title: In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Suter
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical School at Houston, Houston, Texas.
authors.forename: Adi R
authors.initials: AR
authors.lastname: Abramovici
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Emily
authors.initials: E
authors.lastname: Griffin
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Molecular Medicine Program, University of Utah Health Sciences Center and Intermountain Healthcare, Salt Lake City, Utah.
authors.forename: D Ware
authors.initials: DW
authors.lastname: Branch
authors.affiliation: Department of Pediatrics, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lane
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Joan
authors.initials: J
authors.lastname: Mastrobattista
authors.affiliation: Division of Neonatology, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Aagaard
mesh_terms: D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000737:chemistry*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure; D008745:Methylation; D023421:Models, Animal; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D012326:RNA Splicing; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D002843:Chromatin; D011965:Receptors, Glucocorticoid; D009538:Nicotine
keywords: developmental origins of adult disease; epigenetics; nicotine