Song Ge, Wang Rui, Cui Yi, Hao Chan Juan, Xia Hong-Fei, Ma Xu
Reproductive and Genetic Center of National Research Institute for Family Planning, Da Hui Si Road, Beijing 100081, China.
Department of Blood Transfusion, First medical center, Chinese People's Liberation Army General Hospital, Fu Xing Road, Beijing 100853, China.
Toxicol Res (Camb). 2020 Sep 4;9(5):622-631. doi: 10.1093/toxres/tfaa058. eCollection 2020 Sep.
Diethylhexyl phthalate (DEHP) is known as a persistent environmental pollutant. However, the possible effects of DEHP on human neural tube defects (NTDs) remain elusive. We set out to investigate the exposure of DEHP in human and explore the association of DEHP and NTDs. The level of DEHP in maternal urine was measured and analyzed by GC-MS. To further validate the results in human NTDs, chick embryos were used as animal models. Viability, reactive oxygen species (ROS) level, oxidative stress indicators and apoptosis were detected in DEHP-treated chick embryos. Our research revealed that the detection ratio of positive DEHP and its metabolites in maternal urine were observed dramatically higher in NTDs population than that in normal controls ( 0.01, 0.05, respectively). Moreover, DEHP treatment (10 M) led to developmental toxicity in chick embryos via accelerating oxidative stress response and cell apoptosis, and changing the level of oxidative stress-related indicators. Moreover, high dose choline (100 μg/μl) could partially restrain the toxicity effects induced by DEHP. Our data collectively imply that the incidence of NTDs may closely associate with DEHP exposure, which disturbs the development of neural tubes by enhancing oxidative stress.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种持久性环境污染物。然而，DEHP对人类神经管缺陷（NTDs）的潜在影响仍不清楚。我们着手研究人类中DEHP的暴露情况，并探索DEHP与NTDs之间的关联。通过气相色谱-质谱联用仪（GC-MS）测量和分析孕妇尿液中DEHP的水平。为了进一步验证人类NTDs的研究结果，以鸡胚作为动物模型。检测DEHP处理的鸡胚的活力、活性氧（ROS）水平、氧化应激指标和细胞凋亡情况。我们的研究表明，NTDs人群孕妇尿液中DEHP及其代谢产物的阳性检出率显著高于正常对照组（分别为P<0.01，P<0.05）。此外，DEHP处理（10μM）通过加速氧化应激反应和细胞凋亡以及改变氧化应激相关指标的水平，导致鸡胚发育毒性。此外，高剂量胆碱（100μg/μl）可部分抑制DEHP诱导的毒性作用。我们的数据共同表明，NTDs的发生率可能与DEHP暴露密切相关，DEHP通过增强氧化应激干扰神经管的发育。
