bims-placeb 2026-10-18 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2026–10–18
seventeen papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

Placental TRPV2 supports trophoblast function and normal fetal development.
Gene regulation at the early human maternal-fetal interface.
Understanding the involvement of HtrA4 during syncytiotrophoblast differentiation.
Sugar-Specific Modulation of Trophoblast Function and Bioenergetics Under Metabolic Stress Conditions.
The AMPK/mTOR axis is linked to placental ferroptosis in human gestational diabetes mellitus.
Directed conversion of porcine expanded pluripotent stem cells into trophoblast stem cells.
Placental Iron Homeostasis: Navigating the Delicate Balance Between Transport and Ferroptosis.
The Least Understood Placental Galectins: Galectin-14 and Galectin-16 in Human Pregnancy and Placental Biology.
Placental Insulin-like Growth Factor Signaling and Neurodevelopment: Emerging Evidence from the Placenta-Brain Axis.
Transcription-dependent polyadenylation signal activity contributes to transcriptomic regulation during Forskolin-induced BeWo cell syncytialization.
Beyond the Biomarkers: Gestation-Dependent Roles of sFLT-1 and PlGF in Human and Non-Human Mammalian Placental Development and Function.
Prenatal Cannabinoid Exposure Induces Sex-Specific Alterations in Fetal Growth and Placental Lipid Metabolism Gene Expression.
Early-Life exposure to environmental pollutants and endocrine disruptors: emerging risks and mechanistic insights in maternal, fetal, and child health.
Fetal-intrinsic antiviral mechanisms emerge over the course of gestation.
Elevated glucose levels trigger trophoblast cell invasion dysfunction through enhanced senescence and IGFBP4 signaling pathway.
Golgi disassembly: a key process for autophagy-mediated regulation of oocyte spindle migration.
Glucose transporter 8 and glycogenin-1 show distinct distributions in the conceptus and adjacent decidua of rats on gestational days 7 to 9.

Nat Commun. 2026 Sep 10. pii: 10673. [Epub ahead of print]17(1):

Placental TRPV2 supports trophoblast function and normal fetal development.

Katrien De Clercq, Vicente Pérez-García, Amitesh Panda, Seppe Gevaert, Jill Witvrouwen, Pilar Van Mechelen, Jorge Lopez-Tello, Katarzyna Maksym, Anna L David, Evy Van Den Broeck, Katrien Luyten, Andrei Segal, Suresh Poovathingal, Marta Wojno, Yuki Katanosaka, Rudi Vennekens, Vincent Pasque, Amanda N Sferruzzi-Perri, Thomas Voets, Joris Vriens.

While placental functioning arbitrates fetal outcome, the molecular players that underpin normal placental development remain poorly understood. Here, we provide evidence that the Transient Receptor Potential Vanilloid 2 (TRPV2) channel plays an important role in normal placental development, determining fetal size and survival. Its absence severely affects placental morphology, causing fetal growth restriction and embryonic lethality, which was found to be allocated to a non-redundant role in the trophoblast, but not in the embryo. CRISPR/Cas9-mediated Trpv2 deletion in mouse trophoblast stem cells demonstrated that Trpv2 contributes to the differentiation towards Syncytiotrophoblast layer II (SynTII) cells, which was confirmed by the growth restriction phenotype in SynTII-specific Trpv2 knockout animals. Finally, TRPV2 was functionally expressed in human trophoblast cells and enriched in trophoblast populations undergoing syncytial differentiation. Together, our findings identify an important role for TRPV2 during placental development and consequently fetal outcomes.

DOI: https://doi.org/10.1038/s41467-026-77576-z
Nat Rev Genet. 2026 Oct 12.

Gene regulation at the early human maternal-fetal interface.

Ana Paredes, Christina E Kim, Roser Vento-Tormo.

Pregnancy is a distinct physiological context in which the mother hosts and nurtures the development of a genetically distinct fetus. Healthy pregnancy outcomes rely on successful placental development, during which specialized placental cells with fetal genotype, known as trophoblasts, drive the establishment of the maternal-fetal interface, a balanced tissue ecosystem that supports fetal development while safeguarding maternal well-being. Advances in single-cell, single-nuclei and spatial genomics technologies, along with data science, are now providing an unprecedented view of trophoblast regulation, which drives their differentiation into diverse cell subtypes that dynamically transform the maternal niche. More specifically, these cells modulate the immune system and remodel the vasculature to facilitate communication with maternal cells, leading to the successful formation of the maternal-fetal interface. These advances, when combined with in vitro modelling, hold promise for inferring causality in mechanisms that govern genome regulation, cellular behaviour and ultimately pregnancy homeostasis and maladaptive responses.

DOI: https://doi.org/10.1038/s41576-026-01014-5
Front Cell Dev Biol. 2026 ;14 1926149

Understanding the involvement of HtrA4 during syncytiotrophoblast differentiation.

Bothidah Thach, Yao Wang, Chaitali Dekiwadia, Guiying Nie.

  The syncytiotrophoblast (STB), the outermost layer of the human placenta, is vital to pregnancy health as it functions as the direct maternal-fetal interface. Being terminally differentiated and multinucleated, STB cannot divide but is formed/sustained by fusion of cytotrophoblasts throughout pregnancy. HtrA4, produced only in placentas of humans and high-order primates, is obligatory for syncytialization, including differentiation of trophoblast stem cells (TSCs) into STB as HtrA4 knockdown (KD) blocks the process; however, how HtrA4 mediates the process remains unknown. The current study aimed to understand how HtrA4 is involved in STB differentiation, by analyzing HtrA4-KD TSCs using mRNA transcriptomics and scanning electron microscopy (SEM). We first investigated how control and HtrA4-KD TSCs, respectively, altered protein-coding gene expressions globally upon stimulation for STB differentiation, then compared the significantly differentially expressed genes (DEGs) to identify the deficiencies of HtrA4-KD cells. Among the DEGs associated with STB differentiation of controls, 25% of them also occurred in HtrA4-KD cells, implying these were HtrA4-independent; in contrast, the remaining 75% DEGs were severely attenuated or completely blocked in HtrA4-KD cells, signifying these were HtrA4-modulated or HtrA4-dependent. Analysis of biological processes, molecular functions, and cellular pathways associated with these distinctive DEGs suggested that early STB differentiation events, such as ceasing cell division and initiating autophagy, were un-influenced by HtrA4. However, many subsequent processes of STB differentiation were partially or fully influenced by HtrA4, some of which included hormone activity, cell surface and extracellular matrix remodeling, adjustments in cell-cell signaling, and restructuring of various components of the cytoplasm/cytoskeleton. Moreover, our data suggested that pathways related to nervous system development were suppressed during STB differentiation, and this was influenced by HtrA4. Furthermore, it was indicated that altering protein binding was a major juncture of HtrA4 influence, and mitigating oxidative stress during STB differentiation might be tightly coupled with HtrA4. By SEM examination of the morphological changes along the time course of STB differentiation, we further visually demonstrated that HtrA4-KD cells commenced the differentiation process, but were blocked from progressing into multinucleated STB. Collectively, these findings provide important new insights into the pivotal role of HtrA4 in STB differentiation.

Keywords:  HtrA4; cell fusion; placenta; syncytialization; syncytiotrophoblast; trophoblast; trophoblast differentiation; trophoblast stem cells (TSCs)

DOI:  https://doi.org/10.3389/fcell.2026.1926149
Int J Mol Sci. 2026 Oct 08. pii: 8920. [Epub ahead of print]27(19):

Sugar-Specific Modulation of Trophoblast Function and Bioenergetics Under Metabolic Stress Conditions.

Elizabeth Thurmond, Madeline Boyer, Benjamin T Bikman, Paul R Reynolds, Juan A Arroyo.

  How sugars other than glucose affect trophoblast function is poorly understood, particularly under the metabolic stress of diabetic pregnancy. We compared glucose, fructose, and the minimally metabolized sugar allulose in two trophoblast cell lines, SW71 (first-trimester, extravillous-like) and BeWo (choriocarcinoma-derived, villous). Each sugar was added at 25 mM for 24 h to the cells' standard glucose-containing media (11 mM, SW71; 17.5 mM, BeWo) to model metabolic stress. All three sugars increased the number of cells recovered (2.4- to 6.5-fold in SW71; ~10- to 15-fold in BeWo) and reduced viability (~9-75%), with fructose causing the largest loss in both lines. Intracellular reactive oxygen species increased 5.2- to 7.8-fold with all sugars. Oxygen consumption differed by sugar: in SW71 cells, glucose and allulose increased ADP-stimulated and succinate-supported respiration, whereas fructose reduced it, and in BeWo cells only fructose increased it. SW71 invasion was ~7-fold higher after allulose than after glucose or fructose. BeWo cells were studied undifferentiated, so effects on syncytialization were not assessed. The three sugars are therefore not interchangeable in their effects on trophoblast cells in vitro. Because the concentrations exceed those in maternal blood, these findings are hypothesis-generating and require testing at physiological concentrations and in primary trophoblast models.

Keywords:  gestational diabetes; oxidative stress; placental metabolism; sugar alternatives; trophoblast function

DOI:  https://doi.org/10.3390/ijms27198920
Placenta. 2026 Oct 12. pii: S0143-4004(26)00720-4. [Epub ahead of print]186 148-159

The AMPK/mTOR axis is linked to placental ferroptosis in human gestational diabetes mellitus.

Qian Li, Xiaoyi Yin, Ziyi Guo, Haobin Zhao, Niannian Li, Yuchun Zhu, Guanglei Wang.

   BACKGROUND: Ferroptosis has been closely implicated in placenta-related complications. Nevertheless, its specific role in the placenta of gestational diabetes mellitus (GDM) remains poorly understood. We hypothesized that ferroptosis contributes to impaired placental cell function in GDM and that the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) axis acts as an potential regulator of ferroptosis.
METHODS: Term placental tissues from pregnant women with GDM and healthy controls were analyzed, and the human chorionic trophoblast line (HTR8/SVneo) was used in the in vitro experiments.
RESULTS: Altered levels of ferroptosis markers-transferrin receptor 1 (TfR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), ferrous iron and malondialdehyde (MDA), and potential ferroptosis mediators-reactive oxygen species (ROS), AMPK, and mTOR were observed in GDM placentas compared to control. AMPK inhibitor, AMPK activator, and mTOR inhibitor were applied to modulate the AMPK/mTOR signaling axis in in vitro experiments. Our in vitro data revealed that modulation of AMPK or mTOR activation directly affects the induction of ferroptosis as well as trophoblast cell proliferation and migration.
CONCLUSIONS: Our study suggests that AMPK/mTOR axis is closely associated with placental ferroptosis which may represent a promising therapeutic target for mitigating GDM-related placental complications following further validation in animal models.

Keywords:  AMPK; Ferroptosis; GDM; Oxidative stress; Placenta; mTOR

DOI:  https://doi.org/10.1016/j.placenta.2026.10.003
Biol Reprod. 2026 Oct 16. pii: ioag234. [Epub ahead of print]

Directed conversion of porcine expanded pluripotent stem cells into trophoblast stem cells.

Chi-Hun Park, Young-Hee Jeoung, JiTao Wang, Bhanu P Telugu.

  Trophoblast stem cells (TSCs) serve as a valuable system for investigating the signaling pathways that regulate extraembryonic lineage commitment. Although trophoblast specification has been extensively characterized in humans and rodents, comparable tools and molecular frameworks remain underdeveloped in pigs, a species of significant agricultural and biomedical relevance. This study identifies defined biochemical conditions that enable efficient conversion of porcine (p) expanded pluripotent stem cells (EPSCs) into induced TSCs (iTSCs). The results demonstrate that combined inhibition of TGF-β/Activin and MEK/ERK signaling is sufficient to induce and maintain core trophoblast regulators, including CDX2, GATA3, KRT7/18, HAND1, and ELF5, while suppressing pluripotency networks. Transcriptomic analyses, benchmarked against porcine in vivo trophoblast reference datasets, indicate that piTSCs closely resemble peri-implantation and term trophoblast populations, confirming successful lineage conversion from the pluripotent state. In vivo, piTSCs formed only small, lineage-restricted lesions lacking ectodermal and endodermal derivatives and exhibiting widespread immunoreactivity for trophoblast markers. In contrast, parental pEPSCs generated teratomas containing derivatives of all three germ layers. Collectively, these findings establish a robust experimental framework for trophoblast induction and characterization in pigs, providing a model to investigate conserved and species-specific mechanisms of trophoblast development and placental biology.

Keywords:  Pig; extraembryonic development; lineage conversion; pluripotent stem cells; trophoblast stem cells

DOI:  https://doi.org/10.1093/biolre/ioag234
Int J Mol Sci. 2026 Oct 04. pii: 8856. [Epub ahead of print]27(19):

Placental Iron Homeostasis: Navigating the Delicate Balance Between Transport and Ferroptosis.

Dariusz Szukiewicz.

  As an essential micronutrient, iron plays a vital role in oxygen transport, deoxyribonucleic acid synthesis, and energy production and is a redox-active cofactor for many biological processes. However, ferrous iron (Fe2+) is toxic to cells because it reacts with hydrogen peroxide in the Fenton reaction to generate the hydroxyl (free) radical, a key player in oxidative stress, leading to lipid peroxidation and iron-dependent cell death (ferroptosis). Therefore, iron homeostasis is precisely regulated. Maintaining appropriate iron metabolism during pregnancy is a major challenge, as it requires adaptation at the level of the utero-placental-fetal unit to the dynamic changes in the demand for iron in the developing fetus during the later weeks of pregnancy. The distinction between physiological (normal) anemia, which results from hemodilution and leads to the depletion of intracellular iron stores (ferritin) in placental cells, and the manifestation of the toxic effects of iron overload and/or oxidative stress is not always clear. Moreover, chronic inflammation during pregnancy associated with increasingly common metabolic disorders such as obesity, diabetes and hypertension may induce ferroptosis. This review presents the current understanding of placental iron homeostasis and its disturbances, focusing on the role of ferroptosis in placental dysfunction. The rationale for potentially effective anti-ferroptotic treatment is also presented.

Keywords:  Fenton reaction; ferroptosis; human placenta; human pregnancy; iron metabolism; iron overload; lipid peroxidation; placental dysfunction; trophoblast ferroptosis

DOI:  https://doi.org/10.3390/ijms27198856
Diagnostics (Basel). 2026 Sep 30. pii: 3188. [Epub ahead of print]16(19):

The Least Understood Placental Galectins: Galectin-14 and Galectin-16 in Human Pregnancy and Placental Biology.

Zoltan Kozinszky, Yakov Rachamin Karo, Jakó Mária, Márió Vincze, János Sikovanyecz, János Sikovanyecz, Zsolt Tidrenczel, Bálint Koppány, Giuseppe Gullo, László Kaiser, Eszter Ducza, Szabolcs Várbíró, Andrea Surányi.

  Galectins represent a family of proteins which are capable of specifically binding to beta-galactoside-containing sugar molecules, known as glycans. Galectins possess carbohydrate recognition domains (CRDs) that fundamentally determine their ability to bind to sugars. Galectin-14 (Gal-14) and galectin-16 (Gal-16) are members of the galectin family that is particularly associated with the placenta. The galectins in the placenta constitute a specialized subgroup functioning at the maternal-fetal interface. They are expressed primarily in the syncytiotrophoblasts. This trophoblast layer is in direct contact with maternal blood and plays a crucial role in the metabolic, hormonal and immunological interactions between the fetus and the pregnant woman. In order to prepare this structured narrative review, we conducted a structured literature search across the MEDLINE (PubMed), Embase, Cochrane Library and Web of Science Core Collection databases; the final search has been performed on 1 July 2026. The search strategy has combined the terms galectin-14/LGALS14 and galectin-16/LGALS16 with terms related to the placenta, trophoblast, pregnancy, placentation and pregnancy complications. Search results were imported into Mendeley Reference Manager to remove duplicates, and the reference lists of relevant review articles and studies were manually screened. Two reviewers (Z.K. and A.S.) independently screened the titles and abstracts and subsequently evaluated the potentially relevant full-text articles. The final evidence synthesis included primary studies that directly investigated the expression, function, regulation, or clinical associations of LGALS14 or LGALS16; secondary publications were used for background and contextual information. In experimental studies, galectin-14 has been linked to trophoblast migration and invasion-involving mechanisms such as the PI3K/Akt signaling pathway, MMP-9 and N-cadherin-as well as to the modulation of activated maternal immune cell function. Galectin-16 is structurally more distinct and exhibits reduced classical β-galactoside-binding capacity; it appears to be closely associated with trophoblast differentiation and syncytialization, presumably through intracellular protein interactions. Altered expression of placenta-specific galectins has been observed in preeclampsia and fetal growth restriction; however, the causal relationship remains unclear. Clinical evidence regarding their use as biomarkers is emerging at this time; therefore, neither galectin-14 nor galectin-16 can be currently considered as a validated, clinically applicable biomarker. Altogether, available evidence mandates further study of galectin-14 and galectin-16, as they may be important regulators of placental biology and potential biomarker candidates. However, their physiological functions and clinical utility have not yet been sufficiently confirmed; therefore, further prospective and functional studies are required. The strongest putative mechanistic link to the development of preeclampsia exists for galectin-14, primarily involving trophoblast migration and invasion as well as PI3K/Akt-related signaling pathways. In contrast, evidence in connection with the direct role of galectin-16 is limited at present.

Keywords:  LGALS14; LGALS16; galectin-14; galectin-16; maternal–fetal interface; placenta; pregnancy complications; trophoblast

DOI:  https://doi.org/10.3390/diagnostics16193188
Cells. 2026 Sep 27. pii: 1759. [Epub ahead of print]15(19):

Placental Insulin-like Growth Factor Signaling and Neurodevelopment: Emerging Evidence from the Placenta-Brain Axis.

Annemarie J Carver, Eleanor G Williamson, Hanna E Stevens.

  The field of neuroplacentology is a growing area that focuses on the influence of placental function on brain development. This field has expanded our understanding of the placenta's crucial role in proper neurodevelopment as well as placental anomalies that increase the risk of adverse neurodevelopmental outcomes. Neuroplacentology studies have revealed distinct roles of placentally provided hormones and nutrients in neurodevelopment whose disruption by perinatal problems, including inflammation, can increase the risk of neurodevelopmental disorders such as autism spectrum disorder and ADHD. Placental insulin-like growth factor signaling significantly influences brain growth in animal model studies and is tightly linked with human neurodevelopmental outcomes. Insulin-like growth factor signaling is well-established as a regulator of placental function and is fundamental in fetal brain cell developmental processes and plays a role in inflammation. Placental insulin-like growth factor signaling underlies the placental production and delivery of hormones and nutrients that are necessary for fetal neural cell proliferation, differentiation, and growth. It is especially important to study this pathway in the placenta due to aberrant insulin-like growth factor signaling found in conditions such as preterm birth, fetal growth restriction, gestational diabetes, and obesity. All these conditions are linked to a greater risk for neurodevelopmental disorders, neuroinflammation, and other anomalies. This research subfield has also revealed sex differences in the insulin-like growth factor signaling pathway that will contribute to understanding the etiologies of these conditions. This area of study has and will continue to identify specific mechanisms, many currently in model systems, which could eventually be leveraged in preventative and interventive care to improve neurodevelopmental outcomes.

Keywords:  IGF signaling; inflammation; insulin-like growth factors; neurodevelopment; neuroplacentology; placenta; placenta–brain-axis

DOI:  https://doi.org/10.3390/cells15191759
Front Cell Dev Biol. 2026 ;14 1958080

Transcription-dependent polyadenylation signal activity contributes to transcriptomic regulation during Forskolin-induced BeWo cell syncytialization.

Juan Liu, Guolin Ye, Xin Liu, Haiming Jing, Shan Gao, Zhongyuan Deng, Junyu Ning.

  Polyadenylation, a core transcriptional step governed by polyadenylation signals (PAS), functionally interacts with transcription. Nevertheless, how PAS sequences respond to variable transcriptional output remains poorly characterized. Here, we precisely modulated cellular transcription levels by integrating SV40 promoter truncation with a Tet-On dual-luciferase reporter system. Diminished polyadenylation efficiency accompanies lowered promoter activity, and graded transcription assays revealed a tiered PAS processing model: canonical and suboptimal PASs maintain stable 3'-end processing at high transcription levels, whereas non-canonical PASs display compromised processing efficiency with rising transcription. During forskolin(FSK)-induced BeWo cell syncytialization, endogenous trophoblast fusion genes carrying potent canonical PASs were selectively mobilized upon transcriptional activation to enrich differentiation transcripts and sustain orderly syncytiotrophoblast maturation. Together, these findings reveal a hierarchical transcription-polyadenylation axis that associate with placental trophoblast syncytialization. They fill key gaps in mRNA processing and provide a foundation for studying the transcriptional regulatory mechanisms underlying trophoblast differentiation.

Keywords:  placenta; polyadenylation; polyadenylation signals; transcriptional activity; trophoblast syncytialization

DOI:  https://doi.org/10.3389/fcell.2026.1958080
Cells. 2026 Oct 06. pii: 1817. [Epub ahead of print]15(19):

Beyond the Biomarkers: Gestation-Dependent Roles of sFLT-1 and PlGF in Human and Non-Human Mammalian Placental Development and Function.

Zoe Byrne, Sonja Brennan, David Watson, Donna Rudd, Yoga Kandasamy.

  Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) are established biomarkers of placental dysfunction, but their functions extend beyond the maternal circulating ratio. This structured narrative review examines the FLT1-PlGF-vascular endothelial growth factor system across implantation, trophoblast differentiation, uterine vascular transformation, foetoplacental angiogenesis, exchange capacity development and late-gestational maturation. Human evidence is integrated with selected non-human mammalian studies according to gestational stage, cellular source, anatomical compartment, molecular isoform and placental architecture. We use a compartmentalised angiogenic rheostat as a qualitative organising framework, not an experimentally validated model. It integrates established ligand-receptor biology with human observations and experimental perturbations: PlGF modifies FLT1 signalling and VEGF-A availability, whereas membrane and soluble FLT1 influence ligand distribution and vascular responses. Experimental evidence supports physiological ligand restraint and the pathogenic effects of excessive sFLT-1; human associations do not invariably establish the initiating placental lesion. Pre-eclampsia, foetal growth restriction and invasive placentation illustrate distinct contexts in which angiogenic regulation may become maladaptive. The maternal sFLT-1/PlGF ratio is therefore interpreted as a circulating indicator of placental vascular stress rather than a direct measurement of local signalling.

Keywords:  PlGF; VEGF; angiogenesis; fetal growth restriction; placenta; placental growth factor; pre-eclampsia; sFLT-1; soluble fms-like tyrosine kinase-1; trophoblast

DOI:  https://doi.org/10.3390/cells15191817
Cannabis Cannabinoid Res. 2026 Oct 12. 25785125261497796

Prenatal Cannabinoid Exposure Induces Sex-Specific Alterations in Fetal Growth and Placental Lipid Metabolism Gene Expression.

Rachel West, Adrian Courville, Cristine Camp, Paige Drotos, Carly Parker, Miranda Reed.

   BACKGROUND: Prenatal cannabis use is becoming increasingly more commonplace. However, cannabis exposure is linked to adverse pregnancy outcomes, including gestational hypertension, preeclampsia, and preterm birth. The aim of this study was to determine the morphological and molecular effects of prenatal cannabinoid exposure on the placenta.
METHODS: Pregnant Sprague-Dawley rats were exposed daily to vaporized THC (100 mg/mL) starting at gestational day (GD)5 until GD19, when dams were sacrificed and fetuses and placentas collected. Fetuses were genotyped for genetic sex, and transcriptomic analysis was performed on male and female THC-exposed and control placentas.
RESULTS: On GD19, only the female fetuses from the THC group were significantly larger than those of the control, with no significant differences in placental weights or fetal:placental weight ratios. RNA sequencing revealed enriched biological processes related to nutrient transport and lipid catabolism, protein-lipid complex formation, and lipoprotein particle remodeling and organization. Further transcriptomic analysis determined that the differentially expressed genes and enriched biological processes related to lipid metabolism were preferentially enriched in the female THC placentas compared to the male, suggesting a sex-specific effect.
DISCUSSION: Collectively, these data present sex-specific effects of prenatal cannabinoid exposure on placental growth and global gene expression. These data also suggest that sex influences gene expression of genes related to lipid metabolism in the THC-exposed placentas.

Keywords:  cannabis; metabolism; placenta; pregnancy

DOI:  https://doi.org/10.1177/25785125261497796
Environ Res. 2026 Oct 13. pii: S0013-9351(26)02210-3. [Epub ahead of print] 125878

Early-Life exposure to environmental pollutants and endocrine disruptors: emerging risks and mechanistic insights in maternal, fetal, and child health.

B Nishanthini, A Yazhini, Pramilaa Kumar, Panchamoorthy Saravanan, R Rajeshkannan, M Rajasimman, S Venkat Kumar.

  Exposure to environmental pollutants and endocrine-disrupting chemicals (EDCs) in early life is a critical public health issue because it can alter developmental programming that impacts susceptibility to disease throughout life. The prenatal and early postnatal periods are times of vulnerability when exposure to environmental stressors may impact endocrine signalling, placental function, epigenetic regulation, and metabolic homeostasis. There is increasing evidence that exposure to bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), pesticides, heavy metals, and air pollutants has been associated with pregnancy outcomes, neurodevelopmental disorders, metabolic dysfunction, endocrine abnormalities and reproductive impairments. Exposomics, high-resolution mass spectrometry, biomonitoring, and passive sampling technologies have made crucial advances in characterising complex environmental exposures. At the same time, novel methods such as multi-omics, single-cell sequencing, spatial biology and microbiome studies have yielded more detailed mechanistic understanding of how environmental factors can impact developmental processes via epigenetic, inflammatory, oxidative stress, and endocrine pathways. The placenta has emerged as a valuable biomarker matrix for assessing fetal exposure and developmental programming. Exposure routes, biomonitoring methods, placental processes, molecular and epigenetic modifications, and the impacts of early-life environmental exposures on neurodevelopment, metabolism, endocrine function, and reproduction are all summarised in this review. It also emphasises current advancements in exposure assessment, preventive measures, and policy frameworks, highlighting the importance of life-course perspectives and environmental justice. To identify important windows of susceptibility, improve risk assessment, and develop strategies to safeguard maternal and child health, exposomics in conjunction with systems biology and longitudinal epidemiological approaches will be essential.

Keywords:  Biomonitoring; Early-life exposure; Endocrine-disrupting chemicals; Environmental health; Metabolic programming; Neurodevelopment

DOI:  https://doi.org/10.1016/j.envres.2026.125878
bioRxiv. 2026 Sep 28. pii: 2026.09.22.753282. [Epub ahead of print]

Fetal-intrinsic antiviral mechanisms emerge over the course of gestation.

Drake T Philip, Madeline S Merlino, Elizabeth A Kennedy, Kristen Walsh, Elizabeth Ramos, Gretchen S Fazakerly, Christopher A Hunter, Kellie A Jurado.

Congenital viral infections have variable effects on pregnancy outcomes with implications for maternal and fetal health. However, the maternal and fetal immune mechanisms that emerge over the course of gestation to determine protective or pathological outcomes remain poorly understood. Here, we use the emerging congenital pathogen Oropouche virus (OROV) to examine gestational stage-dependent differences in maternal and fetal outcomes in a mouse model of congenital infection. Pregnant mice (dams) infected during early gestation resist severe OROV disease, whereas mid-gestation-infected dams succumb to infection. In contrast, fetal pathology is substantial following early gestation infection but limited following infection during mid-gestation, revealing discordant maternal and fetal susceptibility across gestation. Mid-gestation fetal tissues effectively restricted vertical transmission compared to early gestation fetal tissues, corresponding with reduced fetal pathology. Moreover, both placental and fetal tissue cleared OROV RNA over the course of infection, independent of gestational stage, and failure to clear viral RNA was associated with severe fetal pathology. Spatial analysis of early gestation implantation sites further revealed distinct regional susceptibility to OROV infection across the maternal-fetal interface. We identified potential instances of placental-independent vertical transmission via direct fetal contact with highly infected regions of the contralateral maternal uterus. Finally, we uncovered an unexpected mechanism by which type I interferon signaling contributes to inter-fetal immune crosstalk to restrict both OROV vertical transmission and pathology. Together, these findings establish the fetus as an active participant in antiviral defense and reveal previously unrecognized mechanisms by which fetal-intrinsic antiviral immune responses limit congenital viral infection and disease.

DOI: https://doi.org/10.64898/2026.09.22.753282
J Reprod Immunol. 2026 Oct 02. pii: S0165-0378(26)00142-7. [Epub ahead of print]178 104973

Elevated glucose levels trigger trophoblast cell invasion dysfunction through enhanced senescence and IGFBP4 signaling pathway.

Xiaolu Zhang, Mingqing Li, Songping Liu.

  Gestational diabetes mellitus (GDM) is related to multiple negative pregnancy outcomes such as miscarriage, pre-eclampsia and so on. Cell senescence was considered potential mechanism of GDM. However, the role and mechanism of high glucose and cellular senescence in trophoblast cells are largely unknown. Here, we observed cell senescence and expression of glucose transporter 3 (GLUT3) were up-regulated in GDM placenta. In vitro study confirmed the migration and invasion abilities were impaired in H2O2-induced senescent choriocarcinoma JEG3 cells. Additionally, high glucose triggered senescent phenotype, impaired migration and invasion of senescent JEG3 cells. The expression of GLUT3 was increased in senescent JEG3 cells, and overexpression of GLUT3 induced cell senescence, suggesting a feedback loop between cell senescence and up-regulation of GLUT3. Overexpression of GLUT3 enhanced glucose uptake and lactate accumulation, and decreased migration and invasion of JEG3 cells, mechanically, these processes were dependent on IGFBP4. These data suggest that GLUT3/high glucose induces migration and invasion dysfunction of trophoblast cells, possibly contributing to placental dysfunction of GDM.

Keywords:  GLUT3; Gestational diabetes mellitus; IGFBP4; Senescence; Trophoblast cell

DOI:  https://doi.org/10.1016/j.jri.2026.104973
Autophagy. 2026 Oct 11.

Golgi disassembly: a key process for autophagy-mediated regulation of oocyte spindle migration.

Jiaqi Zhang, Nan Wang, Xiaomeng Wang, Jie Qiao, Peng Yuan, Liying Yan.

  Although the Golgi apparatus undergoes extensive disassembly during mitosis to ensure its equitable partitioning into two daughter cells, the extreme asymmetry of oocyte meiosis obviates this need, raising fundamental questions about the existence and necessity of Golgi disassembly in oocytes. Herein, we demonstrated the existence of a Golgi disassembly process during oocyte meiosis I, which peaked at germinal vesicle breakdown (GVBD) and was largely completed by metaphase II (MII). Strikingly, the vesiculation stage of Golgi disassembly exhibited a function divergent from mitosis by governing spindle cortical migration during metaphase I (MI), thereby ensuring oocyte polarity establishment. Moreover, we found that macroautophagy/autophagy negatively regulated the vesiculation stage of Golgi disassembly: its hyperactivation suppressed vesiculation, whereas its inhibition conversely accelerated this process. Mechanistically, MIA2 and SFT2D2 were identified as key downstream effectors through which autophagy controlled Golgi vesiculation. MIA2 mediated autophagy-dependent regulation of Golgi dynamics through its two LIR motifs, thereby linking autophagic signaling to Golgi remodeling. Specifically, autophagy activation downregulated MIA2, thus inhibiting the ubiquitin-dependent degradation of SFT2D2, consequently suppressing Golgi vesiculation and spindle migration during oocyte meiosis I; conversely, autophagy inhibition accelerated these processes by increasing MIA2 to promote SFT2D2 degradation. These findings elucidate the key role of autophagy in regulating Golgi disassembly, thereby providing a new organelle-based perspective on how autophagy contributes to oocyte spindle migration. Furthermore, our work identifies a novel Golgi-dependent mechanism for oocyte polarity establishment and uncovers the divergent functions of Golgi remodeling across distinct division modes.

Keywords:  Autophagy; MIA2; SFT2D2; golgi disassembly; meiosis; oocyte; spindle migration

DOI:  https://doi.org/10.1080/15548627.2026.2747860
Am J Vet Res. 2026 Oct 15. 1-7

Glucose transporter 8 and glycogenin-1 show distinct distributions in the conceptus and adjacent decidua of rats on gestational days 7 to 9.

Pelin Coştur Filiz, Emin Türkay Korgun.

   Objective: To describe the spatial and gestational stage-associated distribution of glucose transporter 8 (GLUT8) and glycogenin-1 (GN1) immunoreactivity in rat implantation sites during early gestation.
Methods: This descriptive archival immunohistochemical study examined paraffin-embedded implantation site material collected in 2001. Glucose transporter 8 and GN1 were immunolabeled on separate serial sections using biotin-streptavidin-peroxidase detection with 3-amino-9-ethylcarbazole as chromogen. Sections were evaluated independently by 2 observers with respect to anatomical distribution and cellular localization.
Results: Implantation site material from 32 pregnant Wistar rats was examined (gestational day [GD]-7, n = 10; GD8, 11; GD9, 11). Glucose transporter 8 immunoreactivity was detected at GD7 in the parietal and visceral endoderm and extraembryonic ectoderm and at GD8 additionally in the decidua. No specific GN1 immunoreactivity above background was detected in the decidua examined at GD7; GN1 was detected at GD8 in the extraembryonic compartment and the decidua, with weak immunoreactivity in adjacent myometrial smooth muscle cells. At GD9, both proteins were evident in trophoblast giant cells.
Conclusions: GLUT8 and GN1 showed distinct spatial and stage-associated patterns of immunoreactivity during early rat implantation. Because the 2 proteins were labeled on separate serial sections and the compartments available for assessment differed between markers at GD7, comparisons should be restricted to anatomical compartment-level distribution and do not establish cellular colocalization or functional interaction.
Clinical Relevance: These descriptive data provide baseline information on glucose- and glycogen-related protein distribution during early implantation and may inform future comparative studies of early placental development in veterinary species.

Keywords:  GLUT8; glycogenin-1; immunohistochemistry; implantation site; rat

DOI:  https://doi.org/10.2460/ajvr.26.08.0355