PT  - JOURNAL ARTICLE
AU  - Katharina Gapp
AU  - Guillermo Parada
AU  - Fridolin Gross
AU  - Alberto Corcoba
AU  - Evelyn Grau
AU  - Martin Hemberg
AU  - Johannes Bohacek
AU  - Eric A. Miska
TI  - Single paternal Dexamethasone challenge programs offspring metabolism and reveals circRNAs as novel candidates in RNA-mediated inheritance
AID  - 10.1101/2021.02.10.429888
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.10.429888
4099  - http://biorxiv.org/content/early/2021/03/10/2021.02.10.429888.short
4100  - http://biorxiv.org/content/early/2021/03/10/2021.02.10.429888.full
AB  - Single traumatic events that elicit an exaggerated stress response can lead to the development of neuropsychiatric conditions. Studies in mice suggests germline RNA as a mediator of effects of chronic environmental exposures to the progeny. The effects of an acute paternal stress exposure on the germline and their potential consequences on offspring remain unknown. We find that acute administration of an agonist for the stress- sensitive Glucocorticoid receptor, using the common corticosteroid Dexamethasone, affects the RNA payload of post-meiotic transcriptionally silent, mature sperm as soon as 3 hours post exposure. It further impacts early embryonic transcriptional trajectories, as determined by single embryo sequencing, and metabolism in the offspring. Importantly, we show persistent regulation of tRNA fragments in sperm and the descendant 2-cell- embryos, suggesting actual transmission from sperm to embryo. Lastly, we unravel environmentally induced alterations in the previously underconsidered class of sperm circRNAs, and their targets in the early embryo, highlighting this class as a novel candidate in RNA-mediated inheritance.Competing Interest StatementThe authors have declared no competing interest.