RT Journal Article
SR Electronic
T1 A novel mode of communication between blood and the germline for the inheritance of paternal experiences
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 653865
DO 10.1101/653865
A1 Gretchen van Steenwyk
A1 Katharina Gapp
A1 Ali Jawaid
A1 Pierre-Luc Germain
A1 Francesca Manuella
A1 Deepak K. Tanwar
A1 Nicola Zamboni
A1 Niharika Gaur
A1 Anastasiia Efimova
A1 Kristina Thumfart
A1 Eric A. Miska
A1 Isabelle M. Mansuy
YR 2019
UL http://biorxiv.org/content/early/2019/06/06/653865.abstract
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.