miRNAs secreted by human blastocyst could be potential gene expression regulators during implantation

Abstract

Background: Micro RNAs (miRNAs) are small non-coding RNAs known as essential regulators of cell-cell communication. Recent studies have revealed that miRNAs secrete by a blastocyst in culture mediums. We hypothesized that endometrial epithelial cells take up embryo-derived miRNAs and other soluble factors and regulate their receptivity-related genes expression. Methods and Results: Blastocyst culture mediums (BCM) were collected from the individually cultured embryos and, human endometrial epithelial cells (HEECs), were collected from healthy fertile volunteers. To evaluate the effect of BCM on the endometrial receptivity gene expression, HEECs were co-cultured with implanted BCM, non-implanted BCM, and a control culture medium. After determining altered gene expression in the HEECs, the miRNAs-related genes through bioinformatics databases were identified and evaluated in the BCM. Co-culture of primary HEECs with BCM significantly stimulated the expression levels of VEGFA, HBEGF, HOXA10, and LIF in the implanted group compared with non-implanted and control groups. The fold changes of miR‐195 significantly decreased in the implanted BCM group compared with the non-implanted BCM group. Also, we observed decreased fold changes of miR‐29b,145, and increased miR-223 in the implanted BCM group compared with the non-implanted ones. Conclusions: miRNAs' role as potential gene expression regulators during implantation. These molecules are secreted by human blastocyst, uptake by endometrial epithelial cells and cause a change in the endometrial function. We found that BCMs can be effective in implantation process by stimulating related receptivity gene expression, and BCM transfer with the embryo can be useful as an embryo implantation trigger.