Regulatory effects of progesterone on HIF-1alpha and ET-2 expression during gonadotropin-induced superovulation in SD rats

摘要

Ovulation is a complex physiological process in the mammalian ovary, we currently reported that hypoxia-inducible factor (HIF)-1a plays a critical role in the regulation of ovulation in the Sprague-Dawley rats primed by gonadotropins. The present study was designed to test the regulatory effects of the increased progesterone (P4) on HIF-la and endothelin-2 (ET-2) expression during gonadotropin-induced superovulation in Sprague-Dawley rats. A significant increase of HIF-1a and ET-2 mRNA levels was found in the ovaries from the rats treated with gonadotrophins, which is consistent with the change of serum P4 concentration. Interestingly, this ET-2 mRNA increase was blocked by the specific progesterone receptor (PR) inhibitor CDB and then reversed by the HIF-la activator cobalt chloride (CoCl_2) cotreatment, not HIF-la small molecular inhibitor echinomycin (Ech). The result of oocyte numbers released further indicated this increased P4 may play an important role in HIF-1a/ET-2 expression and following ovulation. Together, these results suggest this induced ET-2 expression by the increased P4 contributes to gonadotropin-induced superovulation through PR-mediated HIF-la signaling pathway in the Sprague-Dawley rats. To our knowledge this will provide a new insight into the important mechanism of HIF-1a/ET-2-dependent ovulation in the mammalian ovary.