Centre for Arctic Health & Molecular Epidemiology, Department of Public Health, Aarhus University, Denmark.
Research unit for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
Sci Total Environ. 2023 Nov 1;897:165286. doi: 10.1016/j.scitotenv.2023.165286. Epub 2023 Jul 6.
Human exposure to lipophilic persistent organic pollutants (lipPOP) is ubiquitous and life-long, beginning during foetal development. Exposure to lipPOP elicits a number of species and tissue specific responses including dioxin-like activity which involve the activation of aryl hydrocarbon receptor (AhR). This study aims i) to describe the combined dioxin-like activity in serum from Danish pregnant women collected during 2011-2013; ii) to assess the association between maternal serum dioxin-like activity, gestational age at birth and foetal growth indices. The serum lipPOP fraction was extracted using Solid Phase Extraction and cleaned-up on Supelco multi-layer silica and florisil columns. The combined dioxin-like activity of the extract was determined using the AhR reporter gene bioassay, expressed as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent (TEQ) [AhR-TEQ (pg/g lipid)]. The associations of AhR-TEQ and foetal growth indices (birth weight, birth length and head circumference) and gestational age were assessed by linear regression models. We detected AhR-TEQ in 93.9 % of maternal first trimester serum samples, with a median level of 185 pg/g lipid. Each ln-unit increase in AhR-TEQ was associated with an increase in birth weight of 36 g (95 % CI: 5; 68), birth length of 0.2 cm (95 % CI: 0.01; 0.3) and pregnancy duration of 1 day (95 % CI: 0; 1.5). In women who never smoked, higher AhR-TEQ values were associated with higher birth weight and longer duration of gestation, while in smokers the association was the opposite. Mediation analyses suggested that gestational age may mediate the association of AhR-TEQ with foetal growth indices. We conclude that AhR activating substances are present in the bloodstream of almost all pregnant women in Denmark and the AhR-TEQ level was around four times higher than previously reported. The AhR-TEQ was associated with slightly longer gestational duration and thereby higher birth weight and birth length.
人体接触亲脂性持久性有机污染物（lipPOP）是普遍存在且终生的，从胎儿发育时期就开始了。接触 lipPOP 会引起许多种组织特异性反应，包括类二恶英活性，这涉及到芳香烃受体（AhR）的激活。本研究旨在：i）描述 2011-2013 年丹麦孕妇血清中的联合类二恶英活性；ii）评估母体血清中二恶英样活性、出生时的胎龄和胎儿生长指数之间的关联。使用固相萃取法提取血清中的 lipPOP 馏分，并用 Supelco 多层硅胶和 florisil 柱进行净化。使用 AhR 报告基因生物测定法测定提取物的联合类二恶英活性，用 2,3,7,8-四氯二苯并对二恶英（TCDD）毒性当量（TEQ）[AhR-TEQ（pg/g 脂质）]表示。通过线性回归模型评估 AhR-TEQ 与胎儿生长指数（出生体重、出生体长和头围）和胎龄的相关性。我们检测了 93.9%的孕妇孕早期血清样本中的 AhR-TEQ，中位数水平为 185pg/g 脂质。AhR-TEQ 每增加一个自然对数单位，出生体重就会增加 36g（95%CI：5；68），出生体长增加 0.2cm（95%CI：0.01；0.3），胎龄增加 1 天（95%CI：0；1.5）。在从未吸烟的女性中，AhR-TEQ 值较高与出生体重较高和妊娠持续时间较长有关，而在吸烟者中则相反。中介分析表明，胎龄可能介导 AhR-TEQ 与胎儿生长指数的关联。我们的结论是，几乎所有丹麦孕妇的血液中都存在激活 AhR 的物质，AhR-TEQ 水平比之前报道的高出四倍左右。AhR-TEQ 与胎龄稍长有关，从而与出生体重和出生体长较高有关。
