Advances in sperm transcription and translation activities: From traditional views to new discoveries

Traditionally, mammalian spermatozoa have been viewed as transcriptionally and translationally inert cells that merely deliver paternal DNA to the oocyte. However, the advent of high-throughput RNA sequencing and mass-spectrometry-based proteomics has fundamentally revised this paradigm. Mature sperm are now known to harbor a diverse and dynamic repertoire of coding and non-coding RNAs-including mRNAs, lncRNAs, miRNAs, piRNAs, tsRNAs and circRNAs-as well as a rich proteome and specialized ribosomes that together support tightly regulated post-testicular functions. These RNA and protein cargos originate from spermatogenesis, epididymal extracellular vesicle-mediated transfer, and possibly limited de novo transcription, and are further shaped by environmental and lifestyle factors. Functionally, sperm RNAs and translational activities contribute to sperm maturation, motility, capacitation, fertilization, and early embryonic development, and are implicated in intergenerational epigenetic inheritance. Comparative transcriptomic and proteomic studies across humans and livestock demonstrate that specific RNA and protein signatures distinguish high-from low-fertility males, highlighting their potential as biomarkers for male fertility assessment and as companion tools for assisted reproduction. Emerging evidence that cytoplasmic and mitochondrial translation can occur during capacitation further underscores that spermatozoa are dynamic cells capable of context-dependent protein synthesis. This review synthesizes current advances in sperm transcriptional and translational biology, with a focus on the origin and regulation of sperm RNAs, the role of specialized ribosomes and translation factors, environmental modulation of these processes, and the translational potential of sperm RNA and protein profiles as diagnostic, prognostic, and therapeutic targets in male reproductive medicine.