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

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.