Extracellular vesicles in spontaneous preterm birth

Abstract

Feto‐maternal communication helps to maintain pregnancy and contributes to parturition at term and preterm. Endocrine and immune factor are well‐reported communication mediators. Recent advances in extracellular vesicle (EV) biology have introduced them as major communication channels between the mother and fetus. EVs are round structures with a lipid bilayer membrane. EVs are generally categorized based on their size and mode of biogenesis. The most commonly reported EVs are exosomes with a size range of 30‐160 nm that are formed inside the intraluminal vesicles of multivesicular body. Microvesicles (MVs) are larger than > 200 nm and formed by outward budding of plasma membrane. Vesicles are released from all cells and carry various factors that reflect the physiologic state of cell at the time of their release. Analysis of vesicle provides a snapshot of origin cell. Recent studies in perinatal medicine have shown that exosomes are key communicators between feto‐maternal units, and they can cross placenta. Fetal‐derived exosomes released under term labor‐associated conditions can cause parturition‐associated changes in maternal uterine tissues. Exosomes carrying inflammatory cargo can cause preterm birth in animal models suggesting their functional role in parturition. A few reports have profiled differences between exosome cargos from term and preterm pregnancies and indicated their biomarker potential to predict high‐risk pregnancy status. There are hardly any reports on MVs and their functional roles in reproduction. Herein, we review of EVs and MVs, their characteristics, function, and usefulness predicting adverse pregnancy complications such as preterm birth.

Extracellular Vesicles from Maternal Uterine Cells Exposed to Risk Factors cause Fetal Inflammatory Response

“…Exosomes are bene cial in perinatal medicine in multiple ways: 1) exosome tra cking, and changes induced at speci c sites, help to understand their functional role under certain conditions 22 ; 2) as exosomes are inert, non-immunogenic and can cross feto-maternal barriers, they can be engineered to contain speci c cargo molecules, such as drugs to address various pregnancy pathologies 53 ; and 3) exosomes are potential biomarkers as they carry snapshots of the physiological state of the cell they originated from 8,54,55 . As reported here, the functional contribution of exosomes derived from maternal uterine cells exposed to speci c conditions has now been established.…”

“…The use of exosomes as biomarkers is bene cial for indicating pregnancies that have a high risk status 8,54,55 . In pregnancy, the rst report on exosomes as biomarkers was reported by McElrath's group, where rsttrimester maternal plasma microparticle proteomic cargo with an in ammatory signature was found to carry a high risk for preterm delivery < 34 weeks 58 .…”

“…Exosomes are particles with a size range of approximately 40-160 nm and are of endosomal origin 22 . The functions of exosomes are well reported in reproductive and perinatal biology, and include acting as communication signals, biomarkers of various pregnancy pathologies and as drug delivery vehicles during pregnancy 8,18 . Using both in vitro and in vivo models, we have reported the following regarding exosome function: 1) fetal exosomes can traverse through uterine tissue barriers in animal models of pregnancy 23 ; 2) senescent fetal membrane cell-derived exosomes cause maternal uterine cell in ammation 11 ; 3) injection of in ammatory cargo-enriched exosomes cause preterm birth in animal models 24 ; and 4) fetal (placental) exosomes are predictive markers of high risk pregnancies 17,25 .…”

Placenta-Derived Exosomes as a Modulator in Maternal Immune Tolerance During Pregnancy

“…Studies on pEXO of preterm birth are rare. Unlike preeclampsia and GDM, the level of pEXO in preterm birth is significantly decreased compared to full-term pregnancy ( 218 ). Placenta senescence and fetal membrane inflammation are generally believed to be the causes of preterm birth.…”

Role of Maternal Infections and Inflammatory Responses on Craniofacial Development

“…Figure created [102], placentation [103], and maintenance of pregnancy [104]. ECVs have also been implicated in the pathogenesis of preecclampsia [105] and preterm births [106], and are touted as prognostic biomarkers [107]. While important, the role of ECVs in pregnancy is yet not fully understood [103,108,109].…”