Guo Huanping, Shen Xipeng, Hu Hua, Zhou Peng, He Tong, Xia Lin, Tan Dongmei, Zhang Xi, Zhang Yunfang
Medical Center of Hematology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China.
Center for Reproductive & Genetic Medical, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China.
Mol Hum Reprod. 2022 Aug 12;28(9). doi: 10.1093/molehr/gaac031.
RNA modifications, which are introduced post-transcriptionally, have recently been assigned pivotal roles in the regulation of spermatogenesis and embryonic development. However, the RNA modification landscape in human sperm is poorly characterized, hampering our understanding about the potential role played by RNA modification in sperm. Through our recently developed high-throughput RNA modification detection platform based on liquid chromatography with tandem mass spectroscopy, we are the first to have characterized the RNA modification signature in human sperm. The RNA modification signature was generated on the basis of 49 samples from participants, including 13 healthy controls, 21 patients with asthenozoospermia (AZS) and 15 patients with teratozoospermia (TZS). In total, we identified 13 types of RNA modification marks on the total RNA in sperm, and 16 types of RNA modification marks on sperm RNA fragments of different sizes. The levels of these RNA modifications on the RNA of patients with AZS or TZS were altered, compared to controls, especially on sperm RNA fragments > 80 nt. A few types of RNA modifications, such as m1G, m5C, m2G and m1A, showed clear co-expression patterns as well as high linear correlations with clinical sperm motility. In conclusion, we characterized the RNA modification signature of human sperm and identified its correlation with sperm motility, providing promising candidates for use in clinical sperm quality assessment and new research insights for exploring the underlying pathological mechanisms in human male infertility syndromes.
RNA修饰是在转录后引入的，最近被认为在精子发生和胚胎发育的调控中起关键作用。然而，人类精子中的RNA修饰图谱特征尚不明确，这妨碍了我们对RNA修饰在精子中潜在作用的理解。通过我们最近开发的基于液相色谱-串联质谱的高通量RNA修饰检测平台，我们首次对人类精子中的RNA修饰特征进行了表征。该RNA修饰特征是基于49名参与者的样本生成的，其中包括13名健康对照、21名弱精子症（AZS）患者和1名畸形精子症（TZS）患者。我们总共在精子的总RNA上鉴定出13种RNA修饰标记，在不同大小的精子RNA片段上鉴定出16种RNA修饰标记。与对照组相比，AZS或TZS患者RNA上这些RNA修饰的水平发生了改变，尤其是在大于80 nt的精子RNA片段上。几种RNA修饰，如m1G、m5C、m2G和m1A，表现出明显的共表达模式，并且与临床精子活力具有高度线性相关性。总之，我们表征了人类精子的RNA修饰特征，并确定了其与精子活力的相关性，为临床精子质量评估提供了有前景的候选指标，并为探索人类男性不育综合征的潜在病理机制提供了新的研究见解。
