Human embryo exosomal miR-143-3p impairs decidualization by targeting KRAS

In brief: Aberrant embryo-maternal cross-talk is a potential cause of in vitro fertilization failure. This study reveals that embryo-derived exosomes may carry specific microRNAs that impair endometrial receptivity. Abstract: Despite morphological selection, ∼40% of transferable embryos fail to implant during in vitro fertilization, potentially due to aberrant embryo-maternal cross-talk. Pre-implantation embryos release extracellular vesicles into their microenvironment, which may participate in embryo-maternal communication. This study investigated the microRNA expression profiles of extracellular vesicles derived from pre-implantation human embryos and analyzed their functional effects on the decidualization of endometrial stromal cells. Extracellular vesicles were isolated from the spent culture media of day 5 blastocysts associated with either successful clinical pregnancy or implantation failure. Sequencing and quantitative reverse transcription-PCR were performed to identify and validate differentially expressed microRNAs. Functional effects were assessed by measuring decidualization markers, while regulatory mechanisms were evaluated via western blotting. We found that miR-143-3p expression was significantly upregulated in blastocyst-derived extracellular vesicles from the implantation failure group. Mechanistically, miR-143-3p hinders the decidualization process of endometrial stromal cells by targeting Kirsten rat sarcoma viral oncogene homolog to inhibit its expression and suppress the downstream extracellular regulated protein kinase/protein kinase B signaling pathway. This study provides the first characterization of microRNA expression profiles in extracellular vesicles derived from pre-implantation embryos of in vitro fertilization patients, revealing a novel mechanism in embryo-maternal cross-talk. Our findings suggest that exosomal miR-143-3p acts as a negative regulator of decidualization via the Kirsten rat sarcoma viral oncogene homolog-extracellular regulated protein kinase/protein kinase B axis and may serve as a promising biomarker for the non-invasive assessment of embryo implantation potential.