Downregulation of intracellular ATP levels by PANX1 inhibits ovarian granulosa cell proliferation and mediates follicular dysplasia in elderly women

This study examined pannexin 1 (PANX1) expression in ovarian granulosa cells of women with advanced maternal age and its role in cell proliferation and apoptosis, aiming to clarify mechanisms of age-related follicular dysplasia. Ninety women undergoing assisted reproductive technology were divided into reproductive-age (<35 years), advanced-age (35-41 years), and very advanced-age (≥42 years) groups. Clinical data and granulosa cell function were analyzed. PANX1 expression was detected in primary cells, while KGN cells were transfected with PANX1 plasmid or siRNA. Cell proliferation, apoptosis, and extracellular ATP levels were evaluated. With increasing age, oocyte yield, blastocyst formation, and pregnancy rates declined, granulosa cell proliferation decreased, apoptosis increased, and PANX1 expression was elevated. PANX1 overexpression inhibited proliferation and increased extracellular ATP, whereas knockdown enhanced proliferation without affecting apoptosis. PANX1 upregulation in aging granulosa cells mediates ATP efflux, depletes intracellular ATP, and suppresses proliferation, contributing to abnormal follicular development and reduced fertility.