High-quality human preimplantation embryos actively influence endometrial stromal cell migration

The purpose of this paper is to study whether human preimplantation embryos regulate endometrial stromal cell (hESC) migration. Primary hESCs were isolated from fertile patients undergoing hysterectomy for benign conditions (uterine scar niche n = 3, dysmenorrhea n = 2; no hormonal treatment). Migration and proliferation assays were performed by culturing decidualized or non-decidualized hESCs in the presence of embryo conditioned medium (ECM) from high-quality embryos (fragmentation <= 20%) or from low-quality embryos (fragmentation > 20%) or in non-conditioned medium from the same dishes (control). ECM samples from 425 individually cultured human embryos were used in this study. ECM from high-quality embryos, i.e., with a low percentage of fragmentation, actively stimulated decidualized hESC migration (p < 0.001). This effect was consistent throughout embryonic development from cleavage stage embryos with 2-7 cells (high quality vs. control; p = 0.036), 8-18 cells (high quality vs. control; p < 0.001) to morulae (high quality vs. control; p = 0.003). Additionally, linear regression analysis showed that hESC migration was influenced by embryo quality (fragmentation, beta - 0.299; p = 0.025) and not developmental stage (cell number, beta 0.177; p = 0.176) or maternal age (beta - 0.036; p = 0.78). Opposite to decidualized hESCs, the migration response of non-decidualized hESCs was inhibited by ECM from high-quality embryos (p = 0.019). ECM from low-quality embryos, i.e., with a high percentage of fragmentation, did not cause an altered migration response in decidualized hESCs (p = 0.860) or non-decidualized hESCs (p = 0.986). Furthermore, ECM of both high- and low-quality human embryos did not influence the number of proliferating cells (p = 0.375) and the cell cycle time (p = 0.297) of non-decidualized or decidualized hESCs. This study reveals a mechanism by which high-quality human preimplantation embryos actively interact with the endometrium to increase their chances of successful implantation.