Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Molecular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
PLoS One. 2020 Apr 30;15(4):e0232357. doi: 10.1371/journal.pone.0232357. eCollection 2020.
One of the main molecular causes that contributes to varicocele-related male infertility is excess production of reactive oxygen species (ROS). It is believed that hypoxia is an important stimulator of ROS in this condition. Recently, the significant roles of long non-coding RNAs (lncRNAs) in hypoxia response have emerged. Despite the investigation of hypoxia, there is scant information about the role of hypoxia-responding lncRNAs in varicocele-related male infertility. In the present study, we deduced eight hypoxia-responding lncRNAs based on high-throughput RNA sequencing data from two Gene Expression Omnibus (GEO) datasets. We used qRT-PCR to assess the expression levels of some of these lncRNAs in 42 ejaculated spermatozoa samples from 25 infertile men with varicocele and 17 fertile men as controls. We identified significant increases in expression levels of hypoxia-related lncRNAs, MIR210HG and MLLT4-AS1 in ejaculated spermatozoa of infertile men with varicocele. These lncRNAs also showed significant positive correlations with ROS levels and meaningful negative correlations with sperm parameters (count and motility). Besides, in silico studies identified several hypoxia response elements (HREs) within selected lncRNAs promoters. Delineation of hypoxia-related lncRNAs in varicocele-related infertility provides a valuable insight into male infertility.
导致精索静脉曲张相关男性不育的主要分子原因之一是活性氧（ROS）的过度产生。据信，缺氧是这种情况下 ROS 的重要刺激因素。最近，长非编码 RNA（lncRNA）在缺氧反应中的重要作用已经显现出来。尽管已经对缺氧进行了研究，但关于与精索静脉曲张相关的男性不育中缺氧反应的 lncRNA 的作用知之甚少。在本研究中，我们根据两个基因表达综合数据库（GEO）数据集的高通量 RNA 测序数据推导出了 8 个缺氧反应 lncRNA。我们使用 qRT-PCR 评估了这些 lncRNA 中的一些在 42 个来自 25 名精索静脉曲张不育男性和 17 名正常生育男性的射出精液样本中的表达水平。我们发现，精索静脉曲张不育男性射出精液中的缺氧相关 lncRNA，MIR210HG 和 MLLT4-AS1 的表达水平显著升高。这些 lncRNA 还与 ROS 水平呈显著正相关，与精子参数（计数和活力）呈显著负相关。此外，计算机研究在选定的 lncRNA 启动子内识别出了几个缺氧反应元件（HREs）。阐明精索静脉曲张相关不育症中的缺氧相关 lncRNA 为男性不育症提供了有价值的见解。
