ArticleEndocrinology2013
WNT4 acts downstream of BMP2 and functions via β-catenin signaling pathway to regulate human endometrial stromal cell differentiation.
Article in Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 126 citations in OpenAlex.
- Mesenchymal-epithelial transition supports rapid repair of the endometrial epithelium during postpartum uterine regeneration.Communications biology · 2026Article
- Multi-omics biomarkers in female fertility: from oocyte quality to endometrial receptivity and clinical translation.Biomarker research · 2026Review
- Dorsoventral-mediatedeLife · 2026Article
- Impact of vitamin D deficiency on defective endometrial decidualization and the repressive role of vitamin D receptor (VDR) in the epigenomic network.bioRxiv : the preprint server for biology · 2025Article
- Balancing Decidualization, Autophagy, and Cellular Senescence for Reproductive Success in Endometriosis Biology.International journal of molecular sciences · 2025Review
- Endometrial stromal Menin supports endometrial receptivity by maintaining homeostasis of WNT signaling pathway through H3K4me3 during WOI.Communications biology · 2025Article
- The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Endometrial aging is accompanied by H3K27ac and PGR loss.Nature aging · 2025Article
- Progesterone receptor in uterine glands is required for pregnancy establishment in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview.Cells · 2024Review
- The Long Non-Coding RNA GeneCells · 2024Article
- Establishment of Murine Pregnancy Requires the Promyelocytic Leukemia Zinc Finger Transcription Factor.International journal of molecular sciences · 2024Article
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.Communications biology · 2024Article
- ATOH8 Expression Is Regulated by BMP2 and Plays a Key Role in Human Endometrial Stromal Cell Decidualization.Endocrinology · 2023Article
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.Research square · 2023Article
- Exposure to di-isononyl phthalate during early pregnancy disrupts decidual angiogenesis and placental development in mice.Reproductive toxicology (Elmsford, N.Y.) · 2023Article
- Genetic variants associated with spontaneous preterm birth in women from India: a prospective cohort study.The Lancet regional health. Southeast Asia · 2023Article
- Fractalkine Improves the Expression of Endometrium Receptivity-Related Genes and Proteins at Desferrioxamine-Induced Iron Deficiency in HEC-1A Cells.International journal of molecular sciences · 2023Article
- DNA Methylation of Window of Implantation Genes in Cervical Secretions Predicts Ongoing Pregnancy in Infertility Treatment.International journal of molecular sciences · 2023Article
- Energy metabolism and maternal-fetal tolerance working in decidualization.Frontiers in immunology · 2023Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Differentiation of endometrial stromal cells into decidual cells is a prerequisite for successful embryo implantation. Our previous studies in the mouse have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGFβ superfamily, is essential for this differentiation process. BMP2 is markedly induced in human primary endometrial stromal cells (HESCs) as they undergo differentiation in response to steroid hormones and cAMP. The present study was undertaken to identify the BMP2-mediated molecular pathways in primary cultures of HESCs during decidualization. Using gene expression profiling, we identified wingless-related murine mammary tumor virus integration site 4 (WNT4) as a target of BMP2 regulation during decidualization. Attenuation of WNT4 expression in HESCs by small interfering RNA administration greatly reduced BMP2-induced stromal differentiation. Additionally, adenovirus-mediated overexpression of WNT4 in HESCs markedly advanced the differentiation program, indicating that it is a key regulator of decidualization. The stimulatory effect of WNT4 was accompanied by the accumulation of active β-catenin in the nuclei of decidualizing stromal cells, indicating the involvement of the canonical WNT signaling pathway. Functional inhibition of WNT4/β-catenin pathway by Dickkopf-1, an inhibitor of the canonical WNT signaling, or small interfering RNA-mediated silencing of β-catenin expression, greatly reduced the BMP2- and WNT4-induced decidualization. Gene expression profiling revealed that Forkhead box protein O1, a forkhead family transcription factor and previously reported regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. Taken together, these studies uncovered a linear pathway involving BMP2, WNT4/β-catenin, and Forkhead box protein O1 that operates in human endometrium to critically control decidualization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.