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A novel mode of communication between blood and the germline for the inheritance of paternal experiences


van Steenwyk, Gretchen; Gapp, Katharina; Jawaid, Ali; Germain, Pierre-Luc; Manuella, Francesca; Tanwar, Deepak K; Zamboni, Nicola; Gaur, Niharika; Efimova, Anastasiia; Thumfart, Kristina; Miska, Eric A; Mansuy, Isabelle M (2019). A novel mode of communication between blood and the germline for the inheritance of paternal experiences. bioRxiv 653865, Cold Spring Harbor Laboratory.

Abstract

In many species, environmental stimuli can affect the germline and contribute to phenotypic changes in the offspring, without altering the genetic code<jats:sup>1–5</jats:sup>. 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 <jats:italic>in vivo</jats:italic> 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.

Abstract

In many species, environmental stimuli can affect the germline and contribute to phenotypic changes in the offspring, without altering the genetic code<jats:sup>1–5</jats:sup>. 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 <jats:italic>in vivo</jats:italic> 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.

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Additional indexing

Item Type:Working Paper
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:6 June 2019
Deposited On:15 Nov 2019 16:45
Last Modified:22 Sep 2023 13:13
Series Name:bioRxiv
OA Status:Green
Publisher DOI:https://doi.org/10.1101/653865
  • Content: Published Version
  • Language: English