Research progress on granulosa cell apoptosis in premature ovarian failure

Premature ovarian failure (POF) is a pathological condition characterised by the decline of ovarian function in women under the age of 40. It is closely associated with decreased fertility, elevated risks of osteoporosis and cardiovascular diseases, and has emerged as a significant clinical issue affecting women's reproductive health and quality of life. Current research indicates that granulosa cell (GC), as key components of the follicular microenvironment, can accelerate follicular atresia through abnormal apoptosis, thereby contributing to the onset and progression of POF. In recent years, advances in molecular biology and omics technologies have facilitated deeper investigation into the mechanisms of GC apoptosis. Studies have revealed that its regulation involves multi level factors: at the protein level, the BCL 2 family and the Caspase cascade constitute the core module of apoptosis execution; at the signaling pathway level, pathways such as Wnt/β catenin, death receptor signaling, Hippo, and PI3K/AKT/mTOR interact through crosstalk to coordinately regulate GC apoptosis. In addition, epigenetic modifications, oxidative stress, hormonal imbalances, and inflammatory microenvironments collectively contribute to the initiation and progression of GC apoptosis. Hence, this review systematically summaries the signaling pathways, key proteins, and underlying regulatory mechanisms related to GC apoptosis, to elucidate its role in the pathogenesis of POF. This work seeks to provide novel theoretical perspectives on the pathological mechanisms of POF and to offer a reference for developing targeted intervention strategies aimed at regulating GC apoptosis.