bims-placeb Biomed News
on Placental cell biology
Issue of 2026–01–25
eleven papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences
  1. Transient inhibition of MEK/ERK and WNT pathways enhances direct differentiation of primed hPSCs into functional trophoblast stem cells.
  2. Modeling human placental biology: a review of organoid technologies.
  3. The placenta at term: insights from the Loke Centre for Trophoblast Research 18th Annual Meeting, 2025.
  4. CRISPR/Cas9-mediated SLC2A1 gene knockout changes in energy metabolism and cellular behavior in human trophoblasts.
  5. Fetal growth restriction and preeclampsia as endpoints of a spectrum from the viewpoint of placental histopathology.
  6. Partial embryo loss caused by disruption of the placental hormone CTRP6 coincides with dNK cell abnormalities during pregnancy.
  7. Amyloid-β fibrils accumulated in preeclamptic placentas suppress cytotrophoblast syncytialization.
  8. Epigenetic, histological and clinical characterization of preeclampsia in oocyte donation pregnancies: insights into immune dysregulation and microRNA-mediated pathways.
  9. Discovery of New Markers for Haemogenic Endothelium and Haematopoietic Progenitors in the Mouse Yolk Sac.
  10. Glycolysis is intrinsically required in the follicle stem cell lineage but not in female germline stem cells or their early progeny in Drosophila melanogaster.
  11. Single-cell omics uncover gene dynamics shaping embryonic and extra embryonic lineages in pig blastocysts.
  1. Cell Regen. 2026 Jan 20. 15(1): 4
    Transient inhibition of MEK/ERK and WNT pathways enhances direct differentiation of primed hPSCs into functional trophoblast stem cells.
    Qifan Jiang, Ping Liu, Chunlin Chen.
      The placenta plays a pivotal role in human pregnancy, yet research into placental development has been hindered by limited access to early-stage embryos and ethical constraints. Although human trophoblast stem cells (hTSCs) have been established from blastocysts, deriving these cells efficiently from primed human pluripotent stem cells (hPSCs) remains challenging. Here, we developed a simplified and efficient strategy that enables direct, efficient conversion of primed hPSCs into stable, self-renewing hTSCs by transiently inhibiting the MEK/ERK signaling pathway using the inhibitor PD0325901 in a simplified basal medium. This approach significantly enhanced the generation of trophoblast cells expressing the critical trophoblast marker GATA3 and led to the establishment of homogeneous hTSC lines with robust capacities to differentiate into functional extravillous trophoblast (EVT) and syncytiotrophoblast (STB) lineages. Transcriptomic and chromatin accessibility analyses confirmed that these hTSCs closely resembled blastocyst-derived trophoblast cells and clearly differed from amnion lineages, confirming authentic trophoblast identity distinct from amnion. Additionally, precise modulation of WNT signaling activity was essential for optimal trophoblast induction efficiency, highlighting the importance of signaling equilibrium in trophoblast differentiation. Collectively, our optimized protocol offers an accessible and reproducible platform for modeling early placental development and understanding the pathogenesis of trophoblast-associated disorders in vitro.
    Keywords:  Differentiation; Human pluripotent stem cells; Human trophoblast stem cells; Placenta; Signaling
    DOI:  https://doi.org/10.1186/s13619-025-00261-x
  2. Front Cell Dev Biol. 2025 ;13 1693923
    Modeling human placental biology: a review of organoid technologies.
    Alaijah Bashi, Tyana Joseph, Viviane Schuch, Erica L Johnson.
      The development of placental organoids represents a significant breakthrough in reproductive biology, offering an advanced platform for studying human placental development and function. Unlike traditional two-dimensional (2D) cell cultures, three-dimensional (3D) organoid models, such as primary trophoblast organoids (TOs), JEG-3 organoids, and stem cell-derived organoids, provide a more robust and physiologically relevant environment. These models enable researchers to mimic the human placenta's complex architecture and cellular interactions. As a result, these advanced models promise to reveal the mechanisms underlying placental development and the associated disorders. This review compares different organoid types, highlighting their unique features and applications in studying trophoblast invasion, syncytialization, and placental barrier function. Bioinformatics approaches, particularly transcriptomic analyses, have been crucial in validating these models and identifying stage-specific markers of placental development. With challenges such as standardization issues and ethical considerations persisting, the integration of multiple organoid models, advanced technologies, and computational analyses currently provides the most comprehensive strategy for mimicking placental development across all stages in-vivo. Future directions for organoid technologies include the development of multi-organ-on-a-chip models and personalized medicine applications. This review concludes that while no single method perfectly replicates all stages of placental development, the combination of various 3D organoid models, supported by advanced technologies and computational analyses, offers the most effective approach to studying placental biology in-vivo.
    Keywords:  maternal–fetal interface; organoids; placenta; stem cell; trophoblast models
    DOI:  https://doi.org/10.3389/fcell.2025.1693923
  3. Biol Open. 2026 Jan 01. pii: bio062284. [Epub ahead of print]15(1):
    The placenta at term: insights from the Loke Centre for Trophoblast Research 18th Annual Meeting, 2025.
    Noa Hasky.
      The Loke Centre for Trophoblast Research Annual Meeting, 'The Placenta at Term', was held on 7-8 July, 2025, at the University of Cambridge, UK. The meeting brought together leading clinical and basic scientists from around the world to explore how robust research methods can improve understanding of placental complications such as preeclampsia, fetal growth restriction, and gestational diabetes. This Meeting Review highlights emerging research directions and emphasises the remarkable potential of the placenta, not only as a window into obstetrical complications, but also as a diagnostic tool for predicting the short- and long-term health of both mother and child.
    Keywords:  Fetal growth restriction; Gestational diabetes; Preeclampsia
    DOI:  https://doi.org/10.1242/bio.062284
  4. Reproduction. 2026 Jan 23. pii: xaag006. [Epub ahead of print]
    CRISPR/Cas9-mediated SLC2A1 gene knockout changes in energy metabolism and cellular behavior in human trophoblasts.
    Hahyun Park, Seung-Min Bae, Taeyeon Hong, Gwonhwa Song, Whasun Lim.
      Glucose transport across the placenta is essential for fetal growth and development. Glucose transporter 1 (GLUT1), encoded by the SLC2A1 gene, plays a central role in mediating maternal-fetal glucose exchange. Dysregulation of placental glucose transport is implicated in pregnancy-related complications, such as preeclampsia and fetal growth restriction (FGR); however, the mechanistic role of SLC2A1 in trophoblast function remains poorly defined. To functionally validate the role of SLC2A1 in human trophoblasts, we used CRISPR/Cas9-mediated knockout of the SLC2A1 gene, enabling complete and permanent loss of SLC2A1 expression. In the resulting SLC2A1 knockout (KO) human trophoblast HTR8/SVneo cells, SLC2A1 depletion induced a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS), leading to increased mitochondrial respiration, ATP production, mitochondrial calcium overload, and elevated mitochondrial ROS generation. These changes were accompanied by enhanced endoplasmic reticulum (ER) stress, as shown by the upregulation of p-PERK, IRE1α, and GRP78, as well as increased autophagic activity indicated by LC3B-II and p62 accumulation. Notably, mTOR signaling was also upregulated, suggesting a feedback loop that regulates autophagy. The loss of SLC2A1 impaired the PI3K/AKT pathway, reduced trophoblast migration and 3D spheroid formation, and disrupted epithelial-mesenchymal transition (EMT)-like properties. These findings demonstrate that SLC2A1 is essential for maintaining trophoblast energy homeostasis, redox balance, and invasive capacity; its deficiency triggers mitochondrial and ER stress responses that may contribute to placental dysfunction during early pregnancy.
    Keywords:  CRISPR/Cas9; SLC2A1; Trophoblasts; autophagy; metabolic reprogramming
    DOI:  https://doi.org/10.1093/reprod/xaag006
  5. Minerva Obstet Gynecol. 2026 Jan 19.
    Fetal growth restriction and preeclampsia as endpoints of a spectrum from the viewpoint of placental histopathology.
    István Dankó, András Tankó, Edit Kelemen, Gábor Cserni.
       BACKGROUND: We evaluated the common histopathological characteristics of preeclampsia (PE) and fetal growth restriction (FGR), and demonstrated the major differences of the three groups of 1/ PE with FGR, 2/ PE without FGR and 3/ FGR without PE.
    METHODS: Placental slides were studied retrospectively. Predominantly FGR- and PE-associated lesions were identified. Gestational age at the time of delivery (GATD) and diagnosis-to-delivery time (DTDT) were also examined.
    RESULTS: Decidual arteriopathies, maternal hypertension and obesity were more common in PE, and villous capillarization was significantly lower in FGR. We found that only villous infarction and chorangiosis had a connection with GATD. Villous infarction and chorangiosis were associated with DTDT >80 days, while placental changes leading to decreased villous capillarization was associated with DTDT <30 days.
    CONCLUSIONS: Despite several common histopathological characteristics, placental histopathological profile of PE with FGR, PE without FGR and FGR without PE have remarkable differences, indicating histological background of their distinguished prognosis. Inadequate vascular development and decidual vasculopathies are characteristic in PE, while the undercapillarization of placental villous tree and villitis of unknown etiology leading to placental damage are characteristic of FGR. The dynamic equilibrium of different entities determines global placental function, and manifestation of FGR and/or PE.
    DOI:  https://doi.org/10.23736/S2724-606X.25.05779-3
  6. iScience. 2026 Jan 16. 29(1): 114434
    Partial embryo loss caused by disruption of the placental hormone CTRP6 coincides with dNK cell abnormalities during pregnancy.
    Hairui Fan, Xiaolei Chen, Cui Du, Shuai Chen, Wenzhe Yu, Yuchen Tang, Yifu Wang, Haifei Wang, Wenbin Bao, Bin Cao, Ming-An Sun.
      The proper embryo maintenance depends on tight maternal-fetal communications. C1q/TNF-related protein 6 (C1qtnf6)-encoding a hormone-like CTRP6 protein-exhibits placenta-enriched expression and its deficiency causes partial fetal loss. Here, we demonstrate that abundant C1qtnf6 expression is distinctive for hemochorial placentae, which have deep uterine invasion. C1qtnf6 is most highly expressed in human extravillous trophoblasts and mouse spiral artery-associated trophoblast giant cells, which are functionally analogous cells that invade uterines. The partial embryo loss is mainly due to impaired CTRP6 production by placenta, and key natural killer effectors in maternal-fetal interface (MFI) are impaired by C1qtnf6-deficiency. C1qtnf6-deficiency simultaneously impairs the amount and effector production of decidual NK (dNK) cells, yet the placental structure and spiral artery remodeling appear normal. CTRP6 injection rescues the dNK cell abnormality and alleviates embryo loss. Overall, the partial embryo loss by CTRP6-deficiency coincides with dNK cell abnormality, which highlights the importance of MFI immune microenvironment for embryo maintenance.
    Keywords:  biological sciences; molecular biology
    DOI:  https://doi.org/10.1016/j.isci.2025.114434
  7. Life Sci Alliance. 2026 Apr;pii: e202503453. [Epub ahead of print]9(4):
    Amyloid-β fibrils accumulated in preeclamptic placentas suppress cytotrophoblast syncytialization.
    Kaho Nishioka, Midori Ikezaki, Naoyuki Iwahashi, Miyu Arakawa, Momo Fukushima, Noa Mori, Mika Mizoguchi, Yuko Horiuchi-Tanizaki, Megumi Fujino, Takami Tomiyama, Yoshito Ihara, Kenji Uchimura, Kazuhiko Ino, Kazuchika Nishitsuji.
      Cerebral deposition of fibrillar amyloid-β (Aβ) is a pathological hallmark of Alzheimer's disease. Although Aβ is present in human placentas and accumulates in preeclamptic placentas characterized by poor placentation, the production and role of Aβ in the human placenta remain unclear. Because hypoxia in mid-to-late pregnancy is a risk for preeclampsia, we found that levels of hypoxia-inducible factor 1-α and β-secretase (BACE-1) increased concurrently with placental Aβ deposition in late-stage preeclamptic placentas. We also found that a human cytotrophoblast (CTB) model, BeWo cells, actually produced Aβ species and that hypoxia increased Aβ production and BACE-1 protein levels. Aβ42 fibrils inhibited CTB syncytialization, a critical step in maintaining pregnancy, by inducing loss of membrane localization of cell-cell adhesion molecules. Primary human CTBs confirmed these observations. Taken together, our results suggest that increased Aβ production in CTBs by hypoxia may lead to the formation of Aβ fibrils, which inhibit syncytiotrophoblast formation and are detrimental to pregnancy. Thus, our results reveal the novel role of Aβ fibrils in the pathogenesis of preeclampsia.
    DOI:  https://doi.org/10.26508/lsa.202503453
  8. Front Cell Dev Biol. 2025 ;13 1718305
    Epigenetic, histological and clinical characterization of preeclampsia in oocyte donation pregnancies: insights into immune dysregulation and microRNA-mediated pathways.
    Irma Saulle, Maria Di Giminiani, Ozge Yazici, Claudio Fenizia, Manuela Nebuloni, Roberta Rossi, Mara Biasin, Valeria Savasi.
       Introduction: Preeclampsia (PE) is a hypertensive disorder in pregnancy, influencing global health risks due to its poorly understood aetiology involving immune mismatches. Oocyte Donation increases PE risk due to complete HLA incompatibility, leading to immune activation. MicroRNAs (miRNAs) emerged as crucial regulators in placental development, immune regulation, and endothelial function, acting as post-transcriptional gene regulators. This study aims to explore whether specific miRNAs, previously implicated in PE, can be used to distinguish preeclamptic and non-preeclamptic mothers undergoing oocyte donation pregnancy.
    Methods: This prospective study enrolled 20 mothers, divided into four groups: oocyte donation normotensive, oocyte donation preeclamptic, spontaneous normotensive, and spontaneous preeclamptic mothers. Maternal and cord blood samples were collected postpartum, along with placental biopsies. Tissue samples underwent histological examination. Total miRNAs were extracted from plasma, cord blood, and placenta and quantified via digital droplet PCR. The secretome analysis of cytokine/chemokines was performed on the mother's plasma and cord blood by Luminex ELISA.
    Results: In oocyte normotensive the epigenetic (miR-155, miR-17, miR-30) and immune profile (CXCL10, VEGF), displayed only limited variations compared to spontaneous normotensive. Conversely, preeclamptic oocyte recipients exhibited marked molecular dysregulation, characterized by significant upregulation of pro-inflammatory miRNAs (miR-155, miR-17, miR-223) and cytokines (IL-6, IL-1β, TNF-α, IFN-γ) in maternal plasma and placental tissue, indicating heightened immune activation. Notably, miR-30 and let-7c were downregulated. Intriguingly, miRNA expression in umbilical cord plasma was often inversely correlated with maternal and placental profiles, suggesting complex miRNA trafficking and fetal protection mechanisms. Placental histology showed minimal pathological changes in preeclamptic oocyte recipients, contrasting with more severe lesions in preeclamptic spontaneously conceived pregnancies, reflecting differing underlying pathogenic processes.
    Conclusion: This study highlights significant alterations in miRNA expression and cytokine profiles associated with PE, particularly in oocyte donation pregnancies. The findings suggested a complex interplay between maternal immune regulation and placental function, with distinct maternal and fetal immune responses. Understanding these molecular and immunological changes may facilitate the development of novel diagnostic biomarkers and targeted therapies to improve maternal and fetal outcomes in PE.
    Keywords:  cytokines; inflammation; miRNA; oocyte donation; preeclampsia
    DOI:  https://doi.org/10.3389/fcell.2025.1718305
  9. J Dev Biol. 2026 Jan 06. pii: 4. [Epub ahead of print]14(1):
    Discovery of New Markers for Haemogenic Endothelium and Haematopoietic Progenitors in the Mouse Yolk Sac.
    Guillermo Diez-Pinel, Alessandro Muratore, Christiana Ruhrberg, Giovanni Canu.
      Erythro-myeloid progenitors (EMPs) originate from the haemogenic endothelium in the yolk sac via an endothelial-to-haematopoietic transition (EHT) to generate blood and immune cells that support embryo development. Yet, the transitory nature of EHT and the limited availability of molecular markers have constrained our understanding of the origin, identity, and differentiation dynamics of EMPs. Here, we have refined the annotation of yolk sac haemato-vascular populations in publicly available single-cell RNA sequencing (scRNAseq) datasets from mouse embryos to identify novel molecular markers of haemogenic endothelium and EMPs. By sub-clustering key cell populations followed by pseudotime analysis, we refined cluster annotations and then reconstructed differentiation trajectories. Subsequent differential gene expression analysis between clusters identified novel cell surface markers for haemogenic endothelial cells (Fxyd5 and Scarf1) and EMPs (Fcer1g, Tyrobp, and Mctp1). Further, we have identified candidate signalling and metabolic pathways that may regulate yolk sac haematopoietic emergence and differentiation. The specificity of FXYD5, SCARF1, and FCER1G for haemogenic endothelium and EMPs was validated by immunostaining of the mouse yolk sac. These insights into the transcriptional dynamics in the yolk sac should support future investigation of EHT and haematopoietic differentiation during early mammalian development.
    Keywords:  EMPs; Fcer1g; Fxyd5/Dysadherin; Scarf1; erythro-myeloid progenitors; haematopoietic development; haematopoietic differentiation; haemogenic endothelium; mouse embryo; single-cell transcriptomic; yolk sac
    DOI:  https://doi.org/10.3390/jdb14010004
  10. Genetics. 2026 Jan 20. pii: iyag015. [Epub ahead of print]
    Glycolysis is intrinsically required in the follicle stem cell lineage but not in female germline stem cells or their early progeny in Drosophila melanogaster.
    Emily M Wessel, Daniela Drummond-Barbosa.
      Multiple tissue stem cells depend on glycolysis or β-oxidation for cell fate decisions. However, how universal these requirements are and how they change as stem cell daughters undergo differentiation remains unclear. The Drosophila ovary is a powerful stem cell model with two distinct stem cell populations: germline stem cells (GSCs), which produce oocytes to perpetuate the species, and follicle stem cells (FSCs), a somatic lineage. Several studies have begun addressing the roles of metabolism within the Drosophila female GSC lineage, but direct systematic analyses of glycolysis and/or mitochondrial fatty acid β-oxidation requirements across these lineages have been lacking. Here, using genetic mosaic analysis with null alleles, we found that genes encoding key regulatory glycolytic enzymes-Phosphofructokinase (Pfk) and Pyruvate kinase (Pyk)-are not cell autonomously required for GSC maintenance, proliferation, or early differentiation through 16-cell germline cyst formation and oocyte specification. Although germline cysts lacking Pfk or Pyk function can develop through early vitellogenesis, they grow slowly and display impaired nurse cell chromatin dispersal. By contrast, FSCs and their early daughters require Pfk (but not Pyk) for normal survival, while later follicle cells need both Pfk and Pyk for survival and only Pfk for proliferation, suggesting that follicle cells predominantly require glycolytic intermediates upstream of Pyk. Surprisingly, mitochondrial β-oxidation was dispensable in both lineages. These findings uncover an unusual metabolic state in GSCs and their early daughters, with marked differences from the neighboring FSC lineage and other somatic stem cells.
    Keywords:   Drosophila ; follicle stem cells; germline stem cells; glycolysis; oogenesis; β-oxidation
    DOI:  https://doi.org/10.1093/genetics/iyag015
  11. iScience. 2026 Jan 16. 29(1): 114519
    Single-cell omics uncover gene dynamics shaping embryonic and extra embryonic lineages in pig blastocysts.
    Adrien Dufour, Marie-Noëlle Rossignol, Patrick Manceau, Yoann Bailly, Stéphane Ferchaud, Marie-José Mercat, Ali G Turhan, Sarah Djebali, Sylvain Foissac, Jérôme Artus, Hervé Acloque.
      Late blastocyst development before implantation is a unique feature of ungulates, during which the epiblast proliferates and maintains pluripotency while extra-embryonic tissues expand dramatically, elongating to several tens of centimeters. The mechanisms coordinating these processes are not well understood. We performed single-cell omics profiling of porcine blastocysts from the hatched stage (E7) through early (E9) and late ovoid stages (E11). From 15,370 cells, we identified distinct embryonic and extra-embryonic populations with characteristic chromatin accessibility profiles. We reconstructed gene regulatory networks using enhancer-based eRegulons and validated them through motif occupancy analysis. Extra-embryonic tissues showed strong shifts in gene regulatory module activity at the onset of elongation, reflecting major transitions in morphogenesis and differentiation and the activation of pathways linked to cell morphology, proliferation, metabolism, trafficking, and biomolecule transport. In contrast, epiblast cells retained a stable transcriptional and regulatory identity from day 7 to day 11, immediately preceding the onset of gastrulation.
    Keywords:  developmental biology; embryology; epigenetics; model organism; transcriptomics
    DOI:  https://doi.org/10.1016/j.isci.2025.114519
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