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

Abstract

Research QuestionWhat are the long-term effects of different models of polycystic ovary syndrome (PCOS), and which model could be used in future research? DesignPCOS models induced by letrozole (LE), LE and high-fat diets (HFD), testosterone propionate (TP), or TP and HFD were established respectively. Body weight, energy intake, blood glucose, sex hormone levels, lipid profiles, and estrous cycle were observed. Histology of ovaries, large intestine, and fat were displayed by Hematoxylin-eosin or Oil red O staining. The protein and mRNA levels of the hormone synthesis, oocyte maturation, gut barrier, lipid metabolism, and inflammation were evaluated using western blot, immunohistochemistry, and polymerase chain reaction. Microbial community composition was measured by 16S RNA sequencing. ResultsLE treatment induced hyperandrogenemia, polycystic ovary morphology, disrupted estrous cycle, and impaired ovarian function. However, these effects could be restored within 42 days. Concurrently, LE enhanced excess fat storage, diminished adipocyte browning and energy expenditure, developed insulin resistance, affected the inflammation state, and compromised the intestinal barrier. HFD could amplify the metabolic disturbance. While the pituitary-ovarian axis was more efficiently and consistently affected by TP. TP also disturbed intestinal microenvironment. However, the effects on metabolism were not as profound as LE, which can be supplemented by HFD. ConclusionsLE 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 studying PCOS reproductive abnormalities, metabolic disturbances, and the gut-PCOS link.