Abstract:Objective: To establish a mouse model of polycystic ovary syndrome (PCOS) with abnormal glucose and lipid metabolism by combining dihydrotestosterone (DHT) and high-fat diet. Methods: Sixteen 3-week-old clean grade female C57BL/6 mice were randomly divided into two groups for intervention for 6 weeks: the experimental group (8 mice) was treated with subcutaneous injection of DHT+high-fat diet, and the control group (8 mice) was treated with subcutaneous injection of organic solvent+ordinary diet. After the intervention, the estrous cycle, sex hormone level, ovarian pathology, body mass, blood glucose, blood lipid, subcutaneous and visceral fat depot of the two groups were compared to determine the success of the model. Results: After the intervention, the level of serum DHT in the experimental group was about 3 times higher than that in the control group (P=0.000) . After continuous observation for 14 days, the experimental group had no estrous cycle, while the control group had regular estrous cycle. The time of diestrus in the experimental group was significantly longer than that in the control group (P=0.001) , while the duration of proestrous (P=0.006) and estrous (P=0.000) was shorter than that in the control group. Under light microscope, the ovaries in the experimental group showed polycystic changes, the layers of granulosa cells decreased, the proliferation and thickness of theca cells increased, no corpus luteum was found, the number of small antral follicles (P=0.043) and large antral follicles (P=0.000) increased significantly, and the proportion of unhealthy follicles in small antral follicles (P=0.011) and large antral follicles (P=0.001) also increased significantly. The fasting blood glucose level (P=0.001) , area under the curve of IPGTT (P=0.012) and IPITT (P=0.007) in the experimental group were significantly larger than those in the control group. The weight increase of mice in the experimental group was significantly higher than that in the control group (P=0.005) , and the mass of retroperitoneal (P=0.007) , parametral (P=0.006) and inguinal (P=0.018) fat depot, serum triglyceride (P=0.009) and total cholesterol (P=0.000) were higher than those in the control group. Conclusion: The combination of DHT and high-fat diet can induce polycystic ovarian changes, estrous cycle changes and abnormal glucose and lipid metabolism in mice, which provides a mouse model for the experimental study of the pathogenesis of PCOS.
