Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Department of Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran.
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Reprod Biol. 2021 Dec;21(4):100543. doi: 10.1016/j.repbio.2021.100543. Epub 2021 Sep 4.
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.
虽然男性不育是一种多因素综合征，其中遗传因素占病例的 15%，但很少有研究涉及参与脂质代谢和男性不育的基因。过氧化物酶体增殖物激活受体γ（PPARγ）是睾丸组织中的一种配体激活转录因子。PPARγ与 DNA 结合并调节脂肪酸（FA）代谢基因。因此，它在男性生殖中起着关键作用。本研究评估了脂肪酸去饱和酶 2（FADS2）、长链脂肪酸延长酶 2（ELOVL2）、硬脂酰辅酶 A 去饱和酶-1（SCD）和脂蛋白脂肪酶（LPL）的表达以及这些基因启动子区域中 PPARγ的掺入情况在 30 名接受睾丸精子提取术的不育男性的睾丸组织活检中。这些样本分为三组：梗阻性无精子症（OA），为阳性对照组（n = 10）；圆形精子细胞成熟阻滞（SMA，n = 10）；和唯支持细胞综合征（SCOS，n = 10）。与 OA 对照组相比，SCOS（P < 0.01）和 SMA（P < 0.01）组的 FADS2、ELOVL2、SCD 和 LPL 基因的相对 mRNA 表达水平显着降低。我们观察到候选 FA 代谢基因启动子区域上 PPARγ 的染色质掺入显着减少（P < 0.05）。本研究结果首次表明，PPARγ是人类睾丸组织中 FA 代谢的强有力调节因子，我们证实了其在正常精子发生中的关键作用。
