Abstract

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats.

Highlights

  • Polycystic ovary syndrome (PCOS) is a common endocrine disorder in their reproductive years, affecting 5%-10% of women worldwide [1]

  • Though two PCOS rats were clustered in the control group, they were in different branches

  • Principal component analysis (PCA) of DGGE fingerprints further confirmed the differences of gut microbiota between PCOS group and control group

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Summary

Introduction

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in their reproductive years, affecting 5%-10% of women worldwide [1]. The syndrome is characterized by the presence of at least two of the three classical features: hyperandrogenism, oligo-/anovulation and polycystic ovaries on pelvic ultrasound [2]. Women with PCOS, those with menstrual irregularities may have difficulties conceiving because of anovulation. PCOS patients frequently have metabolic disturbances with cardiovascular, type II diabetes, dyslipidemia, visceral obesity and endothelial dysfunction risk factors [3,4,5]. PCOS is not just a cosmetic and fertility problem and a major health problem that could shorten women’s life expectancy.

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