Sperm RNA code in spermatogenesis and male infertility

Spermatozoa are traditionally thought to be transcriptionally inert, but recent studies have revealed the presence of sperm RNA, some of which is derived from the residues of spermatocyte transcription and some from epididymosomes. Paternal sperm RNA can be affected by external factors and further modified at the post-transcriptional level, for example N⁶-methyladenosine (m⁶A), thus shaping spermatogenesis and reproductive outcome. This review briefly introduces the origin of sperm RNA and, on this basis, summarizes the current knowledge on RNA modifications and their functional role in spermatogenesis and male infertility. The bottlenecks and knowledge gaps in the current research on RNA modification in male reproduction have also been indicated. Further investigations are needed to elucidate the functional consequences of these modifications, providing new therapeutic and preventive strategies for reproductive health and genetic inheritance.