title: Perinatal nicotine-induced transgenerational asthma.
abstract: Asthma is a major public health hazard worldwide. Its transgenerational inheritance has been inferred from epidemiological studies. More recently, using nicotine as a proxy for maternal smoking, we have demonstrated that an asthma-like phenotype can be inherited by rat offspring for up to two generations, i.e., multigenerationally, after the initial intrauterine exposure. We hypothesized that asthma transmission to offspring following perinatal nicotine exposure is not restricted up to F2 generation, but it also extends to subsequent generations. To test this hypothesis, using a well-established rat model of nicotine exposure-induced childhood asthma, we determined if perinatal nicotine exposure of F0 gestating dams would transmit asthma transgenerationally to F3 offspring. We now extend our findings to third-generation offspring, including abnormal pulmonary function, particularly as it relates to the occurrence in the upper airway exclusively in males, and to its effects on molecular functional markers (fibronectin and peroxisome proliferator-activated receptor γ), previously shown to be consistent with the asthma phenotype, herein expressed in fibroblasts isolated from the lung. These data, for the first time, demonstrate the transgenerational transmission of the asthma phenotype to F3 offspring following perinatal nicotine exposure of F0 dams.
authors.affiliation: Dept. of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 W. Carson St., Torrance, CA 90502-2006. vrehan@labiomed.org.
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Reiko
authors.initials: R
authors.lastname: Sakurai
authors.forename: John S
authors.initials: JS
authors.lastname: Torday
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000209:etiology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure; D009538:Nicotine / Q000009:adverse effects*; D047495:PPAR gamma / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012907:Smoking / Q000009:adverse effects*
chemical_list: D005353:Fibronectins; D047495:PPAR gamma; D009538:Nicotine
keywords: maternal smoking; peroxisome proliferator-activated receptor γ; pulmonary function
references.citation: Allergy. 2004 May;59(5):469-78
references.pmid: 15080825
references.citation: Chest. 2004 Oct;126(4):1071-8
references.pmid: 15486366
references.citation: Am J Respir Cell Mol Biol. 2013 Jan;48(1):53-62
references.pmid: 23002101
references.citation: Exp Lung Res. 1984;7(3-4):187-94
references.pmid: 6549292
references.citation: Chest. 2006 Jul;130(1 Suppl):4S-12S
references.pmid: 16840363
references.citation: Paediatr Perinat Epidemiol. 1992 Apr;6(2):240-53
references.pmid: 1584725
references.citation: Exp Lung Res. 2010 Sep;36(7):390-8
references.pmid: 20715982
references.citation: PLoS One. 2013;8(1):e55387
references.pmid: 23359474
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L130-5
references.pmid: 12060569
references.citation: Placenta. 2012 Nov;33 Suppl 2:e40-4
references.pmid: 22902003
references.citation: S Afr Med J. 1993 Mar;83(3):195-8
references.pmid: 8511687
references.citation: Eur J Hum Genet. 2002 Nov;10(11):682-8
references.pmid: 12404098
references.citation: Am J Respir Crit Care Med. 2008 Mar 15;177(6):567-73
references.pmid: 18187692
references.citation: Endocrinology. 2010 Jan;151(1):7-13
references.pmid: 19887563
references.citation: Lung. 2009 Sep-Oct;187(5):281-9
references.pmid: 19641967
references.citation: J Toxicol Environ Health B Crit Rev. 2008 May;11(5-6):373-517
references.pmid: 18470797
references.citation: Arch Dis Child. 2003 Dec;88(12):1086-90
references.pmid: 14670776
references.citation: Epigenetics. 2011 Jul;6(7):838-42
references.pmid: 21637037
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L611-8
references.pmid: 12754191
references.citation: Pediatr Res. 2007 Jul;62(1):2-7
references.pmid: 17515838
references.citation: Toxicol Appl Pharmacol. 1995 May;132(1):63-71
references.pmid: 7747286
references.citation: Am J Epidemiol. 2009 Dec 15;170(12):1486-93
references.pmid: 19880541
references.citation: BMC Med. 2012 Oct 30;10:129
references.pmid: 23106849
references.citation: Front Genet. 2011 Nov 22;2:84
references.pmid: 22303378
references.citation: J Allergy Clin Immunol. 2011 Jan;127(1):262-4, 264.e1
references.pmid: 21094522
references.citation: Pediatr Pulmonol. 2009 Jul;44(7):635-44
references.pmid: 19514059
references.citation: BMC Med. 2013 Feb 04;11:27
references.pmid: 23379695
references.citation: J Clin Invest. 2008 Oct;118(10):3462-9
references.pmid: 18802477
references.citation: Eur J Hum Genet. 2006 Feb;14(2):159-66
references.pmid: 16391557
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9143-8
references.pmid: 22615374
references.citation: Toxicol Appl Pharmacol. 1999 Mar 15;155(3):253-60
references.pmid: 10079211
references.citation: Am J Epidemiol. 2007 Sep 15;166(6):679-86
references.pmid: 17625224
references.citation: Pediatr Pathol Mol Med. 2003 May-Jun;22(3):189-207
references.pmid: 12746170
references.citation: Am J Physiol Lung Cell Mol Physiol. 2011 May;300(5):L710-7
references.pmid: 21355041
references.citation: Annu Rev Genomics Hum Genet. 2008;9:233-57
references.pmid: 18767965
references.citation: Am J Respir Crit Care Med. 2006 Jun 1;173(11):1255-63
references.pmid: 16484675
references.citation: Acta Biotheor. 2001 Mar;49(1):53-9
references.pmid: 11368478
references.citation: Endocrinology. 2010 Dec;151(12):5617-23
references.pmid: 20943806
references.citation: Nat Med. 2012 Sep;18(9):1369-77
references.pmid: 22941276
references.citation: Thorax. 2000 Apr;55(4):271-6
references.pmid: 10722765
references.citation: Am Rev Respir Dis. 1992 May;145(5):1129-35
references.pmid: 1586058
references.citation: Chest. 2005 Apr;127(4):1232-41
references.pmid: 15821200
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18704-9
references.pmid: 19843690
references.citation: Allergy. 2012 Jul;67(7):904-10
references.pmid: 22583153
references.citation: Am J Physiol Lung Cell Mol Physiol. 2011 Nov;301(5):L721-30
references.pmid: 21821729