Menstrual Blood-Derived Mesenchymal Stem Cells Improve Endometrial Receptivity in a Mouse Model of Embryonic Implantation Dysfunction.

Abstract

The decrease of endometrial receptivity leads to repeated implantation failure (RIF) during in vitro fertilization and embryo transfer. To explore the therapeutic potential of menstrual blood-derived mesenchymal stem cells (MenSCs) in addressing RIF, we established a murine model of embryonic implantation dysfunction using mifepristone. Subsequently, we administered MenSCs to these mice via tail vein injection and assessed their impact on the implantation and pregnancy rates of the affected mice. Furthermore, we conducted immunohistochemical staining on uterine tissues from these mice to examine the expression of endometrial receptivity markers, specifically vascular endothelial growth factor (VEGF)-A, HAND2, and HOXA10 following MenSCs transplantation. In parallel, we conducted in vitro studies to elucidate the molecular mechanisms of cell therapy by measuring the expression levels of VEGF-A, HAND2, and HOXA10 in endometrial stromal cells using real-time PCR and western blotting. In our mifepristone-induced mouse models, we observed a reduction in both pregnancy rates and implantation sites; however, these parameters were significantly improved after MenSCs transplantation. Similarly, the expression levels of VEGF-A, HAND2, and HOXA10 in the uterine tissues of the mifepristone group were diminished, but these levels were restored following MenSCs therapy. In vitro, after mifepristone treating, the expression of VEGF-A, HAND2, and HOXA10 decreased in endometrial stromal cells, but their expression increased after MenSCs coculture supernatant. In conclusion, these results demonstrated that MenSCs transplantation could increase endometrial receptivity by upregulating VEGF-A, HAND2, and HOXA10 expression. This study suggests MenSCs as a novel stem cell candidate in the treatment of RIF.