The Effect of Secretomes Derived from Umbilical Cord Mesenchymal Stem Cells on Embryo Development and Implantation Potential

Successful embryo implantation is a critical step in assisted reproductive technology and relies on the quality of blastocysts, uterine receptivity, and effective communication between the embryo and the endometrium. Implantation failure is a leading cause of pregnancy loss, and the low implantation success rate remains a major challenge for infertile patients undergoing assisted reproductive treatments. This study investigates the effects of secretomes derived from umbilical cord mesenchymal stem cells on embryo development and implantation.
Human trophoblast spheroids and murine embryos were used to assess the effects of UC-MSCs secretomes. An in vitro spheroid model was established to investigate an adhesion assay. Murine embryos obtained through superovulation were cultured and divided into a control and experimental groups treated with varying concentrations (2.5, 5, 10, and 50 µg/mL) of UC-MSCs secretomes. Blastocyst formation, hatching rates, and adhesion potential were evaluated. Gene expression analyses were conducted using qRT-PCR and RNA-seq to assess the expression of key implantation-related genes and pathways. Additionally, growth factor levels in culture media were analyzed.
Supplementation with UC-MSCs secretomes significantly enhanced trophoblast cell migration and spheroid adhesion, stimulated endometrial cell proliferation, and upregulated critical implantation-related genes, including LIF, LIFR, VEGFA, ITGB3, and ITGAV. In the murine model, while morulation rates remained unchanged, supplementation with UC-MSCs secretomes notably improved blastocyst formation, enhanced embryo quality through increased expression of pluripotency-associated genes, and elevated hatching rates. Significantly, it also increased embryo outgrowth and implantation rate following embryo transfer. Transcriptomic analysis revealed upregulation of genes linked to trophoblast differentiation, adhesion, and implantation. Activating cytokine-cytokine receptor interactions, extracellular matrix-receptor interactions, and the PI3K-Akt signaling pathway was identified as a key mechanism underlying implantation success. Growth factor analysis indicated elevated VEGF-A and PDGF-AA levels, further supporting enhanced embryo development and endometrial receptivity.
These findings underscore the therapeutic potential of UC-MSCs secretomes in supporting preimplantation embryos and improving maternal endometrial receptivity, offering promising avenues for enhancing implantation success rates in clinical settings.