The role of polarized macrophages in the activation of resolution pathways within human granulosa cells

Background: Inflammatory state within the ovaries can disrupt normal follicular dynamics, leading to reduced oocyte quality and infertility. Inflammatory genes expressed by human granulosa cells (hGCs), such as cyclooxygenase-2 (COX-2) and 5-, 12-, and 15-lipoxygenase (LOX), may be useful as potential effective biomarkers of oocyte competence with pregnancy outcome. How the production of inflammatory mediators generated by polarized macrophages might activate inflammatory pathways in hGCs remains unclear. Methods In this study, we evaluated how polarized M1 and M2 macrophages found in the ovaries affect the functions of hGCs isolated from women undergoing assisted reproductive technology. For this purpose, an indirect co-culture model was established between hGCs and conditioned media of M0, M1 and M2. We used real-time PCR and western blotting to detect the expression of COX-2 and 5-, 12-, and 15-LOX as biomarkers of oocyte competence. Results Our data showed that polarized M2 macrophages with anti-inflammatory characteristics were able to significantly increase the expression of COX-2 in hGCs. We also demonstrated that polarized M1 macrophages with pro-inflammatory characteristics were able to significantly increase the expression of 12-LOX in hGCs. However, there was no observed expression of 5-LOX and no significant alteration in the expression of 15-LOX in hGCs. Conclusions Our research indicated that the production of pro-resolving mediators by hGCs can, at least in part, reverse the physiological inflammation present in the ovaries, and the studied enzymes may be used in the future as biomarkers of oocyte competence.