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Epigenetics of Transgenerational Transmission of In Utero Nicotine‐Induced Asthma
Author(s) -
Rehan Virender,
Liu Jei,
Sakurai Reiko,
Torday John S
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1062.5
Subject(s) - offspring , nicotine , epigenetics , medicine , in utero , endocrinology , asthma , gestation , dna methylation , pregnancy , fetus , biology , gene expression , biochemistry , genetics , gene
Whether the in utero nicotine‐induced asthma risk is transmitted transgenerationally, and whether PPARγ agonists have any effect on this transmission risk are not known. Time‐mated Sprague Dawley rat dams received either placebo or nicotine from day 6 of gestation to postnatal day (PND) 21. Following delivery, at PND21, pulmonary function tests, trachea tension studies, and expression levels of contractility proteins in the lungs and tracheas of generation 1 (F1), F2, and F3 rats were determined. As the putative basis for the transgenerational (TG) effect of nicotine on asthma, epigenetic changes in the lungs and gonads of the F1 offspring and the preventive effect of PPARγ agonist rosiglitazone (RGZ) on these epigenetic changes and TG asthma risk were determined. In comparison to the control group, with perinatal nicotine exposure only to F0 rats, 1) F1 through F3 pups demonstrated the asthma phenotype in a gender‐specific manner, with more pronounced effects in males, along with global DNA methylation increase in the testes, decrease in the ovaries, without any change in the lung. All of these changes were blocked by RGZ administration during the perinatal period. (Grant Support: HL75405, HD51857, HD058948, HL55268, and 17RT‐0170).