Role of peroxisome proliferator-activated receptor gamma (PPARγ) in the regulation of fatty acid metabolism related gene expressions in testis of men with impaired spermatogenesis

Abstract

Although male infertility is a multifactorial syndrome in which genetic factors are responsible for up to 15 % of cases, there are few studies of genes involved in lipid metabolism and male infertility. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor in testis tissue. PPARγ binds to DNA and regulates the genes for fatty acid (FA) metabolism. Thus, it has a key role in male reproduction. The current study assessed the expressions of fatty acid desaturase 2 (FADS2), elongation of very‐long‐chain fatty acids‐like 2 (ELOVL2), stearoyl-CoA desaturase-1 (SCD), and lipoprotein lipase (LPL) and incorporation of PPARγ in the promoter regions of these genes in testicular tissue biopsies from 30 infertile males who underwent testicular sperm extraction. The samples were classified into three groups: obstructive azoospermia (OA), which was the positive control (n = 10); round spermatid maturation arrest (SMA, n = 10); and Sertoli cell-only syndrome (SCOS, n = 10). There were significantly lower relative mRNA expression levels of the FADS2, ELOVL2, SCD, and LPL genes in the SCOS (P < 0.01) and SMA (P < 0.01) groups compared to the OA control group. We observed a significant decrease in chromatin incorporation of PPARγ on the promoter regions of the candidate FA metabolism genes (P < 0.05). For the first time, the present study results show that PPARγ is a strong mediator for regulation of FA metabolism in human testis tissue and we confirmed its critical role in normal spermatogenesis.