Extracellular Vesicles in Reproductive Physiology and Pathology.

Extracellular vesicles (EVs) are lipid-bound nanostructures that play important roles in reproduction as universal mediators of bidirectional cell-to-cell communication. EVs transfer diverse cargoes between reproductive cells, influencing fundamental reproductive processes such as gametogenesis and pregnancy. In the male reproductive tract, specialized EVs such as epididymosomes and prostasomes regulate sperm activation, motility, and capacitation, exerting some of these effects within the female reproductive tract as well. In the female reproductive tract, EVs found in follicular fluid, oviduct, and uterus aid in oocyte maturation, fertilization, and the vital embryo development and embryo-maternal crosstalk necessary for successful implantation, including after in vitro fertilization. With advancing gestation, EVs continue to play crucial roles in mediating communication between maternal, placental and fetal compartments with the ultimate aim of promoting immunotolerance and development of the allogeneic fetus. Focusing on the human reproductive system, development of obstetric conditions such as preeclampsia and gestational diabetes is marked by a significant increase in EV release and systemic impacts, including endothelial dysregulation, perturbation of metabolic homeostasis and disruption to the blood-brain barrier. Disruption of EV-mediated signaling is linked to reproductive pathologies, but detailed etiologies are not yet defined. Importantly, EVs offer an exciting avenue for both biomarker discovery and therapeutic applications. Our advancing understanding of how EVs deliver their molecular cargo and influence gene expression in recipient cells holds promise for manipulating these processes and improving the diagnosis and treatment of infertility and pregnancy complications.