GPX3 Overexpression in Cumulus Cells Entails a Poor Prognosis for Uterine Implantation of Morphotype A Embryos

SIMPLE SUMMARY: Despite the fact that human assisted reproduction has undergone extensive development with positive effects on pregnancy, the rates of success are still low. The morphokinetic score of preimplanted embryos is the common routine procedure for ART centres as a reliable predictor of implantation. However, the morphological quality of the embryo is not sufficient to fully ensure implantation success. Therefore, the identification of good predictors of implantation is mandatory to optimise assisted reproduction technology (ART). In this regard, the transcriptome study of the cumulus cells (CCs) is a non-invasive procedure that reflexes the physiological state of oocytes, given the molecular crosstalk between both types of cells. The present study shows a significant down-regulation of the GPX3 gene expression in the CCs isolated from oocytes in pregnant women compared to CCs from non-pregnant women who underwent assisted reproduction. Interestingly, CCs of the highest quality morphotype (A embryos), which achieved implantation success, expressed significantly lower levels of GPX3 expression compared to the embryo morphotype A with implantation failure. Therefore, our observations point to the expression of the GPX3 gene as a potential prognostic marker of bad implantation. ABSTRACT: Morphological embryo quality is an accurate prognostic tool for the success of assisted reproduction implantation, although complete certainty cannot be guaranteed. The transcriptome of the cumulus cells could be monitored as a faithful reflex of the physiological state of the oocytes, given the molecular crosstalk between both types of cells. Here, we compare the expression of specific genes related to oocyte competence, such as hyaluronic acid synthase 2 (HAS2), cell division control protein 42 (CDC42), connexin 43 (CX43), and glutathione peroxidase 3 (GPX3), in cumulus cells from implanted versus non-implanted embryos in 25 women, using RT-qPCR. After embryo transfer, two cohorts were differentiated: the pregnant group (women with the implantation of 100% of embryos transferred) versus the non-pregnant group (with an absence of embryo implantation), aiming to compare the possible differential expression of the selected genes in the cumulus cells of embryos from each group. HAS2, CDC42 and CX43 did not reveal differential expression between the two cohorts. However, GPX3 showed significantly reduced expression in the cumulus belonging to the pregnant group. Interestingly, even cumulus cells belonging only to morphotype A embryos showed a significantly lower expression of GPX3 in the pregnancy group. GPX3 overexpression in cumulus cells could be a poor prognostic indicator of implantation, discriminating beyond the capacity of the morphokinetic score. Unveiling the cumulus transcriptome could improve successful implantation in assisted reproduction treatments.