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In this study, we found that the transcripts of BMP8 genes are enriched in the ovaries of humans and rodents. When analyzing transcriptomic datasets obtained from human mature granulosa cells, we further found that the BMP8 transcripts not only show the highest abundance among the searchable BMP-related ligands but also decrease significantly in women of advanced age or women with polycystic ovarian syndrome. The correlation between the BMP8 levels in granulosa cells and the decline in ovarian function in these subjects suggests that BMP8 protein may be involved in the regulation of granulosa cell function(s). Using a rat model, we demonstrated that human BMP8A protein activates the SMAD1\/5\/8 and the SMAD2\/3 pathways simultaneously in both immature and mature granulosa cells. Furthermore, the expression of potential type I and type II receptors used by BMP8 in rat granulosa cells was characterized. We found that BMP8A treatment can significantly inhibit gonadotropin-induced progesterone production and steroidogenesis-related gene expression in granulosa cells. Pathway dissection using receptor inhibitors further revealed that such inhibitory effects occur specifically through the BMP8-activated SMAD1\/5\/8, but not SMAD2\/3, pathway. Taken together, considering its abundance and possible functions in granulosa cells, we suggest that BMP8 may act as a novel luteinization inhibitor in growing follicles.<\/jats:p>","DOI":"10.1530\/rep-19-0305","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T11:43:42Z","timestamp":1580125422000},"page":"315-324","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":10,"title":["Human BMP8A suppresses luteinization of rat granulosa cells via the SMAD1\/5\/8 pathway"],"prefix":"10.1093","volume":"159","author":[{"given":"Fang-Ju","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences , National Yang-Ming University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences , National Yang-Ming University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences , National Yang-Ming University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,3,1]]},"reference":[{"key":"2026010712220864000_bib1","doi-asserted-by":"publisher","first-page":"E365","DOI":"10.1210\/jc.2014-2496","article-title":"Recombinant BMP4 and BMP7 downregulate PENTRAXIN 3 in human granulosa cells","author":"Chang","year":"2015","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2026010712220864000_bib2","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1210\/me.2013-1233","article-title":"BMP15 suppresses progesterone production by down-regulating StAR via ALK3 in human granulosa 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