Autologous mitochondria transport via transzonal filopodia rejuvenates aged oocytes by UC-MSCs derived granulosa cells-oocyte aggregation

Abstract

Mitochondria transfer can rescue oocyte aging-related infertility. However, heterologous techniques are suspended due to heteroplasmy. Regarding autologous approaches, the donor source and manipulating procedures require further optimization. Here we propose a strategy using umbilical cord mesenchymal stem cells (UC-MSCs) as mitochondria donor cells and employing intercellular mitochondria transport as the transfer method. We cryopreserved UC-MSCs of the female pup. When the female aged, its UC-MSCs were induced into granulosa cells (iGCs). The zona-weakened GV oocytes were aggregated with autologous iGCs into iGC-oocyte complexes. After cultivation in GDF9-containing media, mitochondria migrated from iGCs into the GV oocyte via transzonal filopodia. The maturation rate, quality, and developmental potential of these oocytes were substantially increased. Furthermore, the birth rate after embryo transfer has been improved. This approach utilized noninvasive procedures to collect mitochondria donor cells and optimized mitochondria transfer manipulations, so may represent a promising advance towards the improvement of aging-related infertility.