Alteration of RNA modification signature in human sperm correlates with sperm motility

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 m(1)G, m(5)C, m(2)G and m(1)A, 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.