Improvement of the folliculogenesis by transplantation of bone marrow mesenchymal stromal cells in mice with induced polycystic ovary syndrome

Abstract

BackgroundMany studies have reported that inflammation and oxidative stress are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Bone marrow mesenchymal stromal cells (BM-MSCs) have anti-oxidant and anti-inflammation properties. In this study, we investigate the beneficial effect of stem cell therapy on folliculogenesis in mice with induced PCOS MethodsMouse model of PCOS was performed through daily injection of testosterone enanthate (1 mg/100 g/body weight subcutaneous (s.c).) for a period of 5 weeks. Naval Medical Research Institute (NMRI) mice (21 days old) were divided into three groups: control, PCOS and PCOS + BM-MSCs. BM-MSCs were labeled with Hoechst 33342 (0.5 µg/mL) and then injected into the mice (106/animal, via the tail vein) at 1 and 14 days after PCOS confirmation. Mice were humanely killed at 2 weeks after last transplantation. Ovarian stereological studies were done. Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), testosterone, interleukin (IL)-6 and tumor necrosis factor (TNF)-α serum levels were measured. The levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum were analyzed. Apoptotic index for ovarian follicles was assessed using Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). CD31 expression in ovarian vessels was assessed with the immunohistochemistry. ResultsThere was a significant increase in the total volume of ovary, cortex, number of antral follicles, volume of oocyte and zona pellucida thickness, and there was a significant decrease in the primary and preantral follicles number in the PCOS + BM-MSCs group compared with the PCOS group. There was a significant increase in the serum level of FSH and TAC and a significant decrease in the serum level of testosterone, LH, MDA and percentage of TUNEL-positive apoptotic cells in the PCOS + BM-MSCs group in comparison with the PCOS group. DiscussionBM-MSC transplantation improves folliculogenesis in mice with induced PCOS. BM-MSC therapy can be an operative treatment for PCOS via anti-inflammatory, anti-oxidant and anti-apoptotic properties.