Extracellular vesicles in reproduction and pregnancy

Abstract

Extracellular vesicles (EVs) are small, lipid-bound packages that are secreted by all cell types and have been implicated in many diseases, such as cancer and neurodegenerative disorders. Though limited, an exciting new area of EV research focuses on their role in the reproductive system and pregnancy. In males, EVs have been implicated in sperm production and maturation. In females, EVs play a vital role in maintaining reproductive organ homeostasis and pregnancy, including the regulation of folliculogenesis, ovulation, and embryo implantation. During the development and maintenance of a pregnancy, the placenta is the main form of communication between the mother and the developing fetus. To support the developing fetus, the placenta will act as numerous vital organs until birth, and release EVs into the maternal and fetal bloodstream. EVs play an important role in cell-to-cell communication and may mediate the pathophysiology of pregnancy-related disorders such as preeclampsia, gestational diabetes mellitus, preterm birth, and intrauterine growth restriction, and potentially serve as noninvasive biomarkers for these conditions. In addition, EVs may also mediate processes involved in both male and female infertility. Together, the EVs secreted by both the male and female reproductive tracts work to promote reproductive fertility and play vital roles in mediating maternal-fetal crosstalk and pregnancy maintenance.

Streamlined Analysis of Maternal Plasma Indicates Small Extracellular Vesicles are Significantly Elevated in Early-Onset Preeclampsia

“…Upon their release into circulation, EVs are capable of carrying a wide variety of cargo capable of participating in cellular signaling [37, 42-47, 58, 77, 78]. There is now widespread recognition that EVs less than 200 nm in size, defined as sEVs, significantly contribute to cell-to-cell In the setting of human pregnancy, plasma EV concentrations are known to increase physiologically [48,52,[81][82][83][84]. As a healthy pregnancy progresses, the placenta releases EVs into circulation as a means of communicating with maternal organs and promoting the various physiologic adaptations necessary to support the growing fetus [48,51,52,85].…”

“…As a healthy pregnancy progresses, the placenta releases EVs into circulation as a means of communicating with maternal organs and promoting the various physiologic adaptations necessary to support the growing fetus [48,51,52,85]. In vitro studies support advantageous sEV signaling in pregnancy: placental sEVs may be beneficially immunomodulatory and may function to enhance maternal spiral artery remodeling [77,81,84]. Conversely, there is now also wide-spread evidence demonstrating the pathologic impact of sEV signaling in the pathogenesis of pregnancy-related disorders including gestational diabetes and PE [23,41,42,54,55,[78][79][80][86][87][88][89][90][91][92].…”