The use of mesenchymal stem cells derived from extracellular vesicles to increase bovine female reproductive potencial: therapeutic effects comprehension and profitability analysis

Abstract

In-vitro embryo production is an important tool for increasing productivity in females for genetic improvement of herds. Brazil is a world leader in this technology, and has begun exporting this knowledge in recent years. However, the follicular puncture (OPU - ovum pick-up) procedure used in collection of oocytes can cause important ovarian lesions, that are often irreversible. This complication limits embryo production, as well as the reproductive life-span of females, and as such is one of the main concerns related to the economic potential of this practice. In this context, this research group performed therapy with mesenchymal stem cells (MSC) in Nelore cows that had suffered ovarian lesions associated with the OPU procedure. The as-yet unpublished data showed that: 1) The intra-ovarian infusion of MSC is secure; 2) The use of MSC in ovaries with chronic lesions showed a positive effect on the production of oocytes and embryos, with improvement in all tested parameters; and 3) The application of MSC in cows with acute lesions promoted a significant increase in average oocyte production compared with control groups. With these experiments, we demonstrated the possibility of recuperation and increased productivity in bovine females with ovarian lesions caused by repeated OPU procedures. These results have an enormous potential economic impact in terms of in-vitro reproduction in Brazilian herds. In the present proposal, we plan to expand this study, by investigating the capacity of extracellular vesicles produced by MSC (MSC-EV) to produce similar therapeutic effects, with increased cost-benefit, and reduced logistical complexity compared to the use of MSC. The proposed approach will involve MSC culture in order to collect EV. The MSC-EV will be characterized in terms of size, concentration, protein markers, and RNA content. After characterization, the MSC-EV will be applied to bovine ovaries with acute lesions induced by the OPU procedure. The follicular environment will be examined with regard to content, and the collected oocytes will be analyzed with regard to number and quality. The rate of production and quality of embryos derived from these oocytes will also be examined. An analysis of the potential economic benefit will be carried out. Taken together, the results of this research project will contribute to understanding of the mechanisms of action of MSC-VE, and of their potential economic benefit for the bovinoculture industry, thus contributing to the overall productivity of this important Brazilian industry, as well as having potential future implications for human reproduction. (AU)