Zaidan Hiba, Gaisler-Salomon Inna
Department of Psychology, University of Haifa, Haifa 3498838, Israel.
Department of Psychology, University of Haifa, Haifa 3498838, Israel; Department of Psychiatry, Columbia University, New York, NY 10032, USA.
Psychoneuroendocrinology. 2015 Aug;58:120-9. doi: 10.1016/j.psyneuen.2015.04.013. Epub 2015 Apr 24.
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.
人类和动物研究表明，应激易感性可能具有遗传性。我们之前已经表明，青春期雌性大鼠的慢性轻度生殖前应激（PRS）会影响第一代（F1）后代大脑中的行为和促肾上腺皮质激素释放因子1（CRF1）表达。在此，我们研究了PRS对第二代（F2）雄性和雌性后代焦虑行为和CRF1表达的影响。此外，我们评估了PRS雌性及其F1和F2后代中应激激素皮质酮（CORT）的水平，CORT是下丘脑-垂体-肾上腺（HPA）轴功能的直接标志物。F2后代在出生时CRF1 mRNA表达降低，成年后焦虑行为发生改变。PRS雌性及其F1雌性后代（而非雄性后代）的CORT水平升高。在F2代中，PRS后代的CORT水平也呈现出性别依赖性差异。这些发现表明，青春期雌性大鼠的PRS会导致行为改变，并延续至第二代后代，且对内分泌功能具有跨代效应。结合我们之前的研究结果，这些数据表明，青春期雌性大鼠的PRS会影响三代后代的行为和HPA轴功能，并凸显了研究应激对雄性和雌性后代跨代效应的重要性。
