Circulating extracellular vesicles can transport stress signals to the male germline

Extracellular vesicles (EVs) play a key role in cell-cell communication by transporting bioactive molecules from donor to recipient cells across the body. While their involvement in somatic cells communication is well described, somatic-to-germ cells communication remains understudied. We show that small EVs (sEVs) can vehicle signals of early life stress (ELS) from circulation to sperm consequentially for the offspring. In mice, ELS persistently modifies RNA, lipids and metabolites in plasma sEVs. Chronic injection of plasma sEVs from ELS-exposed males alters the sperm transcriptome and is reflected in the transcriptome of embryos. This leads to metabolic dysfunctions in the adult offspring. These findings highlight a role of circulating sEVs in soma-to-germline communication relevant for the intergenerational transmission of ELS effects.