Melissa A Suter1, Adi R Abramovici2, Emily Griffin1, D Ware Branch3, Robert H Lane4, Joan Mastrobattista1, Virender K Rehan5, Kjersti Aagaard1. 1. Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Baylor College of Medicine, Houston, Texas. 2. Department of Obstetrics and Gynecology, University of Texas Medical School at Houston, Houston, Texas. 3. 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. 4. Department of Pediatrics, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin. 5. Division of Neonatology, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
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.
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.
Authors: Amir Levine; Yanyou Huang; Bettina Drisaldi; Edmund A Griffin; Daniela D Pollak; Shiqin Xu; Deqi Yin; Christine Schaffran; Denise B Kandel; Eric R Kandel Journal: Sci Transl Med Date: 2011-11-02 Impact factor: 17.956
Authors: Xingrao Ke; Michelle E Schober; Robert A McKnight; Shannon O'Grady; Diana Caprau; Xing Yu; Christopher W Callaway; Robert H Lane Journal: Physiol Genomics Date: 2010-04-13 Impact factor: 3.107
Authors: Yu-Jing Gao; Alison C Holloway; Li-Ying Su; Kumiko Takemori; Chao Lu; Robert M K W Lee Journal: Eur J Pharmacol Date: 2008-06-03 Impact factor: 4.432
Authors: Kakkad Regha; Mathew A Sloane; Ru Huang; Florian M Pauler; Katarzyna E Warczok; Balázs Melikant; Martin Radolf; Joost H A Martens; Gunnar Schotta; Thomas Jenuwein; Denise P Barlow Journal: Mol Cell Date: 2007-08-03 Impact factor: 17.970
Authors: Hector Mendez-Figueroa; Suneet P Chauhan; Mary C Tolcher; Alireza A Shamshirsaz; Haleh Sangi-Haghpeykar; Ryan M Pace; Derrick M Chu; Kjersti Aagaard Journal: Obstet Gynecol Date: 2019-11 Impact factor: 7.661
Authors: Ina Kreyberg; Karen E S Bains; Kai-H Carlsen; Berit Granum; Hrefna K Gudmundsdóttir; Guttorm Haugen; Gunilla Hedlin; Katarina Hilde; Christine M Jonassen; Live S Nordhagen; Björn Nordlund; Katrine D Sjøborg; Håvard O Skjerven; Anne C Staff; Cilla Söderhäll; Riyas M Vettukatil; Karin C Lødrup Carlsen Journal: ERJ Open Res Date: 2019-04-08