Deciphering mRNA Translation During Sperm Capacitation: A New Frontier in Fertility Research

Male infertility accounts for approximately 50% of infertility cases, with nearly 30% remaining unexplained after standard evaluations. This highlights the need for a better understanding of sperm function to advance diagnostic and therapeutic strategies. Sperm were long considered translationally quiescent; however, emerging evidence suggests that sperm translate messenger RNAs (mRNAs) to synthesize proteins crucial for sperm functions. However, mRNA translation during capacitation remains poorly understood, despite its potential importance for fertility diagnostics. RNA-binding proteins (RBPs), small noncoding RNAs (sncRNAs), and epitranscriptomic marks regulate mRNA stability, localization, and translation initiation, modulating gene expression across reproductive tissues. Ejaculated sperm harbor initiation and elongation factors, ribosomal proteins, and other translation components, such as RBPs. Several cytoskeletal proteins and metabolic enzymes exhibit mRNA-binding activity, with the interaction of some RBPs modulated by phosphorylation during capacitation. Sperm RNA is abundant in sncRNAs, whose altered profile has been implicated in various forms of male infertility. Understanding the interplay among RBPs, the epitranscriptome, and sncRNAs could reveal mechanisms underlying sperm function and identify molecular biomarkers for infertility diagnosis. Disruptions in RNA-protein interactions may underlie idiopathic infertility, presenting opportunities for therapeutic intervention. This review highlights emerging research on sperm mRNA translation as a promising avenue for improving fertility diagnosis and treatment.