Expression Levels of PPAR gamma and CYP-19 in Polycystic Ovarian Syndrome Primary Granulosa Cells: Influence of omega-3 Fatty Acid

Background: The omega-3 fatty acid (omega-3 fatty acid) such as eicosapentaenoic acid (EPA) is currently used in the clinic as a nutritional supplement in the treatment of polycystic ovarian syndrome (PCOS). The present study was designed to investigate the effect of EPA on the expression levels of peroxisome proliferator-activated receptor gamma (PPAR gamma) and cytochrome P450 aromatase (encoded by the CYP-19) in primary cultured granulosa cells (GC) from patients undergoing in vitro fertilization (IVF), and also to compare these effects with those in GC of PCOS patients. Materials and Methods: In this experimental study, human GC were isolated, primary cultured in vitro, exposed to a range of concentrations of the EPA and investigated with respect to gene expression levels of PPAR gamma and CYP-19 using real time-polymerase chain reaction (PCR). The participants (n=30) were the patients admitted to the IVF Center in February-March 2013 at Alzahra Hospital, Tabriz, Iran, who were divided into two groups as PCOS (n=15) and non-PCOS (n=15) women (controls). Results: All doses of the EPA significantly induced PPAR gamma mRNA gene expression level as compared to the control recombinant follicle stimulating hormone (rFSH) alone condition. High doses of EPA in the presence of rFSH produced a stimulatory effect on expression level of PPAR gamma (2.15-fold, P=0.001) and a suppressive effect (0.56-fold, P=0.01) on the expression level of CYP-19, only in the PCOS GC. Conclusion: EPA and FSH signaling pathway affect differentially on the gene expression levels of PPAR gamma and CYP-19 in PCOS GC. Altered FSH-induced PPAR gamma activity in PCOS GC may modulate the CYP-19 gene expression in response to EPA, and possibly modulates the subsequent steroidogenesis of these cells.