{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T02:41:55Z","timestamp":1770345715011,"version":"3.49.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD072972"],"award-info":[{"award-number":["R01HD072972"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Characterization of the molecular factors regulating early embryonic development and their functional mechanisms is critical for understanding the causes of early pregnancy loss in monotocous species (cattle, human). We previously characterized a stage specific functional role of follistatin, a TGF-beta superfamily binding protein, in promoting early embryonic development in cattle. The mechanism by which follistatin mediates this embryotropic effect is not precisely known as follistatin actions in cattle embryos are independent of its classically known activin inhibition activity. Apart from activin, follistatin is known to bind and modulate the activity of the bone morphogenetic proteins (BMPs), which signal through SMAD1\/5 pathway and regulate several aspects of early embryogenesis in other mammalian species. Present study was designed to characterize the activity and functional requirement of BMP signaling during bovine early embryonic development and to investigate if follistatin involves BMP signaling for its stage specific embryotropic actions. Immunostaining and western blot analysis demonstrated that SMAD1\/5 signaling is activated after embryonic genome activation in bovine embryos. However, days 1\u20133 follistatin treatment reduced the abundance of phosphorylated SMAD1\/5 in cultured embryos. Inhibition of active SMAD1\/5 signaling (8\u201316 cell to blastocyst) using pharmacological inhibitors and\/or lentiviral-mediated inhibitory SMAD6 overexpression showed that SMAD1\/5 signaling is required for blastocyst production, first cell lineage determination as well as mRNA and protein regulation of TE (CDX2) cell markers. SMAD1\/5 signaling was also found to be essential for embryotropic actions of follistatin during days 4\u20137 but not days 1\u20133 of embryo development suggesting a role for follistatin in regulation of SMAD1\/5 signaling in bovine embryos.<\/jats:p>","DOI":"10.1093\/biolre\/ioz235","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T05:46:38Z","timestamp":1579671998000},"page":"795-805","source":"Crossref","is-referenced-by-count":10,"title":["Role of bone morphogenetic protein signaling in bovine early embryonic development and stage specific embryotropic actions of follistatin\u2020"],"prefix":"10.1093","volume":"102","author":[{"given":"Sandeep K","family":"Rajput","sequence":"first","affiliation":[{"name":"Laboratory of Mammalian Reproductive Biology and Genomics, Michigan State University, East Lansing, Michigan, USA"},{"name":"Colorado Center for Reproductive Medicine (CCRM), Lone Tree, CO 80124, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Yang","sequence":"first","affiliation":[{"name":"Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Science, Nanning, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Ashry","sequence":"first","affiliation":[{"name":"Laboratory of Mammalian Reproductive Biology and Genomics, Michigan State University, East Lansing, Michigan, USA"},{"name":"Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph K","family":"Folger","sequence":"first","affiliation":[{"name":"Laboratory of Mammalian Reproductive Biology and Genomics, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason G","family":"Knott","sequence":"first","affiliation":[{"name":"Developmental Epigenetics Laboratory, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George W","family":"Smith","sequence":"first","affiliation":[{"name":"Laboratory of Mammalian 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