Probiotics mitigates ovarian angiogenic disturbance in letrozole-induced PCOS

Abstract

BACKGROUND: Among metabolic/endocrine diseases affecting women in the reproductive years, polycystic ovarian syndrome (PCOS) is well documented as the leading cause of female infertility and several complications including dyslipidemia, cardiomorbidities, among others. Vascular endothelial growth factor (VEGF) is a proangiogenic marker which plays crucial roles in endothelial dysfunction, including ovarian dysfunction. Probiotics are gut microbiome that regulate metabolic health via epigenetic modulation of histone. Nevertheless, the present study was designed to investigate the beneficial effect of probiotics on aberrant ovarian angiogenesis in a PCOS rat model. MATERIALS AND METHODS: CFU (p.o) from probiotics for six weeks. RESULTS: The rats that received letrozole exhibited obesity, ovarian weight gain, hyperandrogenism, hypoestrogenism, and multiple ovarian cysts and demonstrated an increased level of anti-Mullerian hormone. Animals in this group also demonstrated ovarian triglyceride accumulation, inflammation, lipid peroxidation, elevated corticosterone as a parameter that show metabolic stress and elevated angiogenic factor (VEGF). Also, a decreased level of antioxidant defense (NrF2), and HIF-1a and a significant decrease in mitofusin 2 (Mfn2) was observed while histone deacetylase 2 (HDAC2) was significantly elevated when compared to the control group. Interestingly, treatment with probiotics significantly reversed these ovarian metabolic, biochemical and morphological changes. CONCLUSION: Collectively, the present result suggests that probiotics ameliorates aberrant ovarian angiogenesis with subsequent improvement of ovarian function in PCOS model. This beneficial effect of probiotics is accompanied by modulation of Mfn2 and suppression of HDAC2.