The Role Of P204 In Follicular Development In Mice With Premature Ovarian Failure Model

Interferon(IFN)-induced protein plays an important role in the function of interferon biological function.p204 is a member of the interferon-induced protein p200 family(IFI200)murine protein.It has been shown that the protein has the function of inhibiting cell proliferation,promoting cell differentiation and induction of exogenous double-stranded DNA invasion and other important role.In this study,we constructed models of premature ovarian failure using the whole-body p204 gene knockout(KO)and wild-type(WT)mice with the same genetic background by D-galactose injection.Eight weeks after modeling,the ovarian follicles and granulosa cells were observed by tissue sections.The levels of follicle-stimulating hormone(FSH),luteinizing hormone(HL),testosterone(T)and estradiol(E2)were measured by enzyme-linked immunosorbent assay.The expression levels of c-myc,Bcl-2,Bax,CYP17A1 and CYP19A1 in ovarian tissues were detected by real-time PCR.The expression and distribution of Bcl-2,CYP17al and CYP19A1 proteins in ovarian tissues were detected by immunohistochemistry.The results showed that the body weight and ovarian weight of KO mice decreased significantly(p<0.01)during the modeling process,while those of WT mice did not change significantly,indicating that p204 knockdown had a greater influence in mouse physiological function.According to the slicing and staining of ovarian tissue results,it was found that the ovarian follicles and corpus luteum were increased in KO mice,and the arrangement of granules was sparse,which indicated that p204 knockout had some influence on the development of ovarian follicles.The levels of testosterone(T),follicle stimulating hormone(FSH)and luteinizing hormone(LH)in KO mice were significantly increased(p<0.01).Indicating that p204 gene knockout after the mice to change the level of hormones,resulting in decreased follicular development,resulting in ovarian injury.The expression of bax and proto-oncogene c-myc in KO mice were significantly increased(p<0.01),the results showed that p204 knockout led to the apoptosis of ovarian granulosa cells,and accelerated premature ovarian failure.It was also found that the expression level of CYP17A1 which is sex hormone synthesis related genes in KO mice increased significantly(p<0.01).And the expression level of CYP19A1 gene decreased significantly(p<0.01).Indicating that p204 knockout changed the levels of sex hormones,especially androgen in mice,and led to follicular developmental disorders,thereby accelerating premature ovarian failure.Immunohistochemical results showed that deletion of p204 resulted in changes in the expression and distribution of Bcl-2,CYP17a1 and CYP19A1 proteins in the ovaries of mice.These results indicate that p204 may inhibit the formation of ovarian premature senescence by regulating the proliferation and apoptosis of granulosa cells in mouse ovarian follicular development.This study has important theoretical and clinical value for the role of p204 in the development of mouse POF follicles and pathogenesis and prevention of premature ovarian failure.The innovation points of this research are described as following.1)D-galactose injection was used to construct the model of premature ovarian failure in C57 strain p204 gene knockout mice.2)Lacking of p204 in mouse damaged to ovarian tissues and accelerated premature ovarian failure.