Prereproductive stress in adolescent female rats affects behavior and corticosterone levels in second-generation offspring

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Human and animal studies indicate that vulnerability to stress may be heritable. We have previously shown that chronic, mild prereproductive stress (PRS) in adolescent female rats affects behavior and corticotropin releasing factor 1 (CRF1) expression in the brain of first-generation (F1) offspring. Here, we investigated the effects of PRS on anxiogenic behavior and CRF1 expression in male and female second-generation (F2) offspring. Furthermore, we assessed levels of the stress hormone corticosterone (CORT), a direct marker of hypothalamic-pituitary-adrenal (HPA) axis function, in PRS females and their F1 and F2 progeny. F2 offspring demonstrated decreased CRF1 mRNA expression at birth, and alterations in anxiogenic behavior in adulthood. CORT levels were elevated in PRS females and in their F1 female, but not male, offspring. In F2, CORT levels in PRS offspring also varied in a sex-dependent manner. These findings indicate that PRS in adolescent females leads to behavioral alterations that extend to second-generation offspring, and has transgenerational effects on endocrine function. Together with our previous findings, these data indicate that PRS to adolescent females affects behavior and HPA axis function across three generations, and highlight the importance of examining the transgenerational effects of stress in both male and female offspring.

Original languageEnglish
Pages (from-to)120-129
Number of pages10
StatePublished - 1 Aug 2015

Bibliographical note

Funding Information:
This study was supported by Israel Science Foundation grant 484/10 to Inna Gaisler-Salomon. This funding source had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Publisher Copyright:
© 2015 Elsevier Ltd.


  • Behavior
  • Corticosterone
  • F2
  • Rat
  • Sex differences
  • Stress
  • Transgenerational

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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