Soma-sperm communication during the journey to fertilization: addressing challenges and opportunities†

Male infertility is a significant concern in both human medicine and livestock. As it is mainly impacted by sperm quality, understanding the intrinsic characteristics of sperm that contribute to infertility is crucial. Male fertility relies on the sperm's ability to reach the site of fertilization, fertilize the oocyte, and support early embryonic development. Thus, classical sperm parameters such as motility, morphology, and the integrity of the plasma membrane, acrosome, and DNA are critical indicators of sperm quality. Recently, molecular sperm features have also been recognized as key components of sperm quality. Although sperm are transcriptionally inert and rely on external factors to shape their molecular cargo, "sperm-borne" RNAs and proteins impact embryo development. Sperm-borne molecules are acquired as sperm transit through the male and, potentially, female reproductive tracts, where they interact with components, including extracellular vesicles (EVs) from fluids within both systems. EVs play a key role in intercellular communication and carry regulatory molecules, such as proteins and miRNAs, that modulate sperm function. These interactions are vital for spermatogenesis, maturation, capacitation, and influence the sperm-borne molecular cargo. Since sperm remain interacting with the female tract, it is evident that sperm's fertility potential is also outlined in the post-ejaculatory environment. This review provides an overview of these interactions, particularly within the female reproductive system where EVs participate in sperm-borne modulation, sperm capacitation and might also be involved in sperm selection. Herein, we provide insights for further research into the mechanisms involved and their effects on sperm fertilizing potential across mammalian species.