Abstract

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 (P < 0.01, P < 0.05, respectively). Moreover, DEHP treatment (10⁻⁶ 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.

中文翻译：

---

邻苯二甲酸二乙基己酯通过鸡胚胎模型中的氧化应激反应诱导致畸作用

摘要

邻苯二甲酸二乙基己酯 (DEHP) 是一种持久性环境污染物。然而，DEHP 对人类神经管缺陷 (NTD) 的可能影响仍然难以捉摸。我们着手调查人类 DEHP 的暴露情况，并探讨 DEHP 与 NTD 的关联。通过GC-MS测量和分析母体尿液中DEHP的水平。为了进一步验证人类 NTD 的结果，使用鸡胚作为动物模型。在 DEHP 处理的鸡胚中检测到活力、活性氧 (ROS) 水平、氧化应激指标和细胞凋亡。我们的研究表明，NTDs人群母体尿液中DEHP阳性及其代谢物的检出率显着高于正常对照组（P <  0.01，P < 0.05，分别）。此外，DEHP 处理（10 ^-6  M）通过加速氧化应激反应和细胞凋亡，并改变氧化应激相关指标的水平，导致鸡胚胎发育毒性。此外，高剂量胆碱 (100 μg/μl) 可以部分抑制 DEHP 引起的毒性作用。我们的数据共同暗示 NTD 的发生率可能与 DEHP 暴露密切相关，DEHP 会通过增强氧化应激来干扰神经管的发育。