Extracellular Vesicles, Nutrient Balance, and Redox Metabolism During Epididymal Sperm Maturation: A Perspective on the Complexity of Intercellular Interplay.

Life relies on redox reactions to sustain; however, imbalanced redox exerts stress on living beings. This is particularly pivotal as mammalian gamete sperm cells undergo functional maturation in the epididymis, preparing themselves for the long and challenging journey to begin a new life by successfully fertilizing an oocyte. Defects in epididymal sperm maturation are closely related to male infertility and reproductive health. In the epididymis, the halted translational machinery in spermatozoa while maturing in a quiescent state prompts them to immensely depend on epithelial cells for nutritional supports and information exchange. Extensive intercellular communication is therefore required between sperm and epithelial cells, and extracellular vesicles (EVs) play a crucial role as intercellular carriers. Epididymal luminal microenvironment is spatially specialized to be an acidic, decalcitonic, and pro-reductive protective milieu to prevent premature sperm dysfunction. The uniqueness of epididymal microenvironment also requires the EVs to have adaptive characteristics. Although the biogenesis and compositions of EVs in the epididymis have been reviewed elsewhere, this chapter discusses the potential role of EVs from the perspective of cellular nutrient balance of vitamins and minerals, redox metabolism, and intercellular interplay during sperm maturation to better understand the biology of epididymis in male reproduction.