Autism spectrum disorders, endocrine disrupting compounds, and heavy metals in amniotic fluid: a case-control study
Autism spectrum disorders, endocrine disrupting compounds, and heavy metals in amniotic fluid: a case-control study
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DOI：
10.1186/s13229-018-0253-1
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发表时间：
2019-01-09
期刊：
影响因子：
6.2
通讯作者：
Bonefeld-Jorgensen, Eva C.
中科院分区：
文献类型：
--
作者：
Long, Manhai;Ghisari, Mandana;Bonefeld-Jorgensen, Eva C.
背景证据表明，一些非遗传因素（例如暴露于环境污染物）与自闭症谱系障碍（ASD）等神经发育障碍有关。研究报告称，内分泌干扰化合物（EDC），包括多氯联苯、有机氯农药、全氟烷基物质（PFAS）和一些金属，对胎儿神经发育有不利影响。本研究的目的是测量羊水中 EDC 和金属的水平以及 AF 诱导的受体反式活性，并调查产前接触 EDC 和重金属与 ASD 风险之间可能存在的联系。 方法在这项病例对照研究中，我们纳入了 75 例 ASD 病例和 135 例频率匹配对照的 AF 样本，并测量了内源性激素、PFAS 和包括重金属在内的元素的水平。还测定了内源激素和 EDC 对雌激素 (ER)、雄激素 (AR)、芳烃 (AhR) 受体和甲状腺激素样活性的综合作用，并表示为受体配体当量。我们使用非条件逻辑回归分析评估了化学物质、性激素和受体活性的 AF 水平与 ASD 风险的关联。为了控制多重比较，使用错误发现率 (FDR)，并将 q 值小于 0.25 指定为统计显着性。结果 AF 样品中可检测到 PFAS 和金属。 ASD 病例的 AF PFAS 水平显着低于对照组，全氟辛烷磺酸 (PFOS) 的调整后比值比 (OR) 为 0.410（95% CI 0.174，0.967；p=0.042；FDR q（值）=0.437）。主要成分，包括 PFAS 同系物、铜、铁和雌激素活性，与 ASD 风险显着负相关（调整后 OR=0.100；95% CI 0.016, 0.630；p=0.014；FDR q（值）=0.098）。 AF 中的睾酮水平与 ASD 风险弱相关（调整后 OR=1.002；95% CI 1.000，1.004；p=0.05)。然而，经过多重比较校正后，相关性并不显着（FDR q(值)=0.437）。未观察到 AF 诱导的受体反式活性与 ASD 风险之间存在显着关联。合并雄激素活性与合并雌激素活性之比的调整后 OR 为 2.176 (95% CI 0.115, 41.153)。结论 AF 中存在 PFAS 和重金属表明它们可以穿过胎盘。 AF 和 ASD 风险中 PFAS 同系物水平之间的负相关可能与 PFAS 的雌激素活性和抗雄激素活性较弱有关。观察到的联合雄激素作用与联合雌激素作用的比率与 ASD 风险之间的正相关趋势需要进一步研究，以探讨 EDC 与内源性激素是否一起在 ASD 的发生中发挥作用。
BackgroundEvidence has indicated that some non-inherited factors such as exposure to environmental pollutants are associated with neurodevelopment disorders like autism spectrum disorder (ASD). Studies report that endocrine disrupting compounds (EDCs), including polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances (PFAS), and some metals, have adverse effects on the fetal neurodevelopment. The aim of this study was to measure the amniotic fluid (AF) levels of EDCs and metals as well as the receptor transactivities induced by AF and investigate the possible link between prenatal exposure to EDCs and heavy metals and ASD risk.MethodsIn this case-control study, we included AF samples of 75 ASD cases and 135 frequency-matched controls and measured the levels of the endogenous sex hormones, PFAS, and elements including heavy metals. The combined effect of endogenous hormones and EDCs on the receptor of estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and thyroid hormone-like activity were also determined and expressed as receptor ligand equivalents. We assessed the associations of AF levels of chemicals, sex hormones, and receptor activities with ASD risk using unconditional logistical regression analyses. To control for multiple comparisons, the false discovery rate (FDR) was used and q values less than 0.25 were designated as statistical significance.ResultsPFAS and metals were detectable in AF samples. The ASD cases had significantly lower AF levels of PFAS than controls, and the adjusted odds ratio (OR) was 0.410 (95% CI 0.174, 0.967; p=0.042; FDR q(value)=0.437) for perfluorooctane sulfonate (PFOS). The principal component, including PFAS congeners, copper, iron, and estrogenic activity, was significantly inversely associated with ASD risk (adjusted OR=0.100; 95% CI 0.016, 0.630; p=0.014; FDR q(value)=0.098).Testosterone level in AF weakly associated with ASD risk (adjusted OR=1.002; 95% CI 1.000, 1.004; p=0.05). However, after multiple comparison correction, the association was not significant (FDR q(value)=0.437). No significant associations between AF-induced receptor transactivities and ASD risk were observed. The adjusted OR was 2.176 (95%CI 0.115, 41.153) for the ratio of the combined androgenic activity to combined estrogenic activity.ConclusionsThe presence of PFAS and heavy metals in AF indicates that they can cross the placenta. The inverse association between levels of PFAS congeners in AF and ASD risk might relate to the weak estrogenic activities and anti-androgenic activities of PFAS.The observed tendency of positive association between the ratio of combined androgenic effect to the combined estrogenic effect and ASD risk needs further studies to explore whether EDCs together with endogenous hormones play a role in the development of ASD.