Endocrine Abstracts

Background: Polycystic ovarian syndrome (PCOS) is critically characterized with metabolic and endocrine dysfunctions, precipitating metabolic syndrome and infertility in reproductive aged women. Adipose tissue dysfunction has been implicated in the pathogenesis of metabolic syndrome, including in PCOS individuals. Probiotics are healthy bacteria in the gut that regulate metabolic health. However, the impact of probiotics on adipose-driven metabolic syndrome has not been reported. The present study therefore hypothesized that probiotics would attenuates metabolic disturbance in experimental PCOS rat model, probably by modulation of HIF-1α.

Materials and methods: Eight-week-old female Wistar rats were randomly allotted into four groups (n = 5). Administration of letrozole (1 mg/kg p.o) for 21 days induced PCOS, thereafter the animals were treated with 2x10⁷ CFU (p. o) of probiotics for six weeks.

Key findings: Letrozole-induced PCOS rats were characterized with elevated circulating testosterone, and multiple ovarian cysts. In addition, rats with PCOS developed increased body weight, which was also accompanied with insulin resistance, hyperinsulinemia, and increased leptin, and decreased adiponectin, adipose TG, as well as elevated adipose lipase. Inflammatory markers (NF-kB, TNF-α) and macrophage inhibitory factor were elevated, while antioxidant defense (GSH) was depleted in PCOS animals. A significant increase in adipose TGF-β1, caspase-6 and HDAC2 levels was observed in PCOS rats when compared with the control. Immunohistochemical evaluation of adipose tissue also showed severe expression of NLRP3 in PCOS rats and these changes were accompanied by decreased expression of HIF-1α. However, treatment with probiotics reversed these aberrant systemic and adipose tissue change in PCOS model.

Significance: The present results suggest the therapeutic benefit of probiotics, against adipocyte dysfunction in PCOS rat model, through modulation of HIF-1α/MIF-dependent pathway.

Keywords: Adipose; HDAC2; HIF-1α; Inflammation; PCOS; Probiotics.