a previously validated placenta-targeting peptide conjugated to liposomes encapsulating stable isotope-labelled L-arginine and L-lysine to examine cellular uptake and downstream molecular responses in a trophoblast-like cell model. Peptide-dependent uptake of fluorescently labelled liposomes was confirmed in BeWo cells, demonstrating selective internalisation compared with non-targeted controls. Encapsulation of isotope-labelled amino acids enabled direct quantification of intracellular delivery and incorporation into the cellular proteome using stable isotope labelling by amino acids in cell culture (SILAC). Quantitative proteomic analysis revealed coordinated changes in proteins associated with translation, metabolism, and nitric oxide synthase regulation following targeted liposomal uptake. Notably, V-type proton ATPase subunit G1 (ATP6V1G1) and large neutral amino acid transporter small subunit 1 (SLC7A5) showed increased incorporation of labelled amino acids and were independently validated by Western blotting. Together, these findings establish a proof-of-concept platform for targeted intracellular amino acid delivery to trophoblast-like cells and define the resulting proteomic responses. This work provides mechanistic insight into intracellular amino acid utilisation and a framework for future studies in placental cell biology.

Keywords:  SILAC proteomics; amino acid delivery; liposomes; placenta-targeted delivery; placental chondroitin sulfate-A-binding peptide (plCSA-bp); quantitative proteomics; trophoblast cells

DOI:  https://doi.org/10.3390/biom16050628
Adv Virus Res. 2026 ;pii: S0065-3527(26)00001-1. [Epub ahead of print]124 1-60

Viral threats to pregnancy: Global health risks in the era of pandemics.

Guilherme M Nobrega, Amit Garg, Jean K Lim.

  Pregnancy represents a uniquely vulnerable period during which viral infections can exert profound effects on maternal health, placental function, and fetal development. Over the past 30 years, emerging and re-emerging viruses, including flaviviruses, coronaviruses, poxviruses, orthomyxoviruses, paramyxoviruses, and filoviruses, have repeatedly demonstrated their capacity to disrupt pregnancy through diverse mechanisms that extend far beyond classical teratogenic outcomes. Nearly every major viral outbreak has revealed a critical gap in our understanding of maternal susceptibility during pregnancy. In this review, we will examine how emerging and re-emerging viruses threaten pregnancy across multiple biological scales, ranging from congenital infection, placental dysfunction, maternal immune dysregulation, and infertility, focusing on modern day viruses from a range of families. Understanding the mechanisms by which reproductive health can be impacted by these viruses and integrating this knowledge in developing care, prevention, and intervention strategies tailored to pregnancy and reproduction should be a foundational part of global health and preparedness.

Keywords:  Coronaviruses; Emerging viruses; Filoviruses; Flaviviruses; Maternal-fetal interface; Orthomyxoviruses; Paramyxoviruses; Placental cell tropism; Poxviruses; Pregnancy; Re-emerging viruses; Reproductive health; Vertical transmission; Viral pathogenesis; Virus-host interactions

DOI:  https://doi.org/10.1016/bs.aivir.2026.03.001
Reprod Biol Endocrinol. 2026 May 23.

Decidualization potential of endometrial mesenchymal stem cells and their role in reproductive health.

Reyna Peñailillo, Francesca Velarde, Vicente Peragallo-Papic, Ignacio Valenzuela, Mahesh Choolani, Matthew W Kemp, Lara J Monteiro, Sebastian E Illanes.

  The establishment of a successful pregnancy depends on proper embryo development and coordinated endometrial differentiation, particularly through the process of decidualization. Mesenchymal stem/stromal cells (MSCs), especially those derived from endometrial tissue (eMSCs) and menstrual fluid (MenSCs), have emerged as critical players in regulating decidualization, trophoblast invasion, angiogenesis, and immune modulation at the maternal-fetal interface. These cells exhibit potent immunoregulatory functions, underscoring their role in establishing a tolerant yet responsive environment for implantation along with promoting angiogenesis and stromal regeneration. Dysfunctional MSCs have been linked to impaired decidualization and pregnancy disorders, including preeclampsia (PE) and fetal growth restriction. Evidence indicates that MenSCs from women with a history of PE exhibit diminished angiogenic potential, impaired trophoblast invasion support, and altered cytokine secretion, associating these alterations to disease pathogenesis. Similarly, aberrant eMSCs contribute to endometriosis by supporting ectopic implantation, impaired decidualization, and enhanced migration.Collectively, these findings highlight the central role of endometrial- and menstrual-derived MSCs in both reproductive success and pathology. They also emphasize their potential as diagnostic biomarkers and therapeutic targets in obstetrics and gynecology. In this review, we summarize current knowledge on the role of endometrial- and menstrual-derived MSCs in pregnancy establishment and related complications, and discuss their emerging promise as diagnostic tools and therapeutic strategies in reproductive medicine.

Keywords:  Decidualization; Endometrium; Mesenchymal stem cells

DOI:  https://doi.org/10.1186/s12958-026-01566-5
Placenta. 2026 May 18. pii: S0143-4004(26)00181-5. [Epub ahead of print]181 201-203

Genetically predicted cytotrophoblast gene expression is associated with birth weight and adult body mass index.

Alyssa C Parker, Alison J Eastman, Phillip Lin, Jing Wang, James Jaworski, Rebecca Sale, Catherine A Greene, Eric R Gamazon, Elizabeth A Jasper, Jacklyn N Hellwege, David M Aronoff, Todd L Edwards, Digna R Velez Edwards.

  Invasion of fetal placental cytotrophoblasts into the maternal endometrium affects fetal growth and birth weight, which are associated with metabolic disease risk later in life. We hypothesized that cytotrophoblast gene expression patterns are associated with birth weight and adult body mass index. To evaluate this hypothesis, we sequenced cytotrophoblast DNA and RNA from 44 placentas and trained a gene expression imputation model. We then performed transcriptome-wide association studies and found one gene associated with birth weight and 11 genes associated with adult body mass index. These findings highlight the significance of cytotrophoblasts in metabolic disease risk later in life.

Keywords:  BMI; Birth weight; Cytotrophoblasts; Placenta; TWAS

DOI:  https://doi.org/10.1016/j.placenta.2026.05.019
J Obstet Gynaecol Can. 2026 May 26. pii: S1701-2163(26)00206-9. [Epub ahead of print] 103404

Could aspirin be both a protective factor and a factor promoting placental abruption?

Emmanuel Bujold, Kypros H Nicolaides.

  Placental abruption is associated with deep placentation disorders and linked to preeclampsia. We aimed to clarify its association with aspirin. Since the prophylactic use of aspirin at 150-162 mg daily from 11-14 weeks prevents most cases of preterm preeclampsia, one might think that it also prevents placental abruption. However, the literature is not so clear, and aspirin may even increase this risk. Additional studies are needed, but it is certainly important to limit aspirin to women who are truly at risk of preeclampsia and to consider randomized trials to evaluate the possibility of reducing or even stopping aspirin at the end of the second trimester.

Keywords:  Aspirin; Placental Growth Factor; Placental abruption; Preeclampsia; Pregnancy; Prenatal screening

DOI:  https://doi.org/10.1016/j.jogc.2026.103404
Med Sci Sports Exerc. 2026 May 27.

Long-Term Endurance Exercise Confers Cardioprotection against Metabolic Distress in Obese Type 2 Diabetic Female Mice without Bodyweight Loss.

Joungbo Ko, Eunhee Chung, Ludmila Cosio-Lima, Armaghan Mahmoudian, Youngil Lee.

   INTRODUCTION: Endurance exercise (EXE) has been recognized as a cardioprotective strategy against metabolic diseases, including obesity and type 2 diabetes. However, the precise molecular mechanisms remain incompletely understood, especially in female populations. This study investigates the molecular metabolic signaling nexus in a female mouse model of obese type 2 diabetes (OT2D) induced by a high-fat diet (HFD) and a single dose of streptozotocin (STZ).
METHODS: Female mice (n=31) were assigned into three groups: a normal diet control (CON, n=11), HFD+STZ (n=11), and HFD+STZ + a 15-week treadmill exercise (HFD+STZ+EXE, n=11). Left ventricles were collected 90 minutes after the last EXE session for analyzing key molecular signaling pathways, mitochondrial function, autophagy/mitophagy, and apoptosis.
RESULTS: EXE significantly reduced hyperglycemia and cell death, independent of body weight changes and enhanced cardiac insulin signaling (IR β , PI3K, and AKT) and restored GLUT4 levels. Also, EXE increased protein expression of lipolysis-related proteins (p-PKA, ATGL, and ABHD5) and beta-oxidation-related proteins (ACADVL and HADHSC). Intriguingly, this coincided with a remarkable increase in intramyocardial lipid content (myocardial steatosis) concomitant with de novo lipogenesis (ACSS2, reduced p-ACC via PP2A activation, DGAT upregulation). Despite myocardial steatosis, EXE restored OT2D-induced mitochondrial respiratory dysfunction by downregulating uncoupling protein 3 (UCP3). Moreover, EXE-induced cardioprotection was associated with improved autophagy/mitophagy; The mitophagy was linked to the restoration of the mitochondrial fission protein DRP1.
CONCLUSIONS: These findings demonstrate that weight loss is not a prerequisite for EXE-induced cardioprotection in OT2D females. The benefits arise from a multifaceted adaptive network involving improved metabolic signaling, mitochondrial function, and cellular quality control.

Keywords:  APOPTOSIS; AUTOPHAGY; ENDURANCE EXERCISE; HYPERGLYCEMIA; LIPID METABOLISM; MITOCHONDRIA; MITOPHAGY

DOI:  https://doi.org/10.1249/MSS.0000000000004036