Expression Of Puma In Follicular Granulosa Cell Via JNK-dependent FoxO1 Activation Induced By Oxidative Stress

A lot of researches have demonstrated that granulosa cell apoptosis is a critical factor causing follicular atresia,but the molecular mechanisms of granulosa cells apoptosis are still not identified completely.In our previous study,FoxO1 was shown to be critical in oxidative stress-induced granulosa cell apoptosis.However,the regulatory mechanisms of FoxO1 are still unclear.Our aim is to find out the cell signaling pathways of granulosa cell apoptosis mediated by FoxO1.In this study,we found that c-Jun N-terminal kinase(JNK)could be activated under the oxidative stress condition,while could further activate the expression of the phosphorylated transcription factors FoxO1 by promoting its import in the nucleus.Moreover,we found that p53-upregulated modulator of apoptosis(Puma),a member of BH3-only Bcl-2 subfamily protein,was a downstream regulatory factor of FoxO1,which can facilitate Puma expression at protein and mRNA level.Oxidative stress can also induce the increase of Puma expression can be regulated by JNK.In conclusion,JNK-dependent FoxOl activation induced by oxidative stress can increase Puma expression in follicular granulosa cell.This study improved the molecular mechanism of follicular atresia on exploring the regulatory mechanism of ovarian granulosa cell apoptosis induced by oxidative stress.It provided a basis for research to improve the reproductive capacity of dams and treatment of human reproductive disorders.