Extracellular vesicles derived from endometrial human mesenchymal stem cells improve IVF outcome in an aged murine model.

Abstract

Advanced age reduces the success of in vitro fertilization (IVF) being this effect partly mediated by an overproduction of reactive oxygen species (ROS) that trigger apoptosis. It has been demonstrated that extracellular vesicles derived from endometrial mesenchymal stem cells (EV-endMSCs) exert an antioxidant effect and can be used as IVF coadjutants. In this work, endMSCs were isolated from human menstrual blood (n=4) and characterized according to multipotentiality and surface marker expression prior EV-endMSCs isolation. Oocytes were obtained from 21 B6D2 mice (24weeks) and coincubated with sperm from young males (8-12weeks). Presumptive zygotes were incubated in the presence of 0, 10, 20, 40 or 80μg/ml of EV-endMSCs in KSOM medium. Blastocyst yield was evaluated, and 25 blastocysts per group were used for qPCR. Blastocyst rate was 29.4% in control; 45.2% for 10μg/ml, 62.9% for 20μg/ml, 55.5% for 40μg/ml and 53.8% in the 80μg/ml (n=124-130 oocytes) being all the increases significantly different when compared against control (p<0.05). The 20-80μg/ml treatments decreased the expression of glutathione peroxidase (Gpx1), and the 10-40μg/ml treatments reduced the expression of superoxide dismutase (Sod1; p<0.05) compared to control; Bax mRNA expression did not vary. Our results suggest that the increased developmental competence of the embryos could be partly mediated by the EV-endMSCs' ROS scavenger activity.