The present study revealed that HB-EGF was abundant in follicular fluid of PCOS patients, where it might induce the hypersecretion of estrogen and bring about mitochondrial dysfunction and apoptosis of GCs through cAMP-PKA-JNK/ERK-Ca2+-FOXO1 pathway dependent on EGFR. Here, MAPK8 is linked to polycystic ovary syndrome.