ArticleProceedings of the National Academy of Sciences of the United States of America2016
Uterine ALK3 is essential during the window of implantation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Decoding adenomyosis pathogenesis using an assembloid model.Science China. Life sciences · 2026Article
- Prenatally androgenized PCOS mice have ovary-independent uterine dysfunction and placental inflammation aggravated by high-fat diet.Science advances · 2025Article
- The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner.Nature communications · 2025Article
- Integral Roles of the TGFβ Signaling Pathway in Uterine Function and Disease.Endocrinology · 2025Review
- The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice.Aging cell · 2024Article
- Uterine cyclin A2-deficient mice as a model of female early pregnancy loss.The Journal of clinical investigation · 2024Article
- Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview.Cells · 2024Review
- Article
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.Communications biology · 2024Article
- Molecular mechanism of aberrant decidualization in adenomyosis leading to reduced endometrial receptivity.Frontiers in endocrinology · 2024Review
- Endometrial TGFβ signaling fosters early pregnancy development by remodeling the fetomaternal interface.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Review
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.Research square · 2023Article
- Events Leading to the Establishment of Pregnancy and Placental Formation: The Need to Fine-Tune the Nomenclature on Pregnancy and Gestation.International journal of molecular sciences · 2023Review
- The role of mesenchymal estrogen receptor 1 in mouse uterus in response to estrogen.Scientific reports · 2023Article
- Progress on the Role of Estrogen and Progesterone Signaling in Mouse Embryo Implantation and Decidualization.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- SMAD2/3 signaling in the uterine epithelium controls endometrial cell homeostasis and regeneration.Communications biology · 2023Article
- Transcriptomic profiling of canine decidualization and effects of antigestagens on decidualized dog uterine stromal cells.Scientific reports · 2022Article
- Role of EZH2 in Uterine Gland Development.International journal of molecular sciences · 2022Article
- The role of BMP4 signaling in trophoblast emergence from pluripotency.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
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Abstract
The window of implantation is defined by the inhibition of uterine epithelial proliferation, structural epithelial cell remodeling, and attenuated estrogen (E2) response. These changes occur via paracrine signaling between the uterine epithelium and stroma. Because implantation defects are a major cause of infertility in women, identifying these signaling pathways will improve infertility interventions. Bone morphogenetic proteins (BMPs) are TGF-β family members that regulate the postimplantation and midgestation stages of pregnancy. In this study, we discovered that signaling via activin-like kinase 3 (ALK3/BMPR1A), a BMP type 1 receptor, is necessary for blastocyst attachment. Conditional knockout (cKO) of ALK3 in the uterus was obtained by producing Alk3(flox) (/flox)-Pgr-cre-positive females. Alk3 cKO mice are sterile and have defects in the luminal uterine epithelium, including increased microvilli density and maintenance of apical cell polarity. Moreover, Alk3 cKO mice exhibit an elevated uterine E2 response and unopposed epithelial cell proliferation during the window of implantation. We determined that dual transcriptional regulation of Kruppel-like factor 15 (Klf15), by both the transforming growth factor β (TGF-β) transcription factor SMAD family member 4 (SMAD4) and progesterone receptor (PR), is necessary to inhibit uterine epithelial cell proliferation, a key step for embryo implantation. Our findings present a convergence of BMP and steroid hormone signaling pathways in the regulation of uterine receptivity.
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