Mesenchymal Stem Cell Transplantation as a Therapeutic Strategy to Preserve Testicular Integrity and Counteract Microgravity-Induced Male Infertility

Background: Prolonged immobility and exposure to microgravity during spaceflight negatively affect male reproductive organs. Various interventional strategies have been employed to mitigate testicular pathology in immobile and/or physically inactive men. However, an effective therapy remains elusive. The experimental rodent model of simulated microgravity (SM), is widely used to study the pathogenesis of male infertility during prolonged bed rest and spaceflight. Methods: The study was conducted using four-month-old, male C57BL/6J mice. The mice were divided into three groups: ground controls (GC), hindlimb unloaded (HU) treated with vehicle mice (SM-V), and HU mice that underwent MSC transplantation (SM-MSCs) (n = 6 mice/group). Aim: We investigated the therapeutic potential of intratesticular transplantation of MSCs in a mouse model of SM. Results and Conclusions: We examined testicular histology and global transcriptome to dissect the effects of HU and/or MSCs on mouse testes. Testicular histology revealed that treatment with MSCs significantly increased the tubular diameter and epithelial height in the testes of mice (p <0.05). Transcriptomic studies revealed significant effects of MSC treatment in reversing the molecular pathways that are debilitated by SM in testicular tissues. This study demonstrates the potential of MSC transplants to reverse the debilitating effects of SM on murine testes, and highlights a promising area of research for cell-based therapies in the context of planned manned space missions. Therefore, we conclude that an MSC transplant is a promising treatment for reversing the disruption of testicular microarchitecture and molecular pathways associated with HU.