Recherche de biomarqueurs par approche métabolomique et cytokinique en assistance médicale à la procréation

During the course of our research, we sought to analyze the pathophysiological mechanisms incriminated in ovarian aging and endometriosis, by studying the possible impact of these conditions on the oocyte micro-environment. We have identified specific signatures for these pathologies in the follicular fluid, andin some cases, potential biomarkers. In cases of infertility secondary to isolated endometriosis, we did not find any alteration of the metabolic profile of the follicular fluid. The absence of an alteration in the oocyte micro-environment in women with endometriosis suggests that there is no impact of the disease on the oocyte quality. However, in cases of severe endometriosis, cytokine analysis showed that, in some patients, there is a different expression of MCP1 in the follicular fluid. We also found a modification of the oocyte micro-environment in severe endometriosis, associated with high levels of MCP1. In cases of low ovarian reserve, we found decreased levels of unsaturated plasmalogens and an increase in the methyl-transferase activity, suggesting oxidative stress in the follicular fluid. Moreover, the analysis of the cytokines profile showed a significant decrease in PDGF-BB concentrations in patients with low ovarian reserve. The alteration of the metabolic pathway simplicating PDGF-BB could negatively impact folliculogenesis and the antioxidant defense mechanisms, and could therefore be linked to the infertility seen in patients with low ovarian reserve. Finally, our future research will look to identify eventual biomarkers and to improve our understanding of the pathophysiologic mechanisms involved in recurrent pregnancy losses and recurrent implantation failures following in vitro fertilization treatment.