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The proliferation of these cells and the synthesis of steroid hormones are crucial for follicular development and atresia. In our study, GCs were isolated using follicular fluid aspiration and subsequently identified through immunofluorescence. We investigated the impact of varying concentrations of N\u2010acetylcysteine (NAC) at 50, 100, 500, and 1000\u2009\u03bcmol\/L on sheep GCs, focusing on antioxidant levels, proliferation, apoptosis, and steroid hormone secretion. The phosphoinositide 3\u2010kinase (PI3K)\/protein kinase B (Akt) inhibitor LY294002 was used to explore the molecular mechanism of NAC on GCs proliferation and steroid hormone secretion in sheep. Our findings indicate that all concentrations of NAC tested promoted GC proliferation and suppressed apoptosis in sheep GCs. Notably, 100\u2009\u03bcmol\/L NAC exhibited the most pronounced effect on GC proliferation after 48\u2009h. The expression levels of CCND1, CDK4, and Bcl\u20102 were significantly elevated in all NAC concentration groups, whereas Bax expression was notably reduced. Furthermore, all NAC concentrations led to a significant reduction in reactive oxygen species (ROS) levels and an increase in the expression of CAT and SOD1. NAC also significantly enhanced the expression of CYP19A1 and 3\u03b2\u2010HSD, as well as the secretion of estradiol (E2) and progesterone (P4) by GCs. In summary, NAC activates the PI3K\/AKT signalling pathway, thereby promoting the proliferation of GCs and the secretion of E2 and P4 by sheep GCs in\u00a0vitro.<\/jats:p>","DOI":"10.1111\/rda.70006","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T07:04:03Z","timestamp":1737183843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanism of N\u2010Acetylcysteine Regulating Proliferation and Hormone Secretion of Granulosa Cells in Sheep"],"prefix":"10.1111","volume":"60","author":[{"given":"Jine","family":"Wang","sequence":"first","affiliation":[{"name":"College of Life Science and Engineering Northwest Minzu University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahua","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Science and Engineering Northwest Minzu University  Lanzhou Gansu 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