Introduction: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility affecting over 5% of the female population. PCOS is characterized by aberrant early follicle development in which hyperandrogenism is thought to play a key role. However, the molecular mechanisms of androgen action within the ovary remain largely unknown. Recent evidence suggests androgens may be acting, in part, through modulation of growth factor signalling. We have recently shown that members of the epidermal growth factor (EGF) family play an important role in promoting preantral follicle development in the mouse. The aim of this study was to investigate androgenEGF interaction within preantral follicles.
Materials and methods: Preantral follicles obtained from PND 15 mouse ovaries (C57BL/6) were isolated and cultured in the presence of EGF (10 ng/ml), dihydrotestosterone (DHT) (10 nM) with or without the EGF receptor (EGFR) inhibitor AG1478 (10 μM). Follicle growth was monitored over 72 h, with samples processed for qPCR and immunohistochemistry at 24 and 72 h.
Results and discussion: EGF treatment significantly increased follicle growth from 24 h onwards (P<0.001). DHT increased preantral follicle growth from 48 h (P<0.0001), fitting with the PCOS phenotype. Combined incubation with EGF and DHT resulted in elevated growth above that of individual treatments (P<0.05), indicating an additive effect. The addition of AG1478, a specific EGFR tyrosine kinase inhibitor, not only reversed EGF regulated follicle growth but also attenuated the effect of DHT on growth at 48 h (P<0.001), suggesting that the effects of DHT on follicle growth are mediated, at least in part, through the EGFR.
02 - 04 Sep 2014
World Congress of Reproductive Biology