Blastocyst-Secreted miR-519d-3p Modulated the Cell Viability, Apoptosis and Migration of Human Endometrial Stromal Cells by Targeting HIF1α.

Bidirectional embryo-endometrial communication is critical for embryo implantation. As a bio-sensor of embryos, the human endometrium is capable of mounting a response tailored to individual embryos, but how embryos signal their development potential remains an unresolved question. Emerging evidence showed that embryo-released miRNAs could mediate the interaction between the embryos and endometrium. In our previous study, miR-519d-3p was detected in the spent embryo culture medium with notably higher levels from implantation-failed blastocysts. To explore the role of miR-519d-3p at the maternal-fetal interface, human endometrial stromal cells (hESCs) were isolated and cultured in vitro. The miRNA uptake assay revealed that blastocyst-derived miR-519d-3p could be internalized by hESCs. miR-519d-3p overexpression significantly promoted cell apoptosis while suppressing cell viability and the migration of hESCs, as demonstrated by flow cytometry, CCK-8, and wound-healing assay. Furthermore, miR-519d-3p downregulated the expression of MMP-2, MMP-9, and VEGF-key proteins involved in hESC motility, uterine vascular permeability, and angiogenesis. HIF1α was a target of miR-519d-3p. With HIF1α overexpression, the biological effects of miR-519d-3p on hESCs were partially reversed. Taken together, blastocyst-secreted miR-519d-3p might contribute to the regulation of endometrial receptivity by targeting HIF1α, potentially offering a new perspective on embryo-maternal communication.