Role of OCT4 in the Regulation of FSH-Induced Granulosa Cells Growth in Female Mice

Dai Heng,Qiaozhi Wang,Cheng Zhang,Wenbo Liu,Ye Tian,Xiaoshu Ma,Xuechun Weng,Kaili Xu,Xusong Hu

doi:10.3389/fendo.2019.00915

Abstract

As a member of the POU (Pit-Oct-Unc) transcription factor family, OCT4 (Octamer-binding transcription factor 4) is associated with the cellular proliferative. However, the roles of OCT4 in regulating the transition from preantral follicle to early antral follicle are still remains unclear. To evaluate the effect of OCT4 on cellular development in ovary, mice were injected with eCG in vivo or granulosa cells were co-cultured with FSH in vitro. The results showed that eCG up-regulated ovarian OCT4 expression. Meanwhile, OCT4 expression in granulosa cells was also up-regulated by FSH, and knockdown of OCT4 by siRNA significantly decreased FSH-induced cellular viability. Moreover, gonadotropin increased p-GSK3β (Glycogen synthase kinase 3-beta) level, β-catenin expression and its translocation to nuclear in ovarian cells. In addition, the inhibition of GSK3β activity by CT99021 significantly increased the expression of β-catenin and OCT4 in granulosa cells. And knockdown β-catenin by siRNA dramatically abolished FSH-induced OCT4 expression and cellular development. Furthermore, FSH-induced the phosphorylation of GSK3β, expression of β-catenin and OCT4, and translocation of β-catenin were mediated by the PI3K/Akt pathway. Taken together, the present study demonstrates that FSH regulated OCT4 expression via GSK3β/β-catenin pathway, which was mediated by the PI3K/Akt pathway. And these regulations are involved in ovarian cell development.

Highlights

Mammalian ovarian follicular development is a highly selective process that is complex and accompanied by cell proliferation, differentiation, or apoptosis [1,2,3,4,5,6]
The present study demonstrates that follicle-stimulating hormone (FSH) regulated Octamer-binding transcription factor 4 (OCT4) expression via glycogen synthase kinase 3-beta gene (GSK3β)/β-catenin pathway, which was mediated by the phosphatidylinositol 3-kinase (PI3K)/Akt pathway
We have demonstrated that FSH-induced granulosa cells development through up-regulating OCT4 expression in mice

Summary

Introduction

Mammalian ovarian follicular development is a highly selective process that is complex and accompanied by cell proliferation, differentiation, or apoptosis [1,2,3,4,5,6]. OCT4 can promote ovarian mesenchymal cell proliferation and increase the potency to promote oogenesis, and regulates the development of membrane cells and granulosa cells [15]. It has been reported that OCT4 is detected in oocyte and granulosa cell of growing follicles, and plays important roles in oocyte growth and FSH Regulates OCT4 Expression meiosis [14, 16, 17]. The precise roles and mechanisms of OCT4 during the early follicular development are not known

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Results

Conclusion