Therapeutic potential of sodium selenite in letrozole induced polycystic ovary syndrome rat model: Targeting mitochondrial approach (selenium in PCOS)

Abstract

Polycystic ovary syndrome (PCOS) is the most common endorinopathy in fertile women with heterogeneous reproductive and metabolic phenotypes and unknown etiology. This study was undertaken to investigate the beneficial effect of selenium in management of letrozole induced PCOS and its role in modulating mitochondrial dynamics, and its associated signals. Twenty four adult female rats were enrolled and randomly divided into four equal groups; control group received 0.5% w/v carboxymethyl cellulose (CMC); PCOS group received letrozole (1 mg/kg, daily) in 0.5% CMC for 21 days. From day 22 to day 36, after letrozole PCOS induction, the (PCOS +Metformin) group received metformin (2 mg/kg, daily) while (PCOS + sodium selenite) group received sodium selenite (0.1 mg/kg, daily). All doses were given via oral gavage. At the study end, serum hormone levels, lipid profile and HOMA-IR were assessed. Ovaries were dissected, used for histopathological evaluation, immunohistochemical detection of B-cell lymphoma-2 (Bcl-2), and its associated X protein (Bax) expression, measurement of redox status, mitochondrial dynamics markers and citrate synthase (CS) activity. Furthermore Mitofusins 2 (Mfn2) and dynamin related protein 1 (Drp1) mRNA expression was assessed by real time PCR. Selenium treatment of PCOS rats succeeded, comparable to metformin, to greatly improve the PCOS associated endocrine and metabolic phenotypes and histopathological changes, mostly through modulating mitochondrial dynamics, anti-apoptotic action, alleviating oxidative stress and mitochondrial dysfunction. So, selenium could provide a novel therapeutic strategy for PCOS.