ArticleProceedings of the National Academy of Sciences of the United States of America2015
Uterine activin receptor-like kinase 5 is crucial for blastocyst implantation and placental development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. 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, 72 citations in OpenAlex.
- Deciphering the maternal uterine signals that shape placenta development.Reproduction (Cambridge, England) · 2026Review
- Disruption of primary ciliary prostaglandin EJournal of biomedical science · 2026Article
- Maternal high-fat, high-sucrose diet-induced excess adiposity is linked to placental hypoxia and disruption of fetoplacental immune homeostasis in late gestation†.Biology of reproduction · 2025Article
- TGFBR2 coordinates the endometrial response to estrogen, regulating endometrial hyperplasia and fertility.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Diverse Roles of Tubulin Polymerization Promoting Protein 3 (TPPP3) in Human Health and Disease.Cells · 2025Review
- Human Decidual RUNX1 Promotes Angiogenesis and Trophoblast Differentiation by Regulating Extracellular Vesicle Signaling.Endocrinology · 2025Article
- Dual Role of Natural Killer Cells in Early Pregnancy: Immunopathological Implications and Therapeutic Potential in Recurrent Spontaneous Abortion and Recurrent Implantation Failure.Cell proliferation · 2025Review
- Integral Roles of the TGFβ Signaling Pathway in Uterine Function and Disease.Endocrinology · 2025Review
- Heterogeneous Cardiac-Derived and Neural Crest-Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis.Science (New York, N.Y.) · 2025Article
- Maternal RNA transcription in Dlk1-Dio3 domain is critical for proper development of the mouse placental vasculature.Communications biology · 2024Article
- A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis.Nature communications · 2024Article
- Article
- Endometrial TGFβ signaling fosters early pregnancy development by remodeling the fetomaternal interface.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Review
- Genomic Signatures Associated with Transitions to Viviparity in Cyprinodontiformes.Molecular biology and evolution · 2023Article
- Uterine-specificiScience · 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
- Uterine Deletion ofInternational journal of molecular sciences · 2022Article
- Gene silencing by EZH2 suppresses TGF-β activity within the decidua to avert pregnancy-adverse wound healing at the maternal-fetal interface.Cell reports · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Members of the transforming growth factor β (TGF-β) superfamily are key regulators in most developmental and physiological processes. However, the in vivo roles of TGF-β signaling in female reproduction remain uncertain. Activin receptor-like kinase 5 (ALK5) is the major type 1 receptor for the TGF-β subfamily. Absence of ALK5 leads to early embryonic lethality because of severe defects in vascular development. In this study, we conditionally ablated uterine ALK5 using progesterone receptor-cre mice to define the physiological roles of ALK5 in female reproduction. Despite normal ovarian functions and artificial decidualization in conditional knockout (cKO) mice, absence of uterine ALK5 resulted in substantially reduced female reproduction due to abnormalities observed at different stages of pregnancy, including implantation defects, disorganization of trophoblast cells, fewer uterine natural killer (uNK) cells, and impairment of spiral artery remodeling. In our microarray analysis, genes encoding proteins involved in cytokine-cytokine receptor interactions and NK cell-mediated cytotoxicity were down-regulated in cKO decidua compared with control decidua. Flow cytometry confirmed a 10-fold decrease in uNK cells in cKO versus control decidua. According to these data, we hypothesize that TGF-β acts on decidual cells via ALK5 to induce expression of other growth factors and cytokines, which are key regulators in luminal epithelium proliferation, trophoblast development, and uNK maturation during pregnancy. Our findings not only generate a mouse model to study TGF-β signaling in female reproduction but also shed light on the pathogenesis of many pregnancy complications in human, such as recurrent spontaneous abortion, preeclampsia, and intrauterine growth restriction.
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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.