Elsevier

Biological Psychiatry

Volume 70, Issue 5, 1 September 2011, Pages 408-414
Biological Psychiatry

Priority Communication
Paternal Transmission of Stress-Induced Pathologies

https://doi.org/10.1016/j.biopsych.2011.05.005Get rights and content

Background

There has been recent interest in the possibility that epigenetic mechanisms might contribute to the transgenerational transmission of stress-induced vulnerability. Here, we focused on possible paternal transmission with the social defeat stress paradigm.

Methods

Adult male mice exposed to chronic social defeat stress or control nondefeated mice were bred with normal female mice, and their offspring were assessed behaviorally for depressive- and anxiety-like measures. Plasma levels of corticosterone and vascular endothelial growth factor were also assayed. To directly assess the role of epigenetic mechanisms, we used in vitro fertilization (IVF); behavioral assessments were conducted on offspring of mice from IVF-control and IVF-defeated fathers.

Results

We show that both male and female offspring from defeated fathers exhibit increased measures of several depression- and anxiety-like behaviors. The male offspring of defeated fathers also display increased baseline plasma levels of corticosterone and decreased levels of vascular endothelial growth factor. However, most of these behavioral changes were not observed when offspring were generated through IVF.

Conclusions

These results suggest that, although behavioral adaptations that occur after chronic social defeat stress can be transmitted from the father to his male and female F1 progeny, only very subtle changes might be transmitted epigenetically under the conditions tested.

Section snippets

Animals

All experimental C57Bl/6J male and female mice (7 weeks) were obtained from the Jackson Laboratory (Bar Harbor, Maine). Retired CD1 breeders used as the aggressors for the social defeat paradigm were obtained from Charles River (Wilmington, Massachusetts). All mice were maintained in a temperature- and humidity-controlled facility on a 12-hour light–dark cycle with food and water ad libitum. All procedures were carried out in accordance with the Institutional Animal Care and Use Committee

Results

We first tested whether depressive-like behaviors induced in normal male C57 mice could be transmitted to their offspring. We used social avoidance as our primary measure, because this has proven to be a highly reliable and long-lived consequence of chronic social defeat stress, which is reversed by chronic (not acute) antidepressant treatment (11, 12, 13, 21). As expected, 10 days of chronic social defeat stress induced robust social avoidance when compared with nondefeated control mice (n =

Discussion

Our data demonstrate that key aspects of both depressive- and anxiety-like behaviors can be transmitted to the offspring of socially defeated fathers. Although abnormalities were observed in both male and female offspring of stressed fathers, in general, a more robust phenotype was seen in the male offspring. That such behavioral abnormalities were seen only in offspring bred after the fathers experienced defeat and not before indicates that the vulnerability being transmitted is a direct

References (27)

  • A. Caspi et al.

    Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene

    Science

    (2003)
  • E.R. de Kloet et al.

    Stress and the brain: From adaptation to disease

    Nat Rev Neurosci

    (2005)
  • M.J. Meaney

    Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations

    Annu Rev Neurosci

    (2001)

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    Authors DMD, QL, and VV contributed equally to this work.

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    Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.