Prereproductive stress to female rats alters corticotropin releasing factor type 1 expression in ova and behavior and brain corticotropin releasing factor type 1 expression in offspring

摘要

Background Human and animal studies indicate that vulnerability to stress may be heritable and that changes in germline may mediate some transgenerational effects. Corticotropin releasing factor type 1 (CRF1) is a key component in the stress response. We investigated changes in CRF1 expression in brain and ova of stressed female rats and in the brain of their neonate and adult offspring. Behavioral changes in adulthood were also assessed. Methods Adult female rats underwent chronic unpredictable stress. We extracted mature oocytes and brain regions from a subset of rats and mated the rest 2 weeks following the stress procedure. CRF1 expression was assessed using quantitative reverse-transcription polymerase chain reaction. Tests of anxiety and aversive learning were used to examine behavior of offspring in adulthood. Results We show that chronic unpredictable stress leads to an increase in CRF1 messenger RNA expression in frontal cortex and mature oocytes. Neonatal offspring of stressed female rats show an increase in brain CRF1 expression. In adulthood, offspring of stressed female rats show sex differences in both CRF1 messenger RNA expression and behavior. Moreover, CRF1 expression patterns in frontal cortex of female offspring depend upon both maternal and individual adverse experience. Conclusions Our findings demonstrate that stress affects CRF1 expression in brain but also in ova, pointing to a possible mechanism of transgenerational transmission. In offspring, stress-induced changes are evident at birth and are thus unlikely to result from altered maternal nurturance. Finally, brain CRF1 expression in offspring depends upon gender and upon maternal and individual exposure to adverse environment.