| 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 extra-embryonic vascular area, accompanied by a significantly increased incidence of the failed closure of the caudal end of the neural tube. CHO, at low dose (25μg/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 (25μg/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 (50μg/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. Phthalate Acid Esters (PAEs) as a class of persistent environmental pollutants, whereby inducing congenital malformations such as neural tube defects (NTDs) in animals.Apoptosis plays an important role in the process of neural tube, there is closely relationship between apoptosis and oxidative stress, there is a certain extent among oxidative stress-apoptosis and neural tube defects. This suggested us that the occurrence of neural tube defects not only with the lack of relevant folic acid, but also with oxidative stress and apoptosis.Therefore, the molecular mechanism of neurodevelopmental toxicity of PAEs and the induction of neural tube defects may be needs further study. In this study, we first detected the distribution of PAEs and oxidative stress-related indicators (SOD, MDA, GSH and 8-OHdG) in the NTD population, then we used chick embryos as animal model to investigate the effects of PAEs in early embryonic development of the nervous system, and we do the recovery experiment by nutritional supplements, to seek to nutrients which can antagonize toxic damage caused PAEs, to investigate the molecular mechanism of nutrient antagonism of embryo toxicity caused by PAEs. Our study shows that the incidence of neural tube defects is closely related to BBP/DEHP/DBP and its metabolites in maternal body and oxidative stress; BBP/DEHP/DBP induced toxicity in chick embryo by oxidative stress, however, the supplementary of CHO (100μg/μL) could partially restore its teratogenic effects. Taken together, these findings suggest that low dose CHO could protect chick embryos from PAEs by increasing the activity of antioxidant enzymes SOD and inhibiting the occurrence of oxidative stress. |
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