Poster Presentation The International Congress of Neuroendocrinology 2014

Prenatal glucocorticoids exposure induces depressive behavior and upregulation of CRH and CRHR1in hippocampus of offspring.  (#188)

Xin Ni , Yongjun Xu , Hui Sheng

Prenatal glucocorticoids (GCs) exposure has been shown to be associated with high risk of depression in offspring. However, the mechanisms involved remains largely unknown. Given that overexpression of corticotropin-releasing hormone (CRH) and CRH type-1 receptor (CRHR1) in hippocampus is involved in pathophysiology of depression, the objectives of present study were to investigate whether prenatal GCs exposure alters depressive behavior and CRH and CRHR1 expression in hippocampus in adult offspring rats, and determine whether these alterations can be transmissible to a second generation. Pregnant rats received dexamethasone (DEX) (0.1 mg/kg/day) in the third week of pregnancy or vehicle. Prenatal DEX treatment elicited depressive behavior, and increased the expression of CRH and CRHR1 in hippocampus in adult offspring. The alterations in CRHR1 expression may be linked to demethylation at 2 specific sites of CpG island of CRHR1 promoter in hippocampus in DEX groups. We further investigated the effects of prenatal DEX treatment on the second-generation offspring rats which can be assigned to CON♂-CON♀, CON♂-DEX♀, DEX♂-CON♀, and DEX♂-DEX♀ groups. We found that the rats in CON♂-DEX♀ and DEX♂-DEX♀ groups also showed increased depressive behavior. Moreover, CRH expression in hippocampus increased in both male and female rats of these two groups, while CRHR1 expression only increased in male rats. Our results showed that the effects of prenatal GCs exposure on depressive behavior and CRH system expression are not limited to the exposed first generation but can be transmissible to a second generation through parental lineages, especial the maternal line, which suggests that the transgenerational transmission of depressive behavior may be associated with the long-term programming effect of prenatal GCs exposure on CRH-CRHR1 system.