Choline, not folate, can attenuate the teratogenic effects ofdibutyl phthalate (DBP) during early chick embryo development

  • Rui Wang
  • Da-Guang Sun
  • Ge Song
  • Chun Yi Guan
  • Yi Cui
  • Xu MaEmail author
  • Hong-Fei XiaEmail author
Research Article


Dibutyl phthalate (DBP), a persistent environmental pollutant, can induce neural tube abnormal development in animals. The possible effects of DBP exposure on human neural tube defects (NTDs) remain elusive. In this study, the distribution of DBP in the body fluid of human NTDs was detected by GC-MS. Then, chick embryos were used to investigate the effects of DBP on early embryonic development. Oxidative stress indicators in chick embryos and the body fluid of human NTDs were detected by ELISA. The cell apoptosis and total reactive oxygen species (ROS) level in chick embryos were detected by whole-mount TUNEL and oxidized DCFDA, respectively. The study found that the detection ratio of positive DBP and its metabolites in maternal urine was higher in the NTD population than that in normal controls. 8-hydroxy-2 deoxyguanosine (8-OHDG) and malondialdehyde (MDA) were evidently upregulated and superoxide dismutase (SOD) was observably downregulated in amniotic fluid and urine. Animal experiments indicated that DBP treatment induced developmental toxicity in chick embryos by enhancing the levels of oxidative stress and cell apoptosis. MDA was increased and SOD was decreased in DBP-treated embryos. Interestingly, the supplement of high-dose choline (100 μg/μL), not folic acid, could partially restore the teratogenic effects of DBP. Our data collectively suggest that the incidence of NTDs is closely associated with DBP exposure. This study may provide new insight for NTD prevention.


Dibutyl phthalate Human neural tube defects Oxidative stress Body fluid Chick embryo Choline 


Funding information

This work was financially supported by grants from The National Key Research and Development Program of China (2016YFC1000307), CAMS Innovation Fund for Medical Sciences (CIFMS, 2018-I2M-1-004), and the Open Grant from Chongqing Key Laboratory of Birth Defects and Reproductive Health (No. 1111).

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Supplementary material

11356_2019_6087_MOESM1_ESM.doc (161 kb)
ESM 1 (DOC 161 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Blood Transfusion, First medical centerChinese People’s Liberation Army General HospitalBeijingChina
  2. 2.Reproductive and Genetic Center of National Research Institute for Family PlanningBeijingChina
  3. 3.Chongqing Key Laboratory of Birth Defects and Reproductive HealthChongqingChina
  4. 4.Graduate SchoolPeking Union Medical CollegeBeijingChina

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