PT  - JOURNAL ARTICLE
AU  - Gretchen van Steenwyk
AU  - Katharina Gapp
AU  - Ali Jawaid
AU  - Pierre-Luc Germain
AU  - Francesca Manuella
AU  - Deepak K. Tanwar
AU  - Nicola Zamboni
AU  - Niharika Gaur
AU  - Anastasiia Efimova
AU  - Kristina Thumfart
AU  - Eric A. Miska
AU  - Isabelle M. Mansuy
TI  - A novel mode of communication between blood and the germline for the inheritance of paternal experiences
AID  - 10.1101/653865
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 653865
4099  - http://biorxiv.org/content/early/2019/06/06/653865.short
4100  - http://biorxiv.org/content/early/2019/06/06/653865.full
AB  - In many species, environmental stimuli can affect the germline and contribute to phenotypic changes in the offspring, without altering the genetic code1–5. So far, little is known about which biological signals can link exposure to germ cells. Using a mouse model of postnatal trauma with transgenerational effects, we show that exposure alters lipid-based metabolites in blood of males and their non-exposed offspring. Comparable alterations are validated in serum and saliva of orphan children exposed to trauma. Peroxisome proliferator-activated receptor (PPAR) is identified as mediating the effects of metabolites alterations. Mimicking PPAR activation with a dual PPARα/γ agonist in vivo induces changes in the sperm transcriptome similarly to trauma, and reproduces metabolic phenotypes in the offspring. Injecting serum collected from adult males exposed to postnatal trauma into controls recapitulates metabolic phenotypes in the offspring. These results suggest conserved effects of early life adversity on blood metabolites, and causally involve paternal blood factors and PPAR nuclear receptor in phenotype heritability.