HB-EGF was abundantly noted in follicular fluid of PCOS patients, where it might bind to EGFR and induce the GCs production of more estrogen through cAMP-PKA-JNK/ERK-Ca2+-FOXO1 pathway, resulting in mitochondrial dysfunction and GCs apoptosis (Figure 8). The gene discussed is FOXO1; the disease is polycystic ovary syndrome.