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Vinyl Chloride Monomer (VCM) Induces High Occurrence of Neural Tube Defects in Embryonic Mouse Brain During Neurulation

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Abstract

The aim of this study was to explore the direct embryonic teratogenicity of vinyl chloride monomer (VCM), especially the toxic effects on the early development of the nervous system and its underlying mechanisms. Pregnant mice at embryonic day 6.5 (E6.5) were injected with different doses of VCM (200, 400 and 600 mg/kg) and embryos were harvested at E10.5. Our results showed that doses higher than 400 mg/kg of VCM increased the incidence of malformed embryos, especially the neural tube defects (NTDs). In addition, high-dose of VCM decreased mitotic figure counts in the neuroepithelium and enhanced the percentage of cells in G0/G1 phase, while they were reduced in S phase. The more VCM was injected into mice, the fewer positive PCNA cells were seen and the more positive TUNEL cells were observed in the neuroepithelium. Moreover, significant increases in the levels of caspase-3 protein were observed in NTD embryos. Our results demonstrate that during early pregnancy, exposure to doses higher than 400 mg/kg of VCM increases the incidence of malformations and particularly the rate of NTDs. High-dose of VCM inhibits the proliferation of neural cells and induces cell apoptosis, leading to an imbalance in the ratio of proliferation and apoptosis. Meanwhile, the apoptosis of neuroepithelial cells might be accelerated by the activation of the caspase-3 pathway, and it might be a reason for NTDs.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (31271467), Natural Science Foundation Project of CQ CSTC (2010BB5031), and The Innovation Foundation of the Third Military Medical University, China (2011XHG01).

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We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Histology and Embryology, Third Military Medical University, Gaotanyan St 30#, Shapingba District, Chongqing, 400038, People’s Republic of China

    Hongyu Quan, Teng Ma, Xianxian Zhao, Baixiong Zhao, Yunlai Liu & Hongli Li

  2. Battalion 19 of the Department of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Hongyu Quan

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  1. Hongyu Quan
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  2. Teng Ma
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Correspondence to Hongli Li.

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Quan, H., Ma, T., Zhao, X. et al. Vinyl Chloride Monomer (VCM) Induces High Occurrence of Neural Tube Defects in Embryonic Mouse Brain During Neurulation. Cell Mol Neurobiol 34, 619–630 (2014). https://doi.org/10.1007/s10571-014-0049-6

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