HB-EGF enhanced the apoptosis rate of GCs, which might facilitate the abnormalities of folliculogenesis and account for anovulation and aberrant steroidogenesis in PCOS 51,52, and promoted the cleavage and activity of CASP3 that were the principal executor of apoptosis 49, while blockage of mPTP opening by ER-000444793 attenuated the induction of HB-EGF on GCs apoptosis, implying that HB-EGF induced apoptosis via the mitochondria-dependent pathway. This evidence concerns the gene HBEGF and polycystic ovary syndrome.