Elevated IGFBP7 expression in follicular granulosa cells promotes PCOS pathogenesis.

Polycystic ovary syndrome (PCOS) can result in female infertility, menstrual irregularities, metabolic disturbances, hormonal imbalances, and significantly impact the reproductive health of women of childbearing age. Hyperandrogenism and insulin resistance are typical primary endocrine features of PCOS, which are also regarded as its core pathogenesis. In this study, IGFBP7 expression in granulosa cells (GCs) from women with and without PCOS was analyzed using bulk RNA-seq. A PCOS-like mouse model was constructed using dehydroepiandrosterone in IGFBP7 knockout and wild-type mice to explore the role of IGFBP7 in PCOS. Primary GCs from mice were cultured and transfected with IGFBP7 overexpression plasmid and siRNA fragments. Proliferation, apoptosis, and steroid hormone levels were measured to investigate the effects of IGFBP7 on granulosa cells. IGFBP7 expression was found to be elevated in patients with PCOS. Following IGFBP7 knockdown in mouse GC, there was a significant increase in GC proliferation, a decrease in GC apoptosis, and a notable decrease in testosterone secretion by GC. Conversely, overexpression of IGFBP7 in mouse granulosa cells significantly inhibited GC proliferation, significantly increased GC apoptosis, and led to a marked increase in testosterone secretion by GCs. With mouse model, a reduction in PCOS symptoms in mice after IGFBP7 deletion was observed. Elevated IGFBP7 expression in PCOS granulosa cells may induce apoptosis, hinder insulin signaling, and enhance androgen synthesis. These insights offer novel avenues for understanding and treating PCOS.