Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures

ABSTRACT: Early human pregnancy is a critical period characterized by rapid growth and extensive maternal-fetal communication that influence both maternal and fetal outcomes. Circulating extracellular vesicles (EVs) have the capacity to capture cargo that reflect these processes in real-time; however, signatures of EV subtypes during early pregnancy are poorly defined. Here we performed a comprehensive multi-omic profiling of small (~100 nm) and large (~200 nm) plasma EVs from n=10 control pregnancies (11-15 weeks) to define subtype-specific molecular signatures. Mitochondrial DNA (mtDNA) and mitochondrial protein content were higher in large EVs (lEVs). lEVs also contained a more complex set of long RNAs enriched for placental, immune, and mitochondrial-related transcripts compared with small EVs (sEVs). Proteomic profiling showed the enrichment of canonical EV markers and extracellular matrix proteins in sEVs, whereas lEVs were preferentially associated with pregnancy-specific proteins and placental hormones. MicroRNAs (miRNAs) were consistently abundant in both EV subtypes suggesting stable transcriptional regulation. These data together, support a model where small and large plasma EVs have distinct, yet complementary molecular signatures during early pregnancy, establishing a foundational framework for future studies linking EV signatures to placental dysfunction and adverse outcomes.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Hossein Fazelinia  

LAB HEAD: Rebecca A. Simmons, MD

PROVIDER: PXD074792 | Pride | 2026-10-05

REPOSITORIES: Pride