Display options
Share it on

Front Neurosci. 2020 Nov 25;14:591196. doi: 10.3389/fnins.2020.591196. eCollection 2020.

Anticonvulsants and Chromatin-Genes Expression: A Systems Biology Investigation.

Frontiers in neuroscience

Thayne Woycinck Kowalski, Julia do Amaral Gomes, Mariléa Furtado Feira, Ágata de Vargas Dupont, Mariana Recamonde-Mendoza, Fernanda Sales Luiz Vianna

Affiliations

  1. Postgraduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
  2. Laboratory of Immunobiology and Immunogenetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
  3. National Institute of Population Medical Genetics (INAGEMP), Porto Alegre, Brazil.
  4. Genomic Medicine Laboratory, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
  5. National System of Information on Teratogenic Agents (SIAT), Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
  6. Centro Universitário CESUCA, Cachoeirinha, Brazil.
  7. Bioinformatics Core, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
  8. Institute of Informatics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

PMID: 33328862 PMCID: PMC7732676 DOI: 10.3389/fnins.2020.591196

Abstract

Embryofetal development is a critical process that needs a strict epigenetic control, however, perturbations in this balance might lead to the occurrence of congenital anomalies. It is known that anticonvulsants potentially affect epigenetics-related genes, however, it is not comprehended whether this unbalance could explain the anticonvulsants-induced fetal syndromes. In the present study, we aimed to evaluate the expression of epigenetics-related genes in valproic acid, carbamazepine, or phenytoin exposure. We selected these three anticonvulsants exposure assays, which used murine or human embryonic stem-cells and were publicly available in genomic databases. We performed a differential gene expression (DGE) and weighted gene co-expression network analysis (WGCNA), focusing on epigenetics-related genes. Few epigenetics genes were differentially expressed in the anticonvulsants' exposure, however, the WGCNA strategy demonstrated a high enrichment of chromatin remodeling genes for the three drugs. We also identified an association of 46 genes related to Fetal Valproate Syndrome, containing

Copyright © 2020 Kowalski, Gomes, Feira, Dupont, Recamonde-Mendoza and Vianna.

Keywords: WGCNA; antiepileptics; epigenetics; fetal hydantoin syndrome; fetal valproate syndrome; phenytoin; teratogen; valproic acid

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Epigenetics Chromatin. 2019 Jan 22;12(1):9 - PubMed
  2. Anim Reprod Sci. 2014 Sep;149(1-2):30-8 - PubMed
  3. Annu Rev Biochem. 2009;78:273-304 - PubMed
  4. Integr Biol (Camb). 2018 Sep 17;10(9):491-501 - PubMed
  5. Toxicol Sci. 2011 Jan;119(1):126-34 - PubMed
  6. Brief Funct Genomic Proteomic. 2008 Jul;7(4):239-48 - PubMed
  7. Cold Spring Harb Symp Quant Biol. 2016;81:53-60 - PubMed
  8. Reprod Toxicol. 2006 Aug;22(2):214-26 - PubMed
  9. BMC Bioinformatics. 2008 Dec 29;9:559 - PubMed
  10. Genome Res. 2015 Oct;25(10):1473-81 - PubMed
  11. Br J Clin Pharmacol. 2009 Dec;68(6):956-62 - PubMed
  12. Reprod Toxicol. 2019 Sep;88:67-75 - PubMed
  13. Curr Opin Neurol. 2019 Apr;32(2):246-252 - PubMed
  14. Am J Obstet Gynecol. 2011 Jul;205(1):51.e1-8 - PubMed
  15. Nat Rev Genet. 2015 Mar;16(3):146-58 - PubMed
  16. Ann Clin Lab Sci. 2010 Spring;40(2):99-114 - PubMed
  17. Nature. 2014 Apr 10;508(7495):263-8 - PubMed
  18. Exp Neurol. 2018 Jan;299(Pt A):217-227 - PubMed
  19. Carcinogenesis. 2007 Mar;28(3):560-71 - PubMed
  20. Nat Rev Mol Cell Biol. 2018 Jan;19(1):59-70 - PubMed
  21. Curr Pharm Des. 2013;19(28):5043-50 - PubMed
  22. Brain Sci. 2020 Aug 12;10(8): - PubMed
  23. Alcohol Clin Exp Res. 2016 Aug;40(8):1594-602 - PubMed
  24. Eur J Obstet Gynecol Reprod Biol. 2004 Nov 10;117(1):10-9 - PubMed
  25. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D433-7 - PubMed
  26. Genes (Basel). 2017 May 24;8(6): - PubMed
  27. Genet Mol Biol. 2017 Apr-Jun;40(2):387-397 - PubMed
  28. Toxicol Appl Pharmacol. 2012 Aug 1;262(3):330-40 - PubMed
  29. Toxicol Sci. 2015 Aug;146(2):311-20 - PubMed
  30. Nat Cell Biol. 2018 Aug;20(8):878-887 - PubMed
  31. Eur J Med Genet. 2017 Jan;60(1):22-31 - PubMed
  32. Arch Toxicol. 2020 Feb;94(2):631-645 - PubMed
  33. Toxicol Sci. 2013 Mar;132(1):118-30 - PubMed
  34. Trends Biochem Sci. 2014 Jun;39(6):289-98 - PubMed
  35. Nat Rev Mol Cell Biol. 2019 Oct;20(10):625-641 - PubMed
  36. Toxicol Appl Pharmacol. 2010 Nov 1;248(3):201-9 - PubMed
  37. Pharmacol Rev. 2019 Oct;71(4):520-538 - PubMed
  38. J Med Genet. 2010 Feb;47(2):73-80 - PubMed

Publication Types