title: Prenatal restraint stress is associated with demethylation of corticotrophin releasing hormone (CRH) promoter and enhances CRH transcriptional responses to stress in adolescent rats.
abstract: Maternal stress can disturb normal fetal neurodevelopmental progress, and lead to negative behavioral and neuroendocrine consequences for the offspring. These effects may be related to alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Early life events disrupting the function of the HPA axis may be associated with epigenetic modification. This study investigated the effect of maternal stress on the methylation rate of the corticotrophin-releasing hormone (CRH) promoter and HPA axis response to acute stress in the adolescent offspring of Sprague-Dawley rats. Pregnant dams were randomly assigned to two groups: restraint stress group and normal control group. Adolescent male and female offspring were used from each group. The results showed that prenatal stress is associated with the demethylation of the CRH promoter, and leads to anxiety-like behaviors in adolescent life stages, as well as hyper-responsiveness of the HPA axis. Together, these results imply that prenatal stress alters the normal HPA function, which may be via the epigenetic mechanism.
authors.affiliation: Psychiatry Department, Huanshan Hospital of Fudan University, No. 12 Middle Wu Lu Mu Qi Road, Shanghai, 200040, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.forename: Yi-Yun
authors.initials: YY
authors.lastname: Cai
authors.forename: Shen-Xun
authors.initials: SX
authors.lastname: Shi
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D005260:Female; D008297:Male; D008745:Methylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000523:psychology; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone