Comparison and investigation on characteristics of polycystic ovary syndrome rat models induced by letrozole, testosterone propionate, and high-fat diets

Abstract

Abstract Background Due to the ethical limitations in human research, an ideal animal model is a critical resource for studying the etiology, pathophysiology, and long-term health outcomes of PCOS. However, no gold-standard rodent PCOS model has been achieved until now. The current study attempts to propose the ideal rat model for studies on polycystic ovary syndrome (PCOS). Results LE treatment induced hyperandrogenemia, further disrupting the estrous cycle, inducing polycystic ovary morphology, and impairing ovarian function. However, this effect could be restored within six weeks. Concurrently, LE enhanced excess fat storage, diminished adipocyte browning and energy expenditure, promoted hepatic steatosis, induced glucose intolerance, developed insulin resistance, affected the inflammation state, and compromised the intestinal barrier. HFD could amplify the effects of LE, particularly the metabolic disturbance. While the pituitary-ovarian axis was more efficiently and consistently affected by TP, which interrupted estrous cycle, overactivated primordial follicles, induced polycystic ovary morphology, altered hormonogenesis and expression of hormone receptors, suppressed follicle maturation, and influenced ovarian inflammation level. TP also altered the composition of intestinal microbiota and compromised the intestinal barrier. However, the effects on glucose, insulin, lipid, and energy metabolism were not as profound as LE, which can be supplemented by HFD. Conclusions LE is beneficial for studies on PCOS metabolic disturbances; LE + HFD is suitable for investigations on PCOS metabolic abnormalities and the gut-PCOS link. Whereas, T injection is appropriate for studying PCOS reproductive abnormalities; T + HFD treatment is the most comprehensive for PCOS reproductive abnormalities, metabolic disturbances, and the gut-PCOS link.