Single paternal dexamethasone challenge programs offspring metabolism and reveals multiple candidates in RNA-mediated inheritance

•Single dexamethasone injection has consequences on offspring phenotype•Dexamethasone induces dynamic changes in caput and cauda sperm serum•Dexamethasone circRNAs mature Single traumatic events that elicit an exaggerated stress response can lead to the development of neuropsychiatric conditions. Rodent studies suggested germline RNA as a mediator effects chronic environmental exposures progeny. The acute paternal exposure their potential remain be seen. We find administration agonist for stress-sensitive Glucocorticoid receptor, using common corticosteroid dexamethasone, affects payload soon 3 hr after exposure. It further impacts early embryonic transcriptional trajectories, determined by single-embryo sequencing, metabolism offspring.We show persistent regulation tRNA fragments descendant 2-cell embryos, suggesting transmission from embryo. 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