Characteristics of polycystic ovary syndrome rat models induced by letrozole, testosterone propionate and high-fat diets

Abstract

Research question: What are the long-term effects of different models of polycystic ovary syndrome (PCOS), and which model could be used in future research?

Design: PCOS models induced by letrozole, letrozole plus high-fat diet (LE+HFD), testosterone propionate (TP) or testosterone propionate plus HFD (TP+HFD) were established in rats. Body weight, energy intake, blood glucose, sex hormone concentrations, lipid profiles and the oestrus cycle were observed. Histology of ovaries, large intestine and fat was displayed. Protein and mRNA levels relating to hormone synthesis, oocyte maturation, the gut barrier, lipid metabolism and inflammation were evaluated using western blotting, immunohistochemistry and PCR. The composition of the microbial community was measured using 16S RNA sequencing.

Results: Letrozole treatment induced hyperandrogenaemia, polycystic ovarian morphology, a disrupted oestrus cycle and impaired ovarian function, which could be restored within 42 days. Concurrently, letrozole disturbed glucose, fat, and energy metabolism, affected the inflammatory state and compromised intestinal homeostasis. HFD could amplify the disturbances in the metabolism and intestinal microenvironment, and the pituitary-ovarian axis was more efficiently and consistently affected by testosterone propionate. Testosterone propionate and TP+HFD treatment also disturbed the intestinal microenvironment. Although the metabolic effects of testosterone propionate were not as profound as those of letrozole, they were enhanced by HFD.

Conclusions: Letrozole is useful for studies on metabolic disturbances in PCOS, and LE+HFD treatment is suitable for investigations on PCOS metabolic abnormalities and the gut-PCOS link. Testosterone propionate injection is appropriate for studying reproductive abnormalities in PCOS, while TP+HFD treatment is the most comprehensive for studying PCOS reproductive abnormalities, metabolic disturbances and the gut-PCOS link.

Keywords: High-fat diet; Letrozole; Polycystic ovary syndrome; Rat models; Testosterone propionate.