Lipid metabolism abnormalities induced by elevated PCSK9 in PCOS mice lead to ovarian granulosa cell apoptosis via AMPK and GSK-3β

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder among women of childbearing age, significantly impacting their fertility needs. Granulosa cell apoptosis in the ovaries is one of the primary factors affecting follicular growth and development as well as oocyte maturation in PCOS, yet its pathological mechanisms remain unclear. Our previous research revealed that elevated PCSK9 expression in PCOS mice affects ovarian function. This study further investigated the relationship between PCSK9 overexpression and ovarian granulosa cells using PCOS model mice and primary follicles. Results demonstrated that elevated PCSK9 levels induce lipid metabolism abnormalities in PCOS mice, subsequently activating AMP-activated protein kinase (AMPK) and glycogen synthase kinase 3 beta (GSK-3β) within follicles. This activation triggers granulosa cell apoptosis, ultimately impairing ovarian function. This discovery enriches the understanding of the pathological mechanisms underlying ovarian granulosa cell apoptosis in PCOS and provides novel therapeutic insights and targets for clinical management of PCOS patients.