bims-placeb 2026-09-13 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2026–09–13
twelve papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

Hippo signaling regulates spontaneous human trophoblast syncytialization in three-dimensional cultures.
Heterologous cell-cell junctions support transepithelial endometrial trophoblast invasion in human.
The maternal-to-zygotic transition is a critical window for PFOA-induced disruption of developmental programming.
Exosomes-mediated molecular mechanisms underlying the transformation of ovarian tissue into a functional placental analogue in black rockfish ( Sebastes schlegelii).
Single-cell transcriptomics on FFPE placenta: A novel method for comprehensive exploration of an entire placental section.
Postpartum cardiac structure and organ homeostasis following regulatory T cell depletion in early pregnancy.
Machine Learning and Functional Analysis of Placental DNA Methylation Signatures for Early-Onset Preeclampsia.
Spatially ordered zygotic genome activation fulfills embryo quality control.
Fetal growth as an integrated maternal-placental-fetal system: What evidence can explain.
Altered Expression of Energy Metabolism-Related Genes in Placental Trophoblast Cells in Preeclampsia.
Prenatal exposure to wildfire fine particulate matter and fetal growth outcomes in the United States: Findings from the ECHO Cohort.
In vitro oocyte maturation is associated with altered OCT4 promoter methylation, DNMT expression, and early embryonic development in transgenic mouse embryos.

Mol Hum Reprod. 2026 Sep 08. pii: gaag054. [Epub ahead of print]

Hippo signaling regulates spontaneous human trophoblast syncytialization in three-dimensional cultures.

Michael Zheng, Lin Zhao, Richard Xi, Jahdiel DeNobrega, Mary Tammo, Stephen J Renaud, Peeyush K Lala.

  Proper trophoblast development is essential for placental function and is a key determinant of pregnancy outcomes. Three-dimensional spheroid and organoid cultures using cells from placental tissues or trophoblast stem cells have emerged as models that recapitulate cell-cell interactions and aspects of the physiological environment. Trophoblast organoids typically contain self-renewing cytotrophoblasts located toward the periphery in contact with basement membrane, whereas cells within the core fuse into hormone-producing syncytiotrophoblast. Removing cells from matrix and/or culturing them in suspension can reverse this organization. In both cases, spontaneous syncytialization occurs, but the underlying mechanisms remain poorly understood. To identify signaling pathways associated with spontaneous trophoblast differentiation in three-dimensional conditions, human trophoblast stem cells were either maintained in the stem state as two-dimensional (2D) monolayers or aggregated in suspension without an exogenous matrix to form three-dimensional cultures. Expression and localization of trophoblast subpopulation markers were compared between two- and three-dimensional cultures. Three-dimensional cultures displayed increased spontaneous differentiation into the syncytiotrophoblast lineage along the periphery, accompanied by reduced proliferation of cytotrophoblasts. Consistent with this observation, BeWo choriocarcinoma cells exhibited increased chorionic gonadotropin levels in three-dimensional culture, whereas this response was not observed in HTR8/SVneo immortalized trophoblasts. Gene expression and pathway enrichment analyses identified Hippo signaling as altered in three-dimensional trophoblast stem cell cultures, with reduced expression of several genes associated with YAP1/TAZ-TEAD transcriptional activity. Inhibition of LATS1/2, which activates YAP1/TAZ-TEAD signaling, reduced spontaneous syncytiotrophoblast formation. These findings suggest that reduced YAP1/TAZ-TEAD activity may facilitate self-organized syncytialization in three-dimensional trophoblast cultures.

Keywords:  3D culture; Hippo signaling; YAP1/TAZ; human placenta; organoid; syncytiotrophoblast; trophoblast differentiation; trophoblast stem cells

DOI:  https://doi.org/10.1093/molehr/gaag054
Mol Hum Reprod. 2026 Sep 09. pii: gaag053. [Epub ahead of print]

Heterologous cell-cell junctions support transepithelial endometrial trophoblast invasion in human.

Liubov Izmaylova, Eva Miriam Buhl, Irmgard Classen-Linke, Benjamin Rösing, Rudolf E Leube.

  The first step of embryonic trophoblast invasion involves penetration of the endometrial epithelium, which is a unique biological process involving the junction-free apical surfaces of two distinct epithelia. Although cell-cell junctions have been shown to play a role in the establishment of endometrial receptivity, data on their role in the invasion process are lacking. To examine whether human transepithelial trophoblast invasion is linked to heterologous junction formation between trophoblast and endometrial epithelial cells, we used a three-dimensional in vitro implantation model. Hybridoma-derived AC-1M88 extravillous trophoblast spheroids of defined size (300 µm) were placed either on endometrial adenocarcinoma-derived Ishikawa monolayers or on biopsy-derived primary endometrial epithelial cell monolayers. Labelling trophoblast and endometrial cells with different fluorescent dyes allowed differentiation of the two cell populations and monitoring of the invasion process for up to two days after attachment. Trophoblast invasion was tracked by fluorescence microscopy and quantified with the help of image analysis tools. We observed collective transepithelial invasion of the trophoblast into the endometrial monolayers. Junction formation was then assessed by transmission electron microscopy and immunofluorescence microscopy. We observed that transepithelial trophoblast invasion was accompanied by de novo formation of tight junctions, adherens junctions and desmosomes between trophoblast and endometrial cells. The relevance of desmosomal adhesion for invasion was furthermore examined by using blocking antibodies against the desmosomal cadherin desmoglein 2. We could demonstrate that the blocking antibodies stalled the invasion process. Together, we conclude that formation of heterologous cell-cell junctions between trophoblast and endometrial epithelial cells is a robust and important mechanism that facilitates implantation. These findings extend previous studies and offer completely new insights into the functional contribution of cell-cell junction rearrangement to embryo implantation.

Keywords:  AC-1M88 trophoblast spheroids; Ishikawa cells; cell-cell junctions; desmoglein 2; human embryo implantation; primary human endometrial epithelial cells; trophoblast transepithelial invasion

DOI:  https://doi.org/10.1093/molehr/gaag053
Front Cell Dev Biol. 2026 ;14 1887853

The maternal-to-zygotic transition is a critical window for PFOA-induced disruption of developmental programming.

Zainab Afzal, Vandana Veershetty, Evan E Pittman, Charles Hatcher, Deepak Kumar.

  Early embryogenesis is governed by precisely timed gene regulatory programs that coordinate cell fate specification, tissue patterning, and morphogenesis. The maternal-to-zygotic transition (MZT) represents a pivotal developmental milestone during which regulatory control shifts from maternally deposited transcripts to activation of the zygotic genome. Disruption of this transition has the potential to alter developmental trajectories with lasting consequences. Per- and polyfluoroalkyl substances (PFAS), environmentally persistent contaminants, have been linked to developmental abnormalities, yet their impact on core embryonic gene regulatory networks especially with exposure during MZT is not well understood. Using zebrafish (Danio rerio), a tractable vertebrate model and New Approach Methodology (NAM), we investigated how PFAS exposure during the MZT alters early developmental programming. Embryos were exposed starting at different times before and within the MZT time window and collected at 24 h post-fertilization (hpf) for transcriptomic analysis. Targeted qRT-PCR revealed dysregulation of genes controlling transcriptional activation, lineage specification, proliferation, and differentiation. Whole-transcriptome RNA sequencing (RNA-seq) further identified widespread perturbations in gene networks governing transcriptional regulation, cell signaling, and embryonic morphogenesis. Temporal analysis revealed that exposure beginning at 3.5 hpf, followed by 8 hpf, corresponding to early zygotic genome activation and near completion of zygotic activation, respectively, resulted in the greatest differential gene expression changes at 24 hpf. Consistent with these early gene regulatory perturbations, larvae exposed starting at 8 hpf also exhibited altered behavior at 5 days post-fertilization. Together, these findings demonstrate that PFAS exposure during MZT disrupts the establishment of embryonic gene regulatory networks, linking environmental toxicant exposure to altered developmental patterning and organismal outcomes. This work underscores the vulnerability of early developmental transitions to environmental perturbation and positions MZT as a critical window of susceptibility during development.

Keywords:  NAMs (new approach methodologies); PFAS; PFOA; development; maternal-zygotic transition; perfluorooctanoic acid; zebrafish

DOI:  https://doi.org/10.3389/fcell.2026.1887853
Zool Res. 2026 Sep 18. pii: 2095-8137(2026)05-1661-17. [Epub ahead of print]47(5): 1661-1677

Exosomes-mediated molecular mechanisms underlying the transformation of ovarian tissue into a functional placental analogue in black rockfish ( Sebastes schlegelii).

Bing-Yan Zheng, Xiao-Jie Wang, Hai-Shen Wen, Yun Li, Jian-Shuang Li, Xin-Lin Yang, Li-Kang Lyu, Xin Qi.

  Viviparity has independently evolved multiple times in teleosts, leading to diverse modes of maternal nutrient provisioning. In black rockfish ( Sebastes schlegelii), embryos gain dry weight during gestation, supported by a placental connection that facilitates maternal-fetal nutrient transfer. Although prior studies have outlined the morphology and evolutionary convergence of the black rockfish placental analogue, its full architecture and underlying molecular mechanisms remain unresolved. Here, we show that the maternal component of the placental analogue, derived from ovarian follicular tissue, consists of a vascularized outer layer and a glandularized inner layer, organized into a sac-like structure. At the molecular level, this transformation involves epithelial-mesenchymal interactions, angiogenesis, and immune responses. We observed exosome-like structures surrounding the placental analogue and isolated ovarian exosomes for characterization. These findings suggest active crosstalk between developing embryos and the maternal ovary, which may underlie the observed changes. Subsequent proteomic and transcriptomic analyses revealed that these exosomes carry diverse functional cargos, including hepatocyte growth factor b ( hgfb) mRNA. Ovarian cells efficiently internalize exosomes, upregulating hgfb mRNA and protein expression and secretion, which in turn reprograms gene expression and promotes angiogenesis-related placentation. Together, these results elucidate the molecular underpinnings of ovarian placentation in black rockfish and offer valuable perspectives on the oviparity-to-viviparity transition in fish evolution.

Keywords:  Black rockfish; Cell communication; Exosome; Exosome cargo; Placental analogue

DOI:  https://doi.org/10.24272/j.issn.2095-8137.2026.021
Placenta. 2026 Sep 05. pii: S0143-4004(26)00675-2. [Epub ahead of print]183 113-126

Single-cell transcriptomics on FFPE placenta: A novel method for comprehensive exploration of an entire placental section.

Zambiasi Aymeric, Aziza Jacqueline, Clementine Decamps, Emeline Sarot, Carine Valle, Ousselin Jessie, Reboul Hadrien, Courtade-Saidi Monique, Nicaise Yvan, Hamdi M Safouane, Dubucs Charlotte.

   INTRODUCTION: The placenta's complex cellular diversity challenges traditional transcriptomic analyses. Single-cell RNA sequencing (scRNA-seq) offers breakthrough capabilities by enabling transcriptome profiling at the single-cell level. However, traditional scRNA-seq relies on fresh or frozen samples, which present practical storage and quality challenges. Applying scRNA-seq to Formalin-Fixed, Paraffin-Embedded (FFPE) placentas could harness archived samples for clinical insights.
METHODS: We used 10x Genomics Flex technology to analyze 8 non-pathological placentas ranging from 21 + 6 weeks of gestation (WoG) to 39 + 4 WoG.
RESULTS: Our approach identifies diverse cell populations and allows us to discern maternal from fetal cells. Despite sample size limitations, the method yields comparable data to prior fresh/frozen tissue studies and we complete these data by integrating new molecular markers. The potential to correlate single-cell results with histopathology enables us to conduct an in-depth analysis across entire placental sections by concurrently addressing both fetal and maternal cells. We could thus confirm molecular markers like KRT5/6 using immunohistochemistry by revisiting the slide.
DISCUSSION: This innovation could aid in understanding focal anomalies observed on standard histology slides, thereby enhancing traditional histopathological assessments. Given its practicality, integrating our method into routine practice is both feasible and promising.

Keywords:  Differentially expressed genes (DEG); Formalin-fixed Paraffin-embedded (FFPE) placenta; Gene expression profiling; Maternal and fetal cells; Maternal-fetal interface; Non-pathological placenta; Placental transcriptome; Single-cell RNA sequencing (scRNA-seq)

DOI:  https://doi.org/10.1016/j.placenta.2026.09.001
Am J Physiol Heart Circ Physiol. 2026 Sep 10.

Postpartum cardiac structure and organ homeostasis following regulatory T cell depletion in early pregnancy.

Evangeline A K Lovell, Amy L Wooldridge, Shanna L Hosking, Rianna J De Poi, Stacey J Savin, Lisa M Nicholas, Matthew Chapman, Sven Y Surikow, Laura J Parry, Stephane L Bourque, Sarah A Robertson, Alison S Care.

  Maternal insufficiency in regulatory T (Treg) cells in pregnancy impairs maternal-fetal immune tolerance and uteroplacental vascular adaptation. Whether Treg cell insufficiency in pregnancy has maternal postpartum consequences is unknown. Using Foxp3DTR mice, wherein diphtheria toxin (DT) is given to selectively deplete Foxp3+ Treg cells, we investigated whether early pregnancy Treg cell deficiency alters postpartum cardiometabolic outcomes. Transient Treg cell depletion was elicited by DT administration on gestational days 3.5 and 5.5, a protocol that causesdefective decidual uterine spiral artery remodelling, uterine artery dysfunction, elevated fetal loss, and fetal growth restriction. Maternal Treg cell deficiency led to marked alterations in cardiac adaptations at 4-7 weeks postpartum, including reduced left ventricular mass (↓29% end-diastolic and systolic left ventricular mass; both P≤0.024), decreased aortic diameter (↓12%; P=0.004), and increased fractional shortening (↑34%; P=0.042). Constriction responses in the mesenteric arteries and aortae were unchanged. Metabolic parameters and blood pressure were unaffected; however, DT-treated dams exhibited persistent splenomegaly (↑40%; P=0.001) and reduced kidney, uterine, and brain weights (↓7-40%; all P≤0.028). These findings demonstrate that Treg cell insufficiency in pregnancy alters maternal postpartum cardiac structure and organ homeostasis and supports investigation of Treg cell-targeted strategies to improve long-term maternal health.

Keywords:  Treg cells; cardiology; cardiometabolic; postpartum; pregnancy; regulatory T cells; vascular function

DOI:  https://doi.org/10.1152/ajpheart.00374.2026
Reprod Sci. 2026 Sep 10.

Machine Learning and Functional Analysis of Placental DNA Methylation Signatures for Early-Onset Preeclampsia.

Raunak Sharda, Valentina L Kouznetsova, Igor F Tsigelny.

  Early-onset preeclampsia (EOPE) is a pregnancy disorder characterized by abnormal placental development and substantial maternal and fetal risk. DNA methylation at CpG sites has emerged as a key epigenetic mechanism in EOPE. In this study, we developed machine learning models for EOPE classification using β-values from CpG sites in placental tissue. Starting from 599 EOPE-associated CpG sites reported earlier, we used attribute selection in WEKA to identify 30 statistically significant descriptors, which mapped to 19 unique genes. Multiple classifiers were trained and evaluated, and the SPegasos classifier demonstrated the best performance, achieving 95.45% accuracy and an area under the receiver operating characteristic curve of 0.9545 in tenfold cross‑validation, and 95% accuracy in an independent validation dataset. These findings suggest a potentially high correlation between the CpG methylation signatures and EOPE. By creating a machine learning model, we can potentially classify a sample as having EOPE or a normal pregnancy using DNA methylation data at specific CpG sites in placental tissue. Furthermore, we identified the adipogenesis pathway to be central to the disease's pathophysiology. Gain ratio analysis highlighted a subset of CpG sites with particularly strong discriminative power between EOPE and control placentas. Functional annotation of the 19 CpG‑associated genes using protein and pathway enrichment analyses revealed enrichment in signal transduction, steroid and lipid metabolism, and cell developmental processes. Pathway analysis identified adipogenesis as a central pathway, consistent with dysregulated adipokine signaling and systemic inflammation in EOPE. These findings demonstrate that placental CpG methylation signatures can accurately distinguish EOPE from normal pregnancies and provide mechanistic insight into disrupted adipogenesis‑related pathways. The identified CpG methylation signature may serve as a basis for developing early molecular biomarkers and targeted strategies to improve EOPE diagnosis and management.

Keywords:  Classification; CpG; EOPE; Machine learning

DOI:  https://doi.org/10.1007/s43032-026-02183-8
J Cell Biol. 2026 Oct 05. pii: e202412222. [Epub ahead of print]225(10):

Spatially ordered zygotic genome activation fulfills embryo quality control.

Wenchao Qian, Hui Chen, Hongju Lee, Matthew C Good.

Early embryo development features autonomous, maternally driven cell divisions that self-organize the multicellular blastula or blastocyst tissue. Maternal control cedes to the zygote starting with the onset of widespread zygotic genome activation (ZGA), which is essential for subsequent cell fate determination and morphogenesis. Intriguingly, although ZGA onset is highly regulated at the level of the whole embryo, it can be non-homogenous and precisely patterned at the single-cell level. We previously demonstrated a stereotyped spatial and temporal ordering of ZGA in a model vertebrate embryo. Unknown, however, was whether this precise ZGA patterning was required for development. To address this fundamental question, we devised a strategy to spatially control cell divisions that perturb blastula embryo organization. We demonstrate the feasibility of spatially inverting the cell size pattern of embryos and find that these inverted embryos exhibit a flipped pattern of ZGA. Mispatterned ZGA along the animal-vegetal axis triggers embryo apoptosis, revealing that gastrula embryos have a built-in quality control system to sense inappropriate ZGA patterning, including regionalized defects in transcriptional onset. The quality control response is nonautonomous, dependent on an anti-apoptotic signal that suppresses cell death outside the animal hemisphere. These results reveal the requirement of properly patterned ZGA for normal development and the existence of a surveillance system of embryo quality control exquisitely tuned to the spatial and temporal ordering of genome activation and zygotic gene expression.

DOI: https://doi.org/10.1083/jcb.202412222
Growth Horm IGF Res. 2026 Sep 07. pii: S1096-6374(26)00044-4. [Epub ahead of print]85 101722

Fetal growth as an integrated maternal-placental-fetal system: What evidence can explain.

Gabriela Peña, Jaime Guevara-Aguirre, Alexandra Guevara, Antonio W D Gavilanes.

  Fetal growth results from the dynamic interaction of maternal, placental, and fetal factors. Most accounts converge on a simple but sophisticated mechanism: maternal status regulates substrate availability, the placenta transports nutrients, and the fetus adapts to a tightly controlled environment. This review tests that framework against two things it usually leaves out: how well current biomarkers and Doppler models perform, and what historical evidence of severe maternal starvation reveals about how much fetal size depends on maternal intake. The performance gap is consistent. Biomarker- and Doppler-based models for fetal growth restriction (FGR) detect over 85% of early-onset cases but only 66% or fewer of late-onset ones, a gap current angiogenic and Doppler markers cannot fully close. Placental insufficiency, not maternal diet alone, drives most pathological FGR: histological signs of maternal vascular underperfusion appear in roughly two-thirds of growth-restricted placentas, often missed by antenatal Doppler. During the Dutch Hunger Winter and the siege of Leningrad, months of severe caloric deprivation reduced birth weight by only a few hundred grams, yet still correlated with raised adult metabolic disease risk. Birth weight, in short, is a poor proxy for the intrauterine stress a fetus actually experiences. Two rare endocrine syndromes, Laron syndrome and Guevara-Rosenbloom syndrome, separate what insulin-like growth factor 1 (IGF-1) and insulin signaling each contribute to fetal size and later metabolic risk. These findings point toward assessment models that report detection and false-positive rates by gestational timing, and that account for metabolic programming even when birth weight does not drop.

Keywords:  Developmental programming; Fetal growth; Fetal growth restriction; Insulin-like growth factors; Placental biomarkers; Placental insufficiency

DOI:  https://doi.org/10.1016/j.ghir.2026.101722
Physiol Res. 2026 Aug 31. 75(4): 715-722

Altered Expression of Energy Metabolism-Related Genes in Placental Trophoblast Cells in Preeclampsia.

Jing Wang, Xin Wang, Ling-Chao Wang, Mei-Li Hu, Wei Liu, Jie Cui, Hong-Jie Li, Xian Zheng.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by new-onset hypertension after 20 weeks of gestation, with or without proteinuria, frequently accompanied by systemic arteriolar spasm and dysfunction or injury of multiple organs, including the liver, kidneys, and placenta. This study examined changes in glycolysis- and mitochondria-related gene expression in placental trophoblast cells in PE, aiming to elucidate the role of disrupted energy metabolism in its pathogenesis. A total of 86 pregnant women with singleton pregnancies who received routine prenatal care at the Affiliated Hospital of Hebei University between December 2023 and October 2024 and delivered via cesarean section were enrolled. Among them, 30 patients diagnosed with PE were included in the PE group, and 56 normotensive pregnant individuals were assigned to the control group. General clinical data were collected. The mRNA and protein expression levels of HK2, PKM2, silent information regulator two 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) in placental tissue were measured using real-time quantitative polymerase chain reaction and western blot (WB) analysis. There were no statistically significant differences in maternal age at delivery, body mass index, triglycerides, total cholesterol, or high-density lipoprotein cholesterol between groups (p > 0.5). Significant differences were observed in low-density lipoprotein cholesterol, neonatal birth weight, and 1-minute and 5-minute Apgar scores (p < 0.05). Expression levels of HK2, PKM2, and PGC-1alpha were significantly elevated in placental tissue from the PE group compared to the control group (p < 0.01), while SIRT1 expression was significantly reduced (p < 0.05). Placental tissue from patients with PE demonstrated upregulation of HK2, PKM2, and PGC-1alpha, and downregulation of SIRT1. Dysregulated expression of genes and proteins involved in energy metabolism may contribute to the pathogenesis of PE through impaired trophoblast function.
Environ Epidemiol. 2026 Oct;10(5): e526

Prenatal exposure to wildfire fine particulate matter and fetal growth outcomes in the United States: Findings from the ECHO Cohort.

Allison R Sherris, Logan C Dearborn, Dana E Goin, Christine T Loftus, Adam A Szpiro, Joan A Casey, Sindana D Ilango, Jyoti Angal, Deborah H Bennett, Miatta A Buxton, Carlos A Camargo, Kecia N Carroll, Marissa L Childs, Camille Cioffi, Lisa A Croen, Dana Dabelea, Stephanie M Eick, Shohreh F Farzan, Assiamira Ferrara, Erika Garcia, Alison Gemmill, Frank Gilliland, Rima Habre, Irva Hertz-Picciotto, Alison E Hipwell, Deborah Hirtz, Margaret R Karagas, Daphne Koinis-Mitchell, Amii M Kress, Leslie D Leve, Donghai Liang, Kristen Lyall, Lacey A McCormack, Cindy T McEvoy, Hooman Mirzakhani, Rachel Morello-Frosch, Zhongzheng Niu, Thomas G O'Connor, Alicia K Peterson, Rebecca J Schmidt, Catherine J Karr, Amy M Padula.

   Background: Increasing exposure to wildfire fine particulate matter (PM2.5) may pose unique risks to fetal development. We assessed associations between prenatal wildfire PM2.5 exposure and fetal growth outcomes, including birth weight at term, birth weight for gestational age z-scores, small for gestational age, and large for gestational age in the U.S. Environmental Influences on Child Health Outcomes Cohort.
Methods: The study included 20,034 births (2006-2020) from 30 cohort sites nationwide. We assigned daily wildfire PM2.5 at census-tract resolution and summarized average concentrations and the number of smoke days exceeding multiple intensity thresholds across pregnancy. We used covariate-adjusted mixed-effects models to estimate overall associations and distributed lag models and trimester-specific analyses to evaluate critical exposure windows across gestation, and we examined potential effect modification by US region, fetal sex, maternal race, and neighborhood poverty.
Results: Pregnancy wildfire exposure metrics, including mean prenatal PM2.5 and the number of smoke days, were not associated with study outcomes. Distributed lag and trimester-specific models did not show consistent sensitive windows of exposure associated with birth weight at term, birth weight for gestational age z-scores, or small for gestational age. A positive association was observed between higher early-pregnancy wildfire exposure and large for gestational age (odds ratio = 1.015 per smoke day, 95% confidence interval: 1.001, 1.029), though effect estimates were small in magnitude. No consistent effect modification was identified.
Conclusion: In this nationwide cohort, wildfire PM2.5 showed limited associations with fetal growth outcomes.

Keywords:  Air pollution; Birth weight; Birth weight for gestational age; Fetal growth; LGA; Pregnancy; SGA; Smoke; Wildfire

DOI:  https://doi.org/10.1097/EE9.0000000000000526
Clin Exp Reprod Med. 2026 Sep 09.

In vitro oocyte maturation is associated with altered OCT4 promoter methylation, DNMT expression, and early embryonic development in transgenic mouse embryos.

Nahid Pashaie, Delsuz Rezaee, Sara Hosseini, Mohammad Salehi.

   Objective: In vitro oocyte maturation (IVM) is widely used in assisted reproductive technologies; however, its potential effects on epigenetic regulation and embryonic development remain incompletely understood. In this study, we compared the developmental competence and epigenetic characteristics of transgenic mouse embryos derived from in vitro-matured and in vivo-matured oocytes.
Methods: A human OCT4-enhanced green fluorescent protein (EGFP) construct was microinjected into fertilized oocytes, and embryo development was evaluated by assessing cleavage and blastocyst formation rates. The methylation status of the OCT4 promoter was assessed using methylation-specific polymerase chain reaction (PCR), and the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b, and Dnmt3l) and endogenous Oct4 were analyzed using quantitative real-time PCR.
Results: Embryos derived from IVM oocytes exhibited significantly reduced cleavage and blastocyst formation rates compared with those derived from in vivo-matured oocytes. In addition, differences in OCT4 promoter methylation patterns and altered expression of DNMTs were observed between the two groups. In particular, increased Dnmt3a expression and decreased Oct4 expression were associated with embryos derived from IVM oocytes.
Conclusion: These findings suggest that IVM is associated with epigenetic alterations that may influence early embryonic development and the quality of transgenic embryos. Improved understanding of these effects may contribute to the optimization of IVM protocols and outcomes in assisted reproductive technologies.

Keywords:  DNA methylation; DNA methyltransferases; Embryo development; In vitro oocyte maturation; OCT4 promoter

DOI:  https://doi.org/10.5653/cerm.2026.09152