Increased Trimethylamine N-oxide Contributes to Metabolic dysfunction in a Rat Model of PCOS and Decreases Mitochondrial function

Abstract Polycystic ovarian syndrome (PCOS) is a common endocrine disease in adolescents and women of childbearing age, also a common cause of female infertility. In recent years, studies have found that the occurrence of PCOS is related to changes in the intestinal flora. Trimethylamine N-oxide (TMAO) is an organic compound produced by intestinal microorganisms. However, the relationship between TMAO and PCOS remain mostly unexplored. The effects of TMAO on PCOS were assessed in vitro and in vivo. In a PCOS rat model, plasma TMAO, hormone and PI3K signaling levels were examined. In the process of in vitro maturation (IVM), immunofluorescence and confocal microscopy were used to detect the influence of adding different TMAO concentrations to the culture medium on oocytes. The fasting insulin (FINS), HOMA-IR, luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) and plasma TMAO levels of the PCOS rat group were significantly higher than those of the control group. Treatment with the TMAO inhibitor 3,3-dimethyl-1-butanol (DMB) alleviated metabolic disorder in PCOS rats. In PCOS rats, DMB improved the PI3K/Akt-related signaling pathway compared to no treatment. In IVM, the mitochondria of oocytes in the TMAO groups were aggregated and distributed, and mitochondrial membrane potential and ATP content were decreased. Apoptosis was more severe in the TMAO group than in the control group. TMAO worsened metabolic dysfunction in a rat model of PCOS and decreased the mitochondrial function of oocytes in the process of IVM.