Alterations of RNA Modification in Mouse Germ Cell-2 Spermatids Under Hypoxic Stress.
Alterations of RNA Modification in Mouse Germ Cell-2 Spermatids Under Hypoxic Stress.
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DOI：
10.3389/fmolb.2022.871737
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发表时间：
2022
影响因子：
5
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缺氧是哺乳动物中已知的应激因素，并已被证明可能损害雄性生育能力，表现为生精功能障碍和精液质量下降。研究表明，RNA修饰，新的转录后调节因子，参与精子发生，和缺氧诱导的睾丸和精子细胞中的RNA修饰的改变可能与小鼠精子发生受损。然而，RNA修饰影响缺氧应激条件下精子发生的分子机制尚不清楚。本研究通过将小鼠生殖细胞2型精子细胞（GC-2spd）在1%O2培养箱中培养48 h或用CoCl 2处理24 h，建立了GC-2spd缺氧模型。低氧处理显著抑制GC-2spd细胞的增殖并诱导其凋亡。总RNA（2种）和差异大小的RNA片段（7种约80 nt大小的tRNA; 9种17-50 nt大小的sncRNA）的RNA修饰特征被改变，tRNA稳定性部分受到影响。此外，sncRNA的表达谱，如microRNA，tsRNA，rsRNA和ysRNA，显着调节，这可能与RNA修饰和随后的转录组学变化的改变。我们全面分析了总RNA、转运RNA、（约80 nt），和小RNA（17-50 nt）以及缺氧处理的GC-2spd细胞中sncRNA和转录组的表达谱;我们的数据表明，RNA修饰可能参与了缺氧应激条件下的细胞反应，并为更好地理解分子机制提供了基础潜在的男性不育症
Hypoxia is a known stress factor in mammals and has been shown to potentially impair male fertility, which manifests as spermatogenic dysfunction and decreased semen quality. Studies have shown that RNA modifications, the novel post-transcriptional regulators, are involved in spermatogenesis, and hypoxia-induced alterations in RNA modification in testes and sperm cells may be associated with impaired spermatogenesis in mice. However, the molecular mechanisms via which RNA modifications influence spermatogenesis under hypoxic stress conditions are unclear. In this study, we generated a mouse Germ Cell-2 spermatid (GC-2spd) hypoxia model by culturing cells in a 1% O2 incubator for 48 h or treating them with CoCl2 for 24 h. The hypoxia treatment significantly inhibited proliferation and induced apoptosis in GC-2spd cells. The RNA modification signatures of total RNAs (2 types) and differentially sized RNA fragments (7 types of approximately 80 nt-sized tRNAs; 9 types of 17–50 nt-sized sncRNAs) were altered, and tRNA stability was partially affected. Moreover, the expression profiles of sncRNAs, such as microRNAs, tsRNAs, rsRNAs, and ysRNAs, were significantly regulated, and this might be related to the alterations in RNA modification and subsequent transcriptomic changes. We comprehensively analyzed alterations in RNA modification signatures in total RNAs, tRNAs (approximately 80 nt), and small RNAs (17–50 nt) as well as the expression profiles of sncRNAs and transcriptomes in hypoxia-treated GC-2spd cells; our data suggested that RNA modifications may be involved in cellular responses under hypoxic stress conditions and could provide a basis for a better understanding of the molecular mechanisms underlying male infertility.