Faculty Collaboration Database

In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model. Birth Defects Res A Clin Mol Teratol 2015 Jul;103(7):583-8

Date

07/15/2015

Pubmed ID

26172404

Pubmed Central ID

PMC4821574

DOI

10.1002/bdra.23395

Scopus ID

2-s2.0-84937562451 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

BACKGROUND: Fetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure in utero is associated with increased risk of asthma and cognitive deficits, as well as increased expression of the hippocampal glucocorticoid receptor. We hypothesized that in utero nicotine exposure is associated with epigenetic changes in the offspring lung and brain which may contribute to a memory of this exposure

METHODS: Sprague-Dawley rat dams received either saline or 2 mg/kg of nicotine by intraperitoneal injection once daily from embryonic day 6 (e6) to e22. Pups were killed on day 1 of life, and brain and lung tissues were harvested (N = 3/ group).

RESULTS: We found that nicotine exposed offspring have altered histone modifications in the brain. Dimethylation of lysine 9 of histone H3 is decreased (0.43-fold; p = 0.03) while acetylation is increased (1.79-fold; p = 0.031). Histone deacetylase activity is significantly decreased with nicotine exposure in brain and lung (0.11-fold; p < 0.001; 0.12-fold; p < 0.001, respectively). Expression of splice variant 1.7 of the glucocorticoid receptor is reduced in the nicotine exposed offspring lung (0.25-fold; p = 0.038).

CONCLUSION: We conclude that nicotine exposure is associated with epigenetic alterations in the offspring and may lead to susceptibility to adult disease,. Our finding that in utero exposure to nicotine is associated with inhibition of histone deacetylase activity in the brain of offspring is of importance as a similar inhibition has been suggested as a mechanism for the potentiation of addiction.

Author List

Suter MA, Abramovici AR, Griffin E, Branch DW, Lane RH, Mastrobattista J, Rehan VK, Aagaard K

MESH terms used to index this publication - Major topics in bold

Acetylation
Animals
Chromatin
Female
Fetus
Gene Expression Regulation, Developmental
Male
Maternal Exposure
Methylation
Models, Animal
Nicotine
Pregnancy
RNA Splicing
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid
Transcription, Genetic