Induction of aryl hydrocarbon receptor in granulosa cells by endoplasmic reticulum stress contributes to pathology of polycystic ovary syndrome

Abstract Recent studies have uncovered the critical role of aryl hydrocarbon receptor (AHR) in various diseases, including obesity and cancer progression, independent its previously identified as a for endocrine-disrupting chemicals (EDCs). We showed that endoplasmic reticulum (ER) stress, newly recognized local factor follicular microenvironment, is activated granulosa cells from patients with polycystic ovary syndrome (PCOS) mouse model disease. By affecting diverse functions cells, ER stress contributes to PCOS pathology. hypothesized expression AHR activation downstream signaling were upregulated by irrespective presence EDCs, thereby promoting pathogenesis. In this study, we found AHR, nuclear translocator (ARNT), target gene cytochrome P450 1B1 (CYP1B1) mice. examined CYP1B1 representative gene. ARNT human granulosa-lutein (GLCs), resulting an increase activity CYP1B1. Administration antagonist CH223191 mice restored estrous cycling decreased number atretic antral follicles, concomitant downregulation cells. Taken together, our findings indicate microenvironment pathology, represents novel therapeutic PCOS.