Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses

Hamisu M. Salihu; Arnut Paothong; Rachita Das; Lindsey M. King; Anupam Pradhan; Bridget Riggs; Eknath Naik; Erin M. Siegel; Valerie E. Whiteman

doi:10.1515/jpm-2016-0279

Article

Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses

Hamisu M. Salihu , Arnut Paothong , Rachita Das , Lindsey M. King , Anupam Pradhan , Bridget Riggs , Eknath Naik , Erin M. Siegel and Valerie E. Whiteman

Published/Copyright: January 28, 2017

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From the journal Journal of Perinatal Medicine Volume 45 Issue 9

Abstract

Aim:

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.

Keywords: Fetal brain regulatory genes; intrauterine tobacco exposure; neonatal umbilical cord blood

Corresponding author: Hamisu M. Salihu, MD, PhD, Department of Family and Community Medicine, Baylor College of Medicine, 3701 Kirby Drive, Suite 600, Houston, TX, USA, Tel.: +713-798-7646, Fax: +713-798-2725

Acknowledgments

This work was supported by the James and Esther King Biomedical Research Program, Florida Department of Health (grant number 4KB03 and 1KG14-33987) and the University of South Florida Neuroscience Collaborative – Seed Grant Program and the University of South Florida College of Public Health Interdisciplinary Research Development Grant (IDRG).

Author’s statement

Conflict of interest: Authors state no conflict of interest.
Material and methods: Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.

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Received: 2016-8-18

Accepted: 2016-12-21

Published Online: 2017-1-28

Published in Print: 2017-12-20

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Articles in the same Issue

https://doi.org/10.1515/jpm-2016-0279

Keywords for this article

Fetal brain regulatory genes; intrauterine tobacco exposure; neonatal umbilical cord blood