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They affect proliferation and apoptosis of granulosa cells (GC) and can influence whether small antral follicles continue their growth or undergo atresia. Transforming growth factor-alpha (TGF\u03b1), an oocyte-derived growth factor, is thought to regulate granulosa cell function; yet its investigation has been largely overshadowed by emerging interest in TGF-beta superfamily members, such as bone morphogenetic proteins (BMP) and anti-Mullerian hormone (AMH). Here, effects of TGF\u03b1 on bovine GC proliferation, intracellular signaling, and cytokine-induced apoptosis were evaluated. Briefly, all small antral follicles (3\u20135 mm) from slaughterhouse specimens of bovine ovary pairs were aspirated and the cells were plated in T25 flasks containing DMEM\/F12 medium, 10% FBS, and antibiotic-antimycotic, and incubated at 37 \u00b0C in 5% CO2 for 3 to 4 d. Once confluent, the cells were sub-cultured for experiments (in 96-, 12-, or 6-well plates) in serum-free conditions (DMEM\/F12 medium with ITS). Exposure of the bGC to TGF\u03b1 (10 or 100 ng\/mL) for 24 h stimulated cell proliferation compared to control (P\u2005&amp;lt;\u20050.05; n\u2005=\u20057 ovary pairs). Proliferation was accompanied by a concomitant increase in mitogen-activated protein kinase (MAPK) signaling within 2 h of treatment, as evidenced by phosphorylated ERK1\/2 expression (P\u2005&amp;lt;\u20050.05, n\u2005=\u20053 ovary pairs). These effects were entirely negated, however, by the MAPK inhibitor, U0126 (10uM, P\u2005&amp;lt;\u20050.05). Additionally, prior exposure of the bGC to TGF\u03b1 (100 ng\/mL) failed to prevent Fas Ligand (100 ng\/mL)-induced apoptosis, as measured by caspase 3\/7 activity (P\u2005&amp;lt;\u20050.05, n\u2005=\u20057 ovary pairs). Collectively, the results indicate TGF\u03b1 stimulates proliferation of bGC from small antral follicles via a MAPK\/ERK-mediated mechanism, but this action alone fails to prevent apoptosis, suggesting that TGF\u03b1 may be incapable of promoting their persistence in follicles during the process of follicular selection\/dominance.<\/jats:p>","DOI":"10.1093\/jas\/skac105","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:07:35Z","timestamp":1656634055000},"source":"Crossref","is-referenced-by-count":6,"title":["Stimulatory effects of TGF\u03b1 in granulosa cells of bovine small antral follicles"],"prefix":"10.1093","volume":"100","author":[{"given":"Allie L","family":"Lundberg","sequence":"first","affiliation":[{"name":"Orna Therapeutics , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole M","family":"Jaskiewicz","sequence":"additional","affiliation":[{"name":"Department of Animal and Veterinary Sciences, The University of Vermont , Burlington, VT 05405 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail M","family":"Maucieri","sequence":"additional","affiliation":[{"name":"Department of Animal and Veterinary Sciences, The University of Vermont , Burlington, VT 05405 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H","family":"Townson","sequence":"additional","affiliation":[{"name":"Department of Animal and Veterinary Sciences, The University of Vermont , Burlington, VT 05405 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,1]]},"reference":[{"key":"2023070101191676800_CIT0001","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1530\/jrf.0.0940177","article-title":"Association between surges of follicle-stimulating hormone and the emergence of follicular waves in heifers","volume":"94","author":"Adams","year":"1992","journal-title":"J. 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