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

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.

Keywords: GPX3; cumulus cells; implantation; infertility; oocyte competence; transcriptome.

Figure 1

Expression of genes involved in the development of oocytes in cumulus cells. Relative expression of HAS2, CDC42, CX43, and GPX3 in cumulus cells retrieved from follicles of the pregnant group (n = 17) compared to the non-pregnant group (n = 55; dashed line). Data represent the mean ± SEM. * p < 0.001 compared to the non-pregnant group.

Figure 2

(A) Embryo grading. Data represent the % of each grade of embryo quality achieved in both groups for this study. (B) Relative expression of the GPX3 mRNA in cumulus cells retrieved from follicles whose embryo achieved grade A quality. Data represent the mean of the calculated values compared to cumulus cells retrieved from follicles of the pregnant group (n = 17), with the 2^−ΔΔCt method, and the standard error of the mean of each group (n = 55). * p = 0.0115 compared to the non-pregnant group.