Fosl2 Controls Gonadotropin-Dependent Folliculogenesis In Mice By Regulating Estradiol Synthesis

The follicle is the basic functional unit of the ovary and is composed mainly of oocytes and granulosa cells.Follicle development can be divided into gonadotropin-independent and gonadotropin-dependent phases.Follicle development can be divided into gonadotropin-independent and gonadotropin-dependent phases.Gonadotropin-dependent folliculogenesis includes expansion of the follicular antrum and follicular maturation.At this stage,the estrogen secreted by follicles has important physiological significance for regulating the estrus cycle and the maintenance of secondary sexual characteristics in female animals.The transcription factor Fos-like antigen 2(Fosl2)is a part of the transcription complex of activated protein 1(AP-1).Fosl2 plays an important role in regulating life activities such as growth,development and immune response.Fosl2 is highly expressed in follicular granulosa cells,but its function in follicles is still unclear.Fosl2 is highly expressed in follicular granulosa cells,but its function in follicular development is still unclear.In this study,we first explored its function at the cellular level,then performed functional validation at the tissue level using in vitro follicle culture technique,and finally used bioinformatics to predict the target genes of Fosl2 to initially explore the mechanism of action of Fosl2.The main findings are as follows:1.Firstly,the tissue expression pattern of Fosl2 in mice was detected at the mRNA level,and it was found that Fosl2 was expressed highest in the ovary.And the activation during follicle development was examined,and the results showed that Fosl2 expression in ovaries was induced by gonadotropins;2.Further at the cellular level,knockdown of Fosl2 expression in granulosa cells using RNA interference technology showed that knockdown of Fosl2 inhibited estrogen synthesis in granulosa cells,reduced cell proliferation rate and induced apoptosis in granulosa cells;3.At the tissue level,knocking down the expression of Fosl2 in follicles using RNA interference showed that knocking down Fosl2 significantly inhibited estrogen secretion,which inhibited gonadotropin-dependent folliculogenesis;4,The binding sites of Fosl2 to genes related to gonadotropin-dependent folliculogenesis were predicted by the JASPAR and GTRD databases,and Fosl2 regulation of estrogen synthesis may be achieved by regulating the expression of CYP11A1、STAR、FSHR and LHCGR genes.In summary,this study revealed that the transcription factor Fosl2 plays a critical function in follicular development.Fosl2 is induced by gonadotropins and regulates estradiol synthesis by regulating CYP11A1、STAR、FSHR and LHCGR genes expression in follicular granulosa cells,and is an essential transcription factor in gonadotropindependent folliculogenesis.