Inhibition of HIF-1 a Signaling in the Ovaries of Sprague-Dawley Rats with Polycystic Ovary Syndrome

摘要

Polycystic ovary syndrome (PCOS) is a major public health problem in reproductive-aged women worldwide, but the precise pathogenesis of PCOS remains unclear. Our previous study has clarified that hypoxia-inducible factor-1 alpha (HIF-la) mediated endthlin-2 (ET-2) signaling plays an important role in the ovulatory process in rats. Therefore, the present study used PCOS rat model to test the hypothesis that HIF-la signaling is inhibited in ovaries during PCOS fromation. By the changed of bodyweight, ovarian histology and ovarian weight, PCOS rat model was further confirmed. And then the present study examined the changes of ET-2 and HIF-la mRNA levels through real-time PCR finding the significant decrease of ET-2 mRNA level in PCOS rat ovaries was found, while HIF-la mRNA significantly increased. However, by western blot analysis, the present study found HIF-1 a protein expression was significantly decreased, which is consistent with ET-2 protein expression implying HIF-la-medated ET-2 signaling is vital during PCOS formation. Moreover, the result of HIF prolyl hyodroxylase activity analysis found the decrease of HIF-la protein may be caused through HIF protein degradation by the increased HIF prolyl hyodroxylase activity. Taken together, these results indicate that HIF-la signaling is inhibited in PCOS rat model through increase of HIF prolyl hyodroxylase activity suggesting HIF-la signaling plays an important role in the formation of PCOS. This HIF-la-mediaged ET-2 expression may be on of the important mechanisms regulating PCOS formation in mammalian ovaries in vivo.