Embryo implantation and early pregnancy establishment lie at the intersection of metabolism, cell signaling, and immune adaptation. Recent evidence identifies extracellular vesicles (EVs),including exosomes and microvesicles, as vital mediators of communication between the maternal endometrium and the developing embryo. By transporting bioactive molecules such as proteins, lipids, and RNAs, EVs facilitate cross-kingdom molecular dialogue crucial for endometrial receptivity, trophoblast invasion, and immune tolerance. However, the impact of metabolic cues on EV dynamics remains incompletely characterized. Key questions persist on how nutrient availability, oxygen tension, and metabolic stress shape EV biogenesis, cargo composition, and downstream signaling pathways, especially during the brief peri-implantation window that is largely inaccessible to direct study. Recent advances in stem cell–derived trophoblast models, organoids, and microfluidic systems promise to bridge existing experimental gaps, enhancing our understanding of EV-mediated maternal–fetal communication.
This Research Topic aims to elucidate how metabolic states regulate extracellular vesicle signaling at the maternal–fetal interface during implantation and early placentation. It seeks to map the mechanistic links between metabolic pathways (such as glucose and lipid metabolism) and EV-mediated communication, addressing how these interactions influence trophoblast behavior, endometrial receptivity, and immune modulation. A better grasp of these processes may reveal novel biomarkers for implantation success and early pregnancy health, while also providing new therapeutic targets to mitigate complications including implantation failure, recurrent pregnancy loss, preeclampsia, and fetal growth restriction.
The scope of this Research Topic encompasses molecular, cellular, and systems-level investigations of metabolic and vesicular crosstalk in early pregnancy. To gather further insights into the metabolic–EV interface, we welcome articles addressing - but not limited to - the following themes:
o Mechanisms of EV biogenesis and cargo selection in trophoblast and endometrial cells under physiological and stressed metabolic states
o Regulation of EV release and uptake by glucose, lipid, and oxygen signaling pathways
o EV-mediated modulation of maternal immune cells, including NK cells, macrophages, and T lymphocytes, during implantation
o Application of advanced model systems - such as trophoblast organoids, endometrial assembloids, and microfluidic co-culture devices - to EV biology
o Diagnostic and prognostic potential of circulating or endometrial EVs as biomarkers of implantation and placental dysfunction
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