Jazireian Parham, Favaedi Raha, Sadighi Gilani Mohammad Ali, Shahhoseini Maryam
Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Cell J. 2021 Dec;23(7):736-741. doi: 10.22074/cellj.2021.7634. Epub 2021 Dec 29.
Activator of CREM in the testis (ACT) is a tissue specific transcription factor which activates cAMP responsive element modulator (CREM), a key transcription factor in differentiation of round spermatids into mature spermatozoa. They bind to CRE region in the promoters of transition protein genes () and protamine genes ( and ), which are essential for sperm chromatin compaction, and regulates their transcription. This study was conducted to consider the expression of ACT and CREM and their regulatory roles on the expression of and genes in testis tissues of infertile men.
In this case-control study, testicular biopsies were collected from 40 infertile men and classified into three groups: obstructive azoospermia (OA, n=10, positive control), round spermatid maturation arrest (SMA, n=20), Sertoli cell-only syndrome (SCOS, n=10, negative control group). Using quantitative real-time polymerase chain reaction (PCR), the expression profile of and genes were assessed in testicular samples and incorporation of ACT and CREM proteins on the promoters of and genes were also evaluated by ChIP-real time PCR.
Our results demonstrated significant decrease in the expression levels of ACT, CREM and in their incorporations on their target genes in SMA group in comparison to control groups (P≤0.05).
These data confirm that there is low expression and incorporation of ACT and CREM and of their target genes in infertilities which are associated with post-meiotic arrest.
睾丸中CREM激活因子(ACT)是一种组织特异性转录因子,可激活环磷酸腺苷反应元件调节因子(CREM),后者是圆形精子细胞分化为成熟精子过程中的关键转录因子。它们与过渡蛋白基因()和鱼精蛋白基因(和)启动子中的CRE区域结合,这对精子染色质浓缩至关重要,并调节其转录。本研究旨在探讨不育男性睾丸组织中ACT和CREM的表达及其对和基因表达的调控作用。
在这项病例对照研究中,收集了40例不育男性的睾丸活检组织,并分为三组:梗阻性无精子症(OA,n = 10,阳性对照)、圆形精子细胞成熟停滞(SMA,n = 20)、唯支持细胞综合征(SCOS,n = 10,阴性对照组)。使用定量实时聚合酶链反应(PCR)评估睾丸样本中基因的表达谱,并通过染色质免疫沉淀-实时PCR评估ACT和CREM蛋白在和基因启动子上的结合情况。
我们的结果表明,与对照组相比,SMA组中ACT、CREM及其在靶基因上的结合水平显著降低(P≤0.05)。
这些数据证实,在与减数分裂后停滞相关的不育症中,ACT、CREM及其靶基因的表达和结合水平较低。