ArticleBMC biology2020
Hyperactivated Wnt-β-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2.
Article in BMC biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- USP22 suppresses trophoblast cell necroptosis in preeclampsia by stabilizing KAT2A-mediated histone acetylation at the SFRP1 promoter.Journal of translational medicine · 2026Article
- Placental nicotinamide adenine dinucleotide modulates the timing of labor.Science (New York, N.Y.) · 2026Article
- Advances in the Role of Adipose Tissue in Promoting Injury Repair and Resist Infection.Immunity, inflammation and disease · 2026Review
- Secreted frizzled-related protein 3 is associated with metabolic disturbances in gestational diabetes.Frontiers in endocrinology · 2026Article
- Secreted Frizzled-related proteins in animal development.Histochemistry and cell biology · 2025Review
- Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion.Cells · 2025Article
- The Expression Profile of Wnt/β-Catenin Signalling Pathway Genes in Miscarriages.Balkan journal of medical genetics : BJMG · 2025Article
- ASCL2 is a key regulator of the proliferation-differentiation equilibrium in the esophageal epithelium.Biology open · 2024Article
- Decoding the molecular pathways governing trophoblast migration and placental development; a literature review.Frontiers in endocrinology · 2024Review
- Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2024Article
- Article
- Sperm DNA methylation patterns at discrete CpGs and genes involved in embryonic development are related to bull fertility.BMC genomics · 2022Article
- Wnt4, Wnt6 and β-catenin expression in human placental tissue - is there a link with first trimester miscarriage? Results from a pilot study.Reproductive biology and endocrinology : RB&E · 2022Article
- Elevated Serum SFRP5 Levels During Preeclampsia and Its Potential Association with Trophoblast Dysfunction via Wnt/β-Catenin Suppression.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWnt signaling is a critical determinant for the maintenance and differentiation of stem/progenitor cells, including trophoblast stem cells during placental development. Hyperactivation of Wnt signaling has been shown to be associated with human trophoblast diseases. However, little is known about the impact and underlying mechanisms of excessive Wnt signaling during placental trophoblast development.
resultsIn the present work, we observed that two inhibitors of Wnt signaling, secreted frizzled-related proteins 1 and 5 (Sfrp1 and Sfrp5), are highly expressed in the extraembryonic trophoblast suggesting possible roles in early placental development. Sfrp1 and Sfrp5 double knockout mice exhibited disturbed trophoblast differentiation in the placental ectoplacental cone (EPC), which contains the precursors of trophoblast giant cells (TGCs) and spongiotrophoblast cells. In addition, we employed mouse models expressing a truncated β-catenin with exon 3 deletion globally and trophoblast-specifically, as well as trophoblast stem cell lines, and unraveled that hyperactivation of canonical Wnt pathway exhausted the trophoblast precursor cells in the EPC, resulting in the overabundance of giant cells at the expense of spongiotrophoblast cells. Further examination uncovered that hyperactivation of canonical Wnt pathway disturbed trophoblast differentiation in the EPC via repressing Ascl2 expression.
conclusionsOur investigations provide new insights that the homeostasis of canonical Wnt-β-catenin signaling is essential for EPC trophoblast differentiation during placental development, which is of high clinical relevance, since aberrant Wnt signaling is often associated with trophoblast-related diseases.
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