Skip to main content

Ethanol toxicity affects olfactory receptor genes in forebrain of fetal mice

Molecular & Cellular Toxicology volume 11, pages 55–60 (2015)Cite this article

Abstract

Toxicity of ethanol can lead to behavioral and cognitive impairments of fetus. The aim of this current study was to investigate the alteration of genes at developing fetal brain by maternal binge alcohol consumption. Genome-wide transcriptional analysis revealed a set of differentially expressed genes (20 upregulated and 21 down-regulated; 1.5-fold cut-off) on embryonic day 15 (ED15) in the developing fetal brain. The gene ontology analysis revealed the associations of these genes with sensory perception, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that they were correlated with olfactory transduction. Six olfactory receptor genes (Olfr960, Olfr1342, Olfr43, Olfr836, Olfr1262 and Olfr1419) encoding proteins involved in the olfactory transduction pathway showed reduced expression levels. The downregulation of these olfactory receptor genes may cause odor identification defects as well as abnormalities in the olfactory system. Our findings aid in the elucidation of the molecular mechanism underlying the defective olfactory processing that occurs following prenatal alcohol exposure.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Joya, X., Garcia-Algar, O., Salat-Batlle, J., Pujades, C. & Vall, O. Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention. Birth Defects Research Part A: Clinical and Molecular Teratology n/a:n/a-n/a (2014).

    Google Scholar 

  2. Burd, L. et al. Congenital heart defects and fetal alcohol spectrum disorders. Congenit Heart Dis 2:250–255 (2007).

    Article  PubMed  Google Scholar 

  3. Maier, S. E., Miller, J. A. & West, J. R. Prenatal bingelike alcohol exposure in the rat results in region-specific deficits in brain growth. Neurotoxicol Teratol 21:285–291 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. Ramadoss, J. & Magness, R. R. Vascular effects of maternal alcohol consumption. Vol. 303 (2012).

  5. Riley, E. P. & McGee, C. L. Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Exp Biol Med (Maywood) 230:357–365 (2005).

    CAS  Google Scholar 

  6. Sawant, O. B. et al. Different patterns of regional Purkinje cell loss in the cerebellar vermis as a function of the timing of prenatal ethanol exposure in an ovine model. Neurotoxicol Teratol 35:7–13 (2013).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Sokol, R. J., Delaney-Black, V. & Nordstrom, B. Fetal alcohol spectrum disorder. JAMA 290:2996–2999 (2003).

    Article  CAS  PubMed  Google Scholar 

  8. Weinberg, J., Sliwowska, J. H., Lan, N. & Hellemans, K. G. Prenatal alcohol exposure: foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome. J Neuroendocrinol 20:470–488 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. Mattson, S. N., Crocker, N. & Nguyen, T. T. Fetal alcohol spectrum disorders: neuropsychological and behavioral features. Neuropsychol Rev 21:81–101 (2011).

    Article  PubMed Central  PubMed  Google Scholar 

  10. Mattson, S. N. & Riley, E. P. The quest for a neurobehavioral profile of heavy prenatal alcohol exposure. Alcohol Res Health 34:51–55 (2011).

    PubMed Central  PubMed  Google Scholar 

  11. Murthy, P., Kudlur, S., George, S. & Mathew, G. A Clinical Overview of Fetal Alcohol Syndrome. Addictive Disorders & Their Treatment 8:1–12 10.1097/ADT.1090b1013e318163b318062 (2009).

    Article  Google Scholar 

  12. Sowell, E. R. et al. Mapping white matter integrity and neurobehavioral correlates in children with fetal alcohol spectrum disorders. J Neurosci 28:1313–1319 (2008).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Guerri, C. Mechanisms involved in central nervous system dysfunctions induced by prenatal ethanol exposure. Neurotox Res 4:327–335 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Courtney, K. E. & Polich, J. Binge drinking in young adults: Data, definitions, and determinants. Psychol Bull 135:142–156 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  15. Jung, K. H. et al. Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicology in Vitro 24:1696–1704 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Young, J. M. & Trask, B. J. The sense of smell: genomics of vertebrate odorant receptors. Human Molecular Genetics 11:1153–1160 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Bower, E., Szajer, J., Mattson, S. N., Riley, E. P. & Murphy, C. Impaired odor identification in children with histories of heavy prenatal alcohol exposure. Alcohol 47:275–278 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Gaillard, I., Rouquier, S. & Giorgi, D. Olfactory receptors. Cell Mol Life Sci 61:456–469 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Hussain, A., Saraiva, L. R. & Korsching, S. I. Positive Darwinian selection and the birth of an olfactory receptor clade in teleosts. Proc Natl Acad Sci USA 106:4313–4318 (2009).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Niimura, Y. & Nei, M. Evolution of olfactory receptor genes in the human genome. Proc Natl Acad Sci USA 100:12235–12240 (2003).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Lee, A. C., Tian, H., Grosmaitre, X. & Ma, M. Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice. Chem Senses 34:695–703 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  22. Murphy, C. et al. Prevalence of olfactory impairment in older adults. JAMA 288:2307–2312 (2002).

    Article  PubMed  Google Scholar 

  23. Garcia-Esparcia, P. et al. Functional genomics reveals dysregulation of cortical olfactory receptors in Parkinson disease: novel putative chemoreceptors in the human brain. J Neuropathol Exp Neurol 72:524–539 (2013).

    Article  CAS  PubMed  Google Scholar 

  24. Choi, M. R. et al. Ethanol-induced small heat shock protein genes in the differentiation of mouse embryonic neural stem cells. Arch Toxicol 85:293–304 (2011).

    Article  CAS  PubMed  Google Scholar 

  25. Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57 (2009).

    Article  CAS  Google Scholar 

  26. Baik, S. Y. et al. Fluoxetine-induced up-regulation of 14-3-3zeta and tryptophan hydroxylase levels in RBL-2H3 cells. Neurosci Lett 374:53–57 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Life Sciences, Hanyang University, 1271 Sa-dong, Ansan, Korea

    Chanchal Mandal, Kyoung Hwa Jung & Young Gyu Chai

  2. Institute of Natural Science and Technology, Hanyang University, 1271 Sa-dong, Ansan, Korea

    Kyoung Hwa Jung

  3. Department of Nanobiotechnology, Hanyang University, Seoul, Korea

    Young Gyu Chai

Authors
  1. Chanchal Mandal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoung Hwa Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young Gyu Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kyoung Hwa Jung or Young Gyu Chai.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mandal, C., Jung, K.H. & Chai, Y.G. Ethanol toxicity affects olfactory receptor genes in forebrain of fetal mice. Mol. Cell. Toxicol. 11, 55–60 (2015). https://doi.org/10.1007/s13273-015-0007-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-015-0007-5

Keywords

  • Prenatal alcohol exposure
  • Binge alcohol
  • Microarray
  • Olfactory transduction
  • Odor detection