bims-placeb 2026-03-08 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2026–03–08
seven papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

Conserved gene expression patterns in the placenta underlie pregnancy complications associated with hypoxia in mice and humans.
Bisphenol A induces IRE1-dominant endoplasmic reticulum stress, apoptosis, and functional impairment in BeWo trophoblast cells.
Ex vivo human placental imaging: Navigating modalities, scales, and analysis approaches to obtain fit-for-purpose data.
ZFP36 inhibits trophoblast ferroptosis and attenuates preeclampsia development by promoting NCOA4 mRNA degradation and suppressing ferritinophagy.
Proteomic Epithelial-To-Mesenchymal Transition Signature in Fetoplacental Small Extracellular Vesicles of Early-Onset Preeclampsia.
Kisspeptin Restores Placental mTOR Signaling and Improves Glucose Homeostasis Mediators Disrupted by Maternal Hypothyroidism in Rats.
Deficient extravillous trophoblast invasion caused by impaired sialylation-Siglec-7 interaction contributes to recurrent pregnancy loss.

Cell Mol Life Sci. 2026 Mar 04.

Conserved gene expression patterns in the placenta underlie pregnancy complications associated with hypoxia in mice and humans.

Emma J Siragher, Josephine S Higgins, Owen R Vaughan, Abigail L Fowden, Amanda N Sferruzzi-Perri.



Keywords:  Growth restriction; Hypoxia; Mouse models; Placenta; Pregnancy

DOI:  https://doi.org/10.1007/s00018-026-06110-7
Reprod Toxicol. 2026 Feb 26. pii: S0890-6238(26)00051-1. [Epub ahead of print] 109208

Bisphenol A induces IRE1-dominant endoplasmic reticulum stress, apoptosis, and functional impairment in BeWo trophoblast cells.

Fatma Beyza Sag, Zehra Sezer, Elif Guzel.

  Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in polycarbonate plastics and epoxy resins, resulting in human exposure primarily through food-contact materials and thermal paper, as well as environmental sources. Studies suggest that BPA has adverse effects on trophoblast cells, which are critical for placental formation, and that the endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may contribute to BPA-induced cellular dysfunction. However, the mechanisms by which BPA affects placental trophoblast function remain incompletely understood. This study aimed to explore the connection between ER stress/UPR signaling and BPA-induced trophoblast disfunction. BeWo cells were stimulated with forskolin to induce a syncytium formation, a hallmark of trophoblast differentiation, and then exposed to different concentrations of BPA. The effect of BPA on differentiation and secretion capacity, viability, and apoptosis of the trophoblast cells was examined comparing the results with data related to ER stress. Our findings provide evidence that ER stress/UPR activation is involved in BPA-induced trophoblast dysfunction and that BPA-induced apoptosis may be linked to ER stress. In conclusion, this study offers mechanistic insights into how BPA impacts trophoblast cells and may help in understanding the pregnancy-related adverse outcomes associated with BPA exposure.

Keywords:  apoptosis; bisphenol A; endoplasmic reticulum stress; placenta; trophoblast cells; trophoblast differentiation; unfolded protein response

DOI:  https://doi.org/10.1016/j.reprotox.2026.109208
Placenta. 2026 Mar 02. pii: S0143-4004(26)00072-X. [Epub ahead of print]

Ex vivo human placental imaging: Navigating modalities, scales, and analysis approaches to obtain fit-for-purpose data.

Mary E Spring, Alys R Clark, Gowsihan Poologasundarampillai, Michele C Darrow, Joanna L James.

  The placenta is one of the most accessible human organs for ex vivo imaging, yet it still remains one of the least understood. Recent advances in ex vivo imaging approaches provide opportunities to capture the complex anatomy of the placenta and its vasculature across multiple scales. However, alongside this it is imperative to consider how we can optimise workflows - from tissue sampling and preparation to analysis - to obtain meaningful quantitative data from imaging, including computational handling of large and complex datasets at scale. Indeed, such tools are critical to advance our insight into how structure-function relationships change across gestation, or in pregnancy pathologies. This review first provides a quantitative overview of placental structure, then critically considers the advantages and disadvantages of current and emerging ex vivo placental imaging approaches from the subcellular level to the organ scale, with a focus on methods and considerations to enable meaningful quantification and downstream use of data.

Keywords:  Confocal; Electron microscopy; Optical coherence tomography; Placenta; Synchrotron; microCT

DOI:  https://doi.org/10.1016/j.placenta.2026.03.001
Biochem Pharmacol. 2026 Feb 27. pii: S0006-2952(26)00167-X. [Epub ahead of print]248 117836

ZFP36 inhibits trophoblast ferroptosis and attenuates preeclampsia development by promoting NCOA4 mRNA degradation and suppressing ferritinophagy.

Man Gao, Xue Yang, Xiuxia Wang, Tong Liu.

  Preeclampsia (PE), a pregnancy-specific disorder characterized by placental dysfunction and severe maternal-fetal complications, involves ferroptosis-an iron-dependent cell death driven by oxidative stress and lipid peroxidation. This study investigated the role of zinc-finger protein 36 (ZFP36) in regulating ferroptosis in trophoblast cells and its underlying mechanisms.In vitro, hypoxia/reoxygenation was applied to human trophoblast HTR-8/SVneo cells to model ischemic injury. ZFP36 was found to inhibit oxidative stress and ferroptosis by suppressing nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Mechanistically, ZFP36 binds to the 3' untranslated regions (3'UTRs) ofNCOA4mRNA, promoting its degradation and thereby attenuating ferritinophagy.In vivo, lentiviral overexpression of ZFP36 in a rat model of PE (induced by reduced uteroplacental perfusion pressure) alleviated clinical symptoms and reduced NCOA4-mediated ferroptosis. Collectively, these results demonstrate that ZFP36 regulates ferroptosis by modulating NCOA4-dependent ferritinophagy, offering a potential therapeutic strategy for PE through targeting ferroptosis.

Keywords:  Ferroptosis; Preeclampsia; Trophoblast cells; ZFP36

DOI:  https://doi.org/10.1016/j.bcp.2026.117836
J Extracell Biol. 2026 Mar;5(3): e70122

Proteomic Epithelial-To-Mesenchymal Transition Signature in Fetoplacental Small Extracellular Vesicles of Early-Onset Preeclampsia.

Michaela Stoiber, Monika Horvat Mercnik, Birgit Hirschmugl, Barbara Darnhofer, Dominique Pernitsch, Barbara Leopold-Posch, Ursula Hiden, Dagmar Kolb, Christian Wadsack.

  Preeclampsia (PE), a hypertensive disorder in pregnancy, is linked to placental vascular remodelling, increasing risks of foetal growth restriction and long-term offspring health problems. The role of fetoplacental endothelial cell-derived extracellular vesicles (EVs) in PE remains underexplored. This study investigates whether EV composition in Early-Onset PE (EO-PE) is altered, potentially contributing to impaired foetal development. Small EVs (sEVs) were isolated from primary fetoplacental endothelial cells (fpECs) of term (T), preterm (PT) and EO-PE pregnancies. sEVs were characterised using transmission electron microscopy, nanoparticle tracking analysis and Western blotting, confirming spherical morphology, size (<200 nm) and expression of canonical EV and endothelial markers. Proteomic profiling via nano-LC MS/MS and gene set enrichment analysis revealed a cohesive proteomic profile in fpEC-derived T- and PT-sEVs, but EO-PE-derived sEVs showed heterogeneity and functional alterations compared to T- and PT-derived sEVs. Notably, EO-PE-sEVs were enriched in proteins affiliated to epithelial-to-mesenchymal transition and myogenesis, processes tied to tissue remodelling and vascular homeostasis, all hallmarks in PE. This signature may represent a molecular signal associated with endothelial dysfunction. In contrast, T-sEVs were enriched in cell cycle and DNA repair pathways. These findings underscore the role of fetoplacental-derived EVs in placental-foetal communication under pathophysiological conditions.

Keywords:  extracellular vesicles; fetoplacental endothelial cells; foetal development; human placenta; preeclampsia; proteomics

DOI:  https://doi.org/10.1002/jex2.70122
Acta Physiol (Oxf). 2026 Apr;242(4): e70188

Kisspeptin Restores Placental mTOR Signaling and Improves Glucose Homeostasis Mediators Disrupted by Maternal Hypothyroidism in Rats.

Bianca Reis Santos, Jeane Martinha Dos Anjos Cordeiro, Luciano Cardoso Santos, Cleisla Souza Oliveira, Maria Clara Pascoal Santos Alvarez, Natália Panhoca Rodrigues, Jorge Lopez-Tello, Amanda N Sferruzzi-Perri, Rogéria Serakides, Juneo Freitas Silva.

   AIM: Reduced placental mTOR signaling is associated with intrauterine growth restriction and impaired maternal and placental metabolism. Since maternal hypothyroidism induces intrauterine growth restriction, and maternal treatment with kisspeptin-10 (Kp10) has been shown to improve feto-placental development in hypothyroid rats, this study aimed to evaluate the effects of maternal hypothyroidism, with and without kisspeptin-10 treatment, on maternal energy homeostasis and placental expression of mTOR and glucose metabolism mediators.
METHODS: Maternal hypothyroidism was induced by administration of propylthiouracil, and kisspeptin-10 treatment began on gestational day 8.
RESULTS: Maternal hypothyroidism caused glucose intolerance, decreased insulin and HDL levels, reduced fetal and placental weights, and thinned the placental interhaemal barrier. It also increased INSRβ and AKT, while downregulating placental p-mTOR/mTOR and Glut1. Although kisspeptin-10 treatment did not improve maternal glucose homeostasis or prevent feto-placental growth restriction, it attenuated maternal hypothyroidism-induced placental Glut1 dysregulation, upregulated the IGF1/IGF1R axis, and restored placental AKT/mTOR expression.
CONCLUSION: These findings suggest that kisspeptin-10 treatment in hypothyroid pregnant rats improves placental mTOR signaling and glucose metabolism mediators, highlighting novel pathways through which kisspeptin may modulate placental physiology.

Keywords:  Kiss1; PTU; fetus; glucose; metabolism; thyroid

DOI:  https://doi.org/10.1111/apha.70188
Cell Death Dis. 2026 Mar 02.

Deficient extravillous trophoblast invasion caused by impaired sialylation-Siglec-7 interaction contributes to recurrent pregnancy loss.

Linyu Zhang, Ying Feng, Peng Wu, Liuyan Chen, Nan Jiang, Xue Ma, Qianhong Ma, Hao-Jie Lu, Xue Xiao, Fang Ma.

Successful pregnancy requires precise immune interactions between fetal extravillous trophoblasts (EVT) and maternal decidual immune cells at the maternal-fetal interface. Glycosylation, particularly terminal sialylation, is emerging as a key modulator of these interactions; however, its functional role in regulating the EVT-immune crosstalk remains poorly defined. Here, we aimed to identify a critical sialic acid-Siglec-7-IL-8-STAT3 signaling axis that promotes EVT invasiveness and is disrupted during recurrent pregnancy loss (RPL). Using primary human tissues and organ-on-chip models, we demonstrate that EVTs from patients with RPL exhibit reduced sialylation, coinciding with an increased proportion of Siglec-7⁺ decidual natural killer (dNK) cells. Mechanistically, sialylated glycoproteins on EVT surfaces engage Siglec-7, stimulating IL-8 secretion by dNK cells, which, in turn, activates STAT3 in EVTs to enhance migration and invasion. Restoration of EVT sialylation re-engages Siglec-7, rescues IL-8-STAT3 signaling, and restores invasive capacity. Our findings reveal that defective EVT sialylation disrupts a key immunological checkpoint that normally promotes EVT invasion and potentially contributes to RPL. This work provides direct mechanistic evidence that specific glycan-encoded immune signals at the maternal-fetal interface are critical for healthy pregnancy outcomes and suggests that modulating sialylation may offer a therapeutic strategy for RPL.Proposed model of sialic acid-Siglec-7-mediated regulation of EVT invasion through the ST6GALNAC6-sialic acid-Siglec-7-IL-8-STAT3 signaling axis. Schematic representation of the working model: enhanced sialylation of EVT membrane glycoproteins-driven by ST6GALNAC6-facilitates recognition by Siglec-7 expressed on dNK cells. This interaction promotes the activation of the IL-8-STAT3 signaling pathway, which supports EVT cell migration and invasion. Disruption of sialylation or Siglec-7 engagement impairs this pathway and reduces EVT invasiveness, potentially contributing to the pathogenesis of RPL. Figure created with BioRender.com (https://BioRender.com/dxxt5az).

DOI: https://doi.org/10.1038/s41419-026-08503-9