Runan Hu , Yanjing Huang , Zhuo Liu , Haoxu Dong , Wenwen Ma , Kunkun Song , Xiaohu Xu , Xiao Wu , Yuli Geng , Fan Li , Mingmin Zhang , Yufan Song
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引用次数: 0
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.
期刊介绍:
Reproductive BioMedicine Online covers the formation, growth and differentiation of the human embryo. It is intended to bring to public attention new research on biological and clinical research on human reproduction and the human embryo including relevant studies on animals. It is published by a group of scientists and clinicians working in these fields of study. Its audience comprises researchers, clinicians, practitioners, academics and patients.
Context:
The period of human embryonic growth covered is between the formation of the primordial germ cells in the fetus until mid-pregnancy. High quality research on lower animals is included if it helps to clarify the human situation. Studies progressing to birth and later are published if they have a direct bearing on events in the earlier stages of pregnancy.