Influence of hyperuricemia on the reproductive function of female rats and its mechanism

Abstract

Objective To investigate the influence of hyperuricemia (HUA) on the reproductive function of female rats and its mechanism. Methods A total of 18 female Wistar rats were randomly divided into HUA group, HUA recovery group (HR group), and control group (N group), with 6 rats in each group. The rats in the HUA group and the HR group were given intragastric administration of 50 mg/kg uric acid and intraperitoneal injection of 250 mg/kg oteracil potassium every day, and since week 9, the rats in the HR group were given an equal volume of normal saline by gavage and intraperitoneal injection, while the treatment remained unchanged for those in the HUA group, for another 7 weeks; the rats in the N group were given an equal vo-lume of normal saline by gavage and intraperitoneal injection for 16 weeks. At week 16, body weight, uterine mass, and ovarian mass were measured for all three groups, and uterine and ovarian coefficients were calculated; hematoxylin-eosin staining was used to observe the pathological changes of the uterus and ovarian tissue; enzyme-linked immunosorbent assay was used to measure the serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2); the vaginal exfoliation cell smear method was used to observe the estrous cycle of rats; colorimetry was used to measure the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in uterine tissue of the three groups; immunofluorescence assay was used to measure the fluorescence intensity of tumor necrosis factor-α (TNF-α) in uterine tissue of the three groups. Results Compared with the N group, the HUA group had significant reductions in uterine coefficient, number of follicles, endometrial thickness, and estrous interval, a significant increase in the serum level of FSH, significant reductions in the levels of SOD and GSH in uterine tissue, and a significant increase in the content of MDA (F=7.80-111.40,t=3.95-12.37,P<0.05), as well as an increase in the fluorescence intensity of TNF-α in uterine tissue. Compared with the HUA group, the HR group had significant increases in the number of follicles, endometrial thickness, the serum level of FSH, and the levels of SOD and GSH in uterine tissue and a significant reduction in the level of MDA (t=3.40-11.56,P<0.05), as well as a reduction in the fluorescence intensity of TNF-α in uterine tissue. Conclusion HUA can cause the decline of reproductive function in female rats, which may be associated with the increase in the serum level of uric acid, the disorder of sex hormone secretion, the increase in the level of oxidative stress, and the induction of inflammatory response.

Keywords

• hyperuricemia|estrus|gonadal steroid hormones|cytokines|inflammation|oxidative stress|females|rats, wistar