Human Embryo Exosomal miR-143-3p Impairs Decidualization by Targeting KRAS

Despite morphological selection, approximately 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-polymerase chain reaction 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 KRAS to inhibit its expression and suppress the downstream ERK/AKT 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 KRAS-ERK/AKT axis and may serve as a promising biomarker for the non-invasive assessment of embryo implantation potential.