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

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 (PPAR-y) is a ligand-activated transcription factor in testis tissue. PPAR-y 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 PPAR-y 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 PPAR-y on the promoter regions of the candidate FA metabolism genes (P < 0.05). For the first time, the present study results show that PPAR-y is a strong mediator for regulation of FA metabolism in human testis tissue and we confirmed its critical role in normal spermatogenesis. (c) 2021 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.