抗缪勒氏管激素通过ESR2/p38丝裂原活化蛋白激酶信号通路调节绵羊颗粒细胞功能。

AMH regulates granulosa cell function via ESR2/ p38-MAPK signaling pathway in sheep.

作者信息

Xu Hui, Cai Yu, Yang Hua, Zhang Chong, Liu Wanru, Zhao Binru, Wang Feng, Zhang Yanli

机构信息

Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China.

出版信息

Commun Biol. 2025 May 29;8(1):824. doi: 10.1038/s42003-025-08259-6.

Anti-Müllerian Hormone (AMH), secreted by granulosa cells (GCs) of preantral follicles, regulates early-stage follicle growth by inhibiting the activation of primordial follicles. While GCs facilitate follicle development and ovulation through estrogen and progesterone secretion, the role of AMH in sheep GCs and its impact on follicle development remains unclear. Here, we show that exogenous AMH inhibits primordial follicle development utilizing in vitro culture of fetal sheep ovarian cortex model. Knockdown of AMH in sheep GCs increases cell proliferation, decreases apoptosis, and elevates estradiol (E2) secretion, while overexpression has the opposite effects. RNA-seq analysis suggests that AMH modulates genes involved in cell cycle regulation and MAPK signaling. Notably, AMH downregulates estrogen receptor β (ESR2) expression and suppresses FSH-induced upregulation of aromatase (CYP19A1). These findings demonstrate AMH regulates GCs function through multiple pathways, offering insights into sheep fertility and potential targets to enhance reproductive efficiency.

抗苗勒管激素（AMH）由窦前卵泡的颗粒细胞（GCs）分泌，通过抑制原始卵泡的激活来调节早期卵泡生长。虽然颗粒细胞通过分泌雌激素和孕酮促进卵泡发育和排卵，但AMH在绵羊颗粒细胞中的作用及其对卵泡发育的影响仍不清楚。在这里，我们利用胎羊卵巢皮质模型的体外培养表明，外源性AMH抑制原始卵泡发育。敲低绵羊颗粒细胞中的AMH可增加细胞增殖、减少细胞凋亡并提高雌二醇（E2）分泌，而过表达则产生相反的效果。RNA测序分析表明，AMH调节参与细胞周期调控和丝裂原活化蛋白激酶（MAPK）信号传导的基因。值得注意的是，AMH下调雌激素受体β（ESR2）表达并抑制促卵泡激素（FSH）诱导的芳香化酶（CYP19A1）上调。这些发现表明，AMH通过多种途径调节颗粒细胞功能，为绵羊生育能力及提高繁殖效率的潜在靶点提供了见解。