title: Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses.
abstract: OBJECTIVE
  We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes.
  
  
  METHODS
  At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA. We then employed the quantitative polymerase chain reaction (QPCR) analyses and the comparative CT method to calculate the relative gene expression of selected fetal brain regulatory genes responsible for (1) brain growth (brain-derived neutrotrophic factor, BDNF), (2) myelination (proteolipidic protein 1, PLP1 and myelin basic protein, MBP), and (3) neuronal migration and cell-cell interactions during fetal brain development or RLN. The χ2-test, analysis of variance (ANOVA), and the Grubb test were used to evaluate the relationship between prenatal smoking status and relative gene expression levels. Further analysis using bootstrapping was performed to assess the precision of our estimates.
  
  
  RESULTS
  Of the 39 maternal-infant dyads included in this study, 25.6% were non-smokers, 43.6% were passive smokers and 30.8% were active smokers. The results showed down-regulation of the selected fetal brain regulatory genes among active smokers.
  
  
  CONCLUSIONS
  These findings represent preliminary evidence in humans that intrauterine tobacco exposure impacts fetal brain programming. Future studies are warranted to examine whether our findings represent potential mechanisms through which adverse childhood/adult-onset cognitive and behavioral outcomes that have been previously linked to intrauterine exposure occur.
authors.affiliation: .
authors.forename: Hamisu M
authors.initials: HM
authors.lastname: Salihu
authors.affiliation: .
authors.forename: Arnut
authors.initials: A
authors.lastname: Paothong
authors.affiliation: .
authors.forename: Rachita
authors.initials: R
authors.lastname: Das
authors.affiliation: .
authors.forename: Lindsey M
authors.identifier: http://orcid.org/0000-0002-5986-954X
authors.initials: LM
authors.lastname: King
authors.affiliation: .
authors.forename: Anupam
authors.initials: A
authors.lastname: Pradhan
authors.affiliation: .
authors.forename: Bridget
authors.initials: B
authors.lastname: Riggs
authors.affiliation: .
authors.forename: Eknath
authors.initials: E
authors.lastname: Naik
authors.affiliation: .
authors.forename: Erin M
authors.initials: EM
authors.lastname: Siegel
authors.affiliation: .
authors.forename: Valerie E
authors.initials: VE
authors.lastname: Whiteman
mesh_terms: D000328:Adult; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects; D009185:Myelin Proteins / Q000097:blood*; D011247:Pregnancy; D012065:Relaxin / Q000097:blood*; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009185:Myelin Proteins; C095067:RLN1 protein, human; D014028:Tobacco Smoke Pollution; C579455:BDNF protein, human; D012065:Relaxin
keywords: Fetal brain regulatory genes; intrauterine tobacco exposure; neonatal umbilical cord blood