Anti-Müllerian hormone (AMH) is produced by ovarian granulosa cells (GCs)and plays a major role in inhibiting the recruitment of primordial follicles and reducing the sensitivity of growing follicles to follicle-stimulating hormone (FSH). Bone morphogenetic protein 6 (BMP6) has similar spatiotemporal expression to AMH during follicular development, suggesting that BMP6 may regulate AMH expression. However, the specific mechanism by which BMP6 regulates AMH expression remains unclear. The objectives of this study were to examine the molecular pathway by which BMP6 regulates AMH expression. The results showed that BMP6 promoted the secretion and expression of AMH in goat ovarian GCs. Mechanistically, BMP6 upregulated the expression of sex-determining region Y-box 9 (SOX9) and GATA-binding factor 4 (GATA4), which was associated with the transcriptional initiation of AMH. AMH expression was significantly decreased by GATA4 knockdown. Moreover, BMP6 treatment promoted the phosphorylation of SMAD1/5/8, whereas inhibiting the SMAD1/5/8 signaling pathway significantly abolished BMP6-induced upregulation of AMH and GATA4 expression. Interestingly, the activation of SMAD1/5/8 alone did not affect the expression of AMH or GATA4. The results suggested that BMP6 upregulated GATA4 through the SMAD1/5/8 signaling pathway, which in turn promoted AMH expression.

抗苗勒管激素 (AMH) 由卵巢颗粒细胞 (GCs) 产生，在抑制原始卵泡募集和降低生长卵泡对促卵泡激素 (FSH) 的敏感性方面起着重要作用。骨形态发生蛋白 6 (BMP6) 在卵泡发育过程中具有与 AMH 相似的时空表达，表明 BMP6 可能调节 AMH 表达。然而，BMP6调控AMH表达的具体机制尚不清楚。本研究的目的是检查 BMP6 调节 AMH 表达的分子途径。结果表明，BMP6促进山羊卵巢GCs中AMH的分泌和表达。从机制上讲，BMP6 上调了性别决定区 Y-box 9 (SOX9) 和 GATA 结合因子 4 (GATA4) 的表达，这与 AMH 的转录起始有关。GATA4 敲低显着降低了 AMH 表达。此外，BMP6 处理促进了 SMAD1/5/8 的磷酸化，而抑制 SMAD1/5/8 信号通路显着消除了 BMP6 诱导的 AMH 和 GATA4 表达上调。有趣的是，单独激活 SMAD1/5/8 并不影响 AMH 或 GATA4 的表达。结果表明，BMP6 通过 SMAD1/5/8 信号通路上调 GATA4，进而促进 AMH 表达。单独激活 SMAD1/5/8 不影响 AMH 或 GATA4 的表达。结果表明，BMP6 通过 SMAD1/5/8 信号通路上调 GATA4，进而促进 AMH 表达。单独激活 SMAD1/5/8 不影响 AMH 或 GATA4 的表达。结果表明，BMP6 通过 SMAD1/5/8 信号通路上调 GATA4，进而促进 AMH 表达。