Department of Blood Transfusion, First medical center, Chinese People's Liberation Army General Hospital, Beijing, China.
Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.
Environ Sci Pollut Res Int. 2019 Oct;26(29):29763-29779. doi: 10.1007/s11356-019-06087-w. Epub 2019 Aug 12.
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.
邻苯二甲酸二丁酯（DBP）是一种持久性环境污染物，可诱导动物神经管发育异常。DBP 暴露对人类神经管缺陷（NTDs）的可能影响仍不清楚。在这项研究中，通过 GC-MS 检测了 DBP 在人 NTD 体液中的分布。然后，使用鸡胚研究 DBP 对早期胚胎发育的影响。通过 ELISA 检测鸡胚和人 NTD 体液中的氧化应激指标。通过全胚胎 TUNEL 和氧化型 DCFDA 分别检测鸡胚中的细胞凋亡和总活性氧（ROS）水平。研究发现，NTD 人群中母体尿液中 DBP 及其代谢物的阳性检出率高于正常对照组。羊水中 8-羟基-2 脱氧鸟苷（8-OHDG）和丙二醛（MDA）明显上调，超氧化物歧化酶（SOD）明显下调。动物实验表明，DBP 通过增强氧化应激和细胞凋亡水平，诱导鸡胚发育毒性。DBP 处理的胚胎中 MDA 增加，SOD 减少。有趣的是，高剂量胆碱（100μg/μL）而非叶酸的补充可以部分恢复 DBP 的致畸作用。我们的数据表明，NTD 的发生率与 DBP 暴露密切相关。这项研究可能为 NTD 的预防提供新的思路。
