Ovary Function Of Mice With Spontaneous Hyperuricemia

Hyperuricemia is closely related to gout,hypertension,diabetes mellitus,coronary heart disease,etc,and is correlated with the components of metabolic syndrome.Studies on the correlation between hyperuricemia and reproductive system function have been paid more attention in recent years,most of which focus on eclampsia,neonatal low weight and its pathogenesis.However,whether hyperuricemia is related to the functional or organic changes of reproductive organs remains to be further explored.In recent years,C57BL/6 mice with Uox-knockout(Uox-ko or ko)based on TALEN technology have been increasingly used in the study of hyperuricemia related diseases and pathogenesis.Due to the congenital deficiency of urate oxidase,serum uric acid level of Uox-ko mice increased spontaneously,providing a ideal animal model for the study of hyperuricemia-related diseases.In this study,female Uox-ko mice about 12 weeks old and their wild type(Uox-wt)control were selected to carry out a preliminary study on the ovarian endocrine and ovulation functions of mice by the following methods: Serum estradiol,follicle stimulating hormone and luteinizing hormone were determined by enzyme linked immunosorbent assay.The change of estrous cycle was monitored by vaginal exfoliated cell smear.Dissect mouse ovaries,measuring ovarian wet weight,serial section of the ovary,after HE staining to observe the structure of the organization and all levels of follicle number counting,The fibrous tissue structure was observed after reticular fiber staining and Massson staining.TUNEL assay was used to detect the apoptosis of oocytes and granulosa cells.Immunohistochemistry was used to analyze the expression of steroid-related enzymes,apoptosis and proliferation-related proteins,and estrogen receptor proteins in the ovarian microenvironment.The results showed that the serum estradiol level and follicle stimulating hormone level of Uox-ko group mice were significantly higher than that of Uox-wt group,and there was no significant difference in the number of days of estrus cycle between the two groups,but the estrus duration of ko group was significantly higher than that of wt group.TUNEL results showed that the two groups of mice follicular apoptosis granulosa cells significantly different,but ko group of ovarian corpus luteum apoptosis cells more.Immunohistochemical results showed that there was no significant difference in the expression of casp-3,a protein related to apoptosis,between the two groups.The number of casp-3 positive cells in luteal cells was significantly higher than that in wt group,while the expression of PCNA,a proliferationrelated protein,was lower than that in wt group.In the granulosa cells,the key enzyme of the estrogen synthesis step,STAR,was more highly expressed in the ko group,while the key protein CYP19 related to estrogen transformation was not significantly different.The estrogen receptor was more highly expressed in the follicular tissue of the ko group and was rarely expressed in the corpus luteum.This study found that the ruled out the premise of the influence of environmental factors and other genetic background.Uox-ko gene knockout mice can affect serum estradiol levels and follicle-stimulating hormone levels,its action can be by adjusting the STAR expression of key enzymes of estradiol synthesis,at the same time,the positive feedback regulation of mouse estrogen may increase the release of gonadotropin.The apoptosis rate of luteal cells in Uox-ko mice was higher than that in the control group,but the apoptosis rate of granulosa cells was not obvious.It was speculated that the possible reason for this phenomenon was that uric acid higher than the physiological concentration played a pro-apoptotic effect,and granulosa cells expressed more estrogen receptors,thus under the apoptosis effect of antagonism of estradiol,granulosa cell apoptosis was not significant.In this study,it was found that mice with Uox knockout may secrete higher levels of estrogen,accompanied by increased apoptosis of ovarian cell tissue.This double-sided effect may be caused by higher levels of uric acid,but the specific mechanism needs to be further studied to deepen our understanding of hyperuricemia.