ArticleEndocrinology2014
SMAD1/5 signaling in the early equine placenta regulates trophoblast differentiation and chorionic gonadotropin secretion.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Comparative analysis of the transcriptome and methylome in distinct trophoblast populations at the time of embryo implantation in mares.BMC genomics · 2026Article
- The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Effects of Interleukin-6 (IL-6) on In Vitro Cultured Equine Chorionic Girdle Cells.Animals : an open access journal from MDPI · 2025Article
- Production of Mare Chorionic Girdle Organoids That Secrete Equine Chorionic Gonadotropin.International journal of molecular sciences · 2023Article
- The role of BMP4 signaling in trophoblast emergence from pluripotency.Cellular and molecular life sciences : CMLS · 2022Review
- Role of autocrine bone morphogenetic protein signaling in trophoblast stem cells†.Biology of reproduction · 2022Article
- The transcriptome landscapes of allantochorion and vitelline-chorion in equine day 30 conceptus.Frontiers in cell and developmental biology · 2022Article
- Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse.Scientific reports · 2020Article
- Role of bone morphogenetic protein signaling in bovine early embryonic development and stage specific embryotropic actions of follistatin†.Biology of reproduction · 2020Article
- Dynamic changes in gene expression and signalling during trophoblast development in the horseReproduction (Cambridge, England) · 2018Article
- Glial Cells Missing 1 Regulates Equine Chorionic Gonadotrophin Beta SubunitFrontiers in endocrinology · 2018Article
- Cadmium inhibits placental trophoblast cell migration via miRNA regulation of the transforming growth factor beta (TGF-β) pathway.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017Article
- Placentation in Equids.Advances in anatomy, embryology, and cell biologyArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
TGFβ superfamily proteins, acting via SMAD (Sma- and Mad-related protein)2/3 pathways, regulate placental function; however, the role of SMAD1/5/8 pathway in the placenta is unknown. This study investigated the functional role of bone morphogenetic protein (BMP)4 signaling through SMAD1/5 in terminal differentiation of primary chorionic gonadotropin (CG)-secreting trophoblast. Primary equine trophoblast cells or placental tissues were isolated from day 27-34 equine conceptuses. Detected by microarray, RT-PCR, and quantitative RT-PCR, equine chorionic girdle trophoblast showed increased gene expression of receptors that bind BMP4. BMP4 mRNA expression was 20- to 60-fold higher in placental tissues adjacent to the chorionic girdle compared with chorionic girdle itself, suggesting BMP4 acts primarily in a paracrine manner on the chorionic girdle. Stimulation of chorionic girdle-trophoblast cells with BMP4 resulted in a dose-dependent and developmental stage-dependent increase in total number and proportion of terminally differentiated binucleate cells. Furthermore, BMP4 treatment induced non-CG-secreting day 31 chorionic girdle trophoblast cells to secrete CG, confirming a specific functional response to BMP4 stimulation. Inhibition of SMAD2/3 signaling combined with BMP4 treatment further enhanced differentiation of trophoblast cells. Phospho-SMAD1/5, but not phospho-SMAD2, expression as determined by Western blotting was tightly regulated during chorionic girdle trophoblast differentiation in vivo, with peak expression of phospho-SMAD1/5 in vivo noted at day 31 corresponding to maximal differentiation response of trophoblast in vitro. Collectively, these experiments demonstrate the involvement of BMP4-dependent pathways in the regulation of equine trophoblast differentiation in vivo and primary trophoblast differentiation in vitro via activation of SMAD1/5 pathway, a previously unreported mechanism of TGFβ signaling in the mammalian placenta.
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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.