Effects of choline on sodium arsenite-induced neural tube defects in chick embryos

Food Chem Toxicol. 2012 Dec;50(12):4364-74. doi: 10.1016/j.fct.2012.08.023. Epub 2012 Aug 20.

Abstract

Arsenic passes through the placenta and accumulates in the neuroepithelium of embryo, whereby inducing congenital malformations such as neural tube defects (NTDs) in animals. Choline (CHO), a methyl-rich nutrient, functions as a methyl donor to participate in methyl group metabolism. Arsenic methylation has been regarded as a detoxification process and choline (CHO) is the major source of methyl-groups. However, whether CHO intake reverses the abnormal embryo development induced by sodium arsenite (SA) and the relationship between CHO intake and arsenite-induced NTDs are still unclear. In this study, we used chick embryos as animal model to investigate the effects of SA and CHO supplementation on the early development of nervous system. Our results showed that the administration of SA led to reduction in embryo viability, embryo body weight and extraembryonic vascular area, accompanied by a significantly increased incidence of the failed closure of the caudal end of the neural tube. CHO, at low dose (25 μg/μL), reversed the decrease in embryo viability and the increase in the failed closure of the caudal end of the neural tube, which were induced by SA. In addition, CHO (25 μg/μL) inhibited not only the SA-induced cell apoptosis by up-regulating Bcl-2 level, but also the global DNA methylation by increasing the expressions of DNMT1 and DNMT3a. However, less significant difference was found between the embryos co-treated with SA and CHO (50 μg/μL) and the ones treated with SA alone. Taken together, these findings suggest that low dose CHO could protect chick embryos from arsenite-induced NTDs by a possible mechanism related to the methyl metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Arsenites / toxicity*
  • Chick Embryo
  • Choline / pharmacology*
  • Cricetinae
  • DNA Methylation
  • Dose-Response Relationship, Drug
  • Embryonic Development / drug effects
  • Models, Animal
  • Neural Tube / drug effects
  • Neural Tube / pathology
  • Neural Tube Defects / chemically induced
  • Neural Tube Defects / pathology*
  • Sodium Compounds / toxicity*
  • Up-Regulation
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Arsenites
  • Sodium Compounds
  • bcl-2-Associated X Protein
  • sodium arsenite
  • Choline