不育男性睾丸组织BRDT基因的表观遗传失调:病例对照研究

Fereshteh Kohandani, Parham Jazireian, R. Favaedi, M. S. Sadighi Gilani, S. M. Moshtaghioun, M. Shahhoseini
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引用次数: 0

摘要

目的溴域睾丸相关蛋白(BRDT)是睾丸特异性的溴域和外端结构域(BET)蛋白家族成员,参与精子发生,更具体地说,参与染色质重塑。在减数分裂后的生精细胞中,BRDT蛋白与高乙酰化的组蛋白结合,并促进它们被过渡蛋白(TPs)取代,特别是对染色质凝聚至关重要的精蛋白。目前的研究旨在评估BRDT在不育男性睾丸组织中的表达和表观遗传谱。材料与方法本病例对照研究分为3组:阳性对照组:阻塞性无精子症(OA, n=10)、圆形精子成熟阻滞组(SMA, n=10)和阴性对照组:仅支持细胞综合征(SCOS, n=10)。采用实时定量聚合酶链反应(PCR),生成BRDT基因的表达谱。采用ChIP-real - time PCR检测BRDT启动子区域的组蛋白标记:H3K9ac、H3K9me3、H3K4me3、H3K27me3。结果我们的数据显示,与阳性对照组相比,SMA组的BRDT表达降低,这一发现与该组的ChIP结果一致。结论BRDT基因在精子发生过程中起重要作用,由于表观遗传信号异常导致BRDT基因表达减少可能与男性不育有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epigenetic Dysregulation of BRDT Gene in Testis Tissues of Infertile Men: Case-Control Study
Objective Bromodomain testis associated (BRDT), a testis-specific member of the Bromo- and Extra-Terrminal domain (BET) protein family, is involved in spermatogenesis and, more specifically, chromatin remodeling. In the post-meiotic spermatogenic cells, BRDT protein binds to the hyperacetylated histones and facilitates their replacement with transition proteins (TPs), particularly protamines, which are essential for chromatin condensation. The current research was conducted to assess the expression and epigenetic profile of BRDT in the testis tissues of infertile men. Materials and Methods In this case-control study, three groups were included: positive control group: obstructive azoospermia (OA, n=10), round spermatid maturation arrest group (SMA, n=10) and negative control group: sertoli cell- only syndrome (SCOS, n=10). Using quantitative real-time polymerase chain reaction (PCR), the expression profile of BRDT was generated. Also, ChIP-real time PCR was used to measure the following histone marks: H3K9ac, H3K9me3, H3K4me3, H3K27me3 on the promoter region of BRDT. Results Our data indicated that BRDT expression decreased in the SMA group in comparison with the positive control group and this finding is in line with the ChIP results obtained in this group. Conclusion Based on these data, we postulate that BRDT gene has a vital role in the spermatogenesis and its decreased expression due to an aberrant epigenetic signaling might be associated with male infertility.
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