Crosstalk of extracellular vesicles in maternal-fetal interaction

Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication at the maternal-fetal interface and play indispensable roles in the establishment and maintenance of pregnancy. This review provides a mechanistic perspective on how EV-mediated signaling coordinates physiological maternal-fetal communication and how disruption of these signaling networks contributes to pregnancy-related disorders. We summarize current evidence demonstrating that EVs regulate multiple complementary biological processes, including maternal immune tolerance, trophoblast adhesion and invasion, placental angiogenesis and vascular remodeling, epithelial-stromal crosstalk, and metabolic and inflammatory adaptation, thereby maintaining maternal-fetal homeostasis. We further discuss how dysregulated EV biogenesis, cargo composition, and intercellular communication contribute to the pathogenesis of preeclampsia, gestational diabetes mellitus, preterm birth, recurrent implantation failure, and fetal growth restriction. In addition, the potential applications of EV-associated molecules as non-invasive biomarkers and the emerging use of engineered EVs for targeted therapeutic delivery are critically evaluated. Particular emphasis is placed on current challenges that limit clinical translation, including methodological heterogeneity, lack of standardized isolation and characterization protocols, insufficient biomarker validation, and pregnancy-specific safety considerations. Overall, a deeper understanding of EV-mediated maternal-fetal communication, together with methodological standardization and rigorous clinical validation, will facilitate the development of reliable EV-based diagnostic and therapeutic strategies for pregnancy-related disorders.