The developmental significance of sperm-borne ribonucleic acids and their potential for use as diagnostic markers for male factor infertility

The clinical challenge of diagnosing male factor infertility leaves several male patients with an unidentified cause of subfertility and increases time to pregnancy among couples undergoing fertility treatment. Traditionally assessed sperm characteristics inadequately predict male fertility status, reinforcing the concept that the male gamete harbors intrinsic factors that may determine its competency in fertilization and development. In addition to an intricate, epigenetically marked genome, spermatozoa carry a diverse collection of both small and large ribonucleic acids (RNAs). A growing body of literature suggests these coding and noncoding spermatozoal RNAs are functional in the early embryo, contributing to normal preimplantation development and progression. Furthermore, this dynamic population of sperm-borne RNAs is altered as maturing sperm traverse the male reproductive tract and is susceptible to various environmental influences, directing the paternal RNAs that are delivered to the oocyte. Research into such modifications has demonstrated that sperm-borne RNAs may act as mediators of epigenetic inheritance, with significant influences on offspring development and phenotype. Preliminary findings suggest that a variety of small and large RNAs are differentially expressed among the fertile and infertile groups of animals and humans and have value as diagnostic markers of male fertility status. Further investigation is necessary to better characterize the role of sperm-borne RNA elements in fertilization and development and evaluate their potential use as clinical markers for male factor infertility. (Fertil Steril Rev (R) 2021;3:11-23. (c) 2021 by American Society for Reproductive Medicine.)