Department of Growth and Reproduction and International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
Department of Growth and Reproduction and International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
Environ Res. 2020 May;184:109231. doi: 10.1016/j.envres.2020.109231. Epub 2020 Feb 7.
Exposure to some phthalate diesters has been associated with adverse reproductive health outcomes in both rodents and humans indicative of anti-androgenic effects. Exposure during sensitive periods of development, such as prenatally, is of particular concern.
We wished to investigate whether phthalate metabolites measured in maternal serum samples from historical birth cohorts can be used to assess prenatal exposure. Further, we aimed to study temporal and geographical trends in phthalate exposure across three different birth cohorts.
We compared phthalate metabolite levels in maternal serum samples from an Australian (1989-91) and a Danish (1997-2001) birth cohort with levels in serum and urine samples from a recent Danish birth cohort (2012-14). Samples were analysed for 32 phthalate metabolites from 15 phthalate diesters by isotope-diluted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Correlations between metabolites were tested by Spearman rank correlation test, and differences between the cohorts were tested by Mann-Whitney U test.
Overall, we observed large variations in serum phthalate metabolite levels between individuals. Secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) in serum were weakly to moderately and positively correlated to the levels measured in urine, and secondary metabolites of DEHP were also moderately to strongly and significantly correlated in serum. Correlations with mono-(2-ethyl-hexyl) phthalate (MEHP) and mono-iso-nonyl phthalate (MiNP), the two primary metabolites of DEHP and DiNP, were inconsistent, and we found indications of sample contamination. We observed some significant differences in phthalate metabolite levels between the three cohorts with generally higher levels in the older birth cohorts.
Based on comparison across two older birth cohorts and a recent cohort, our results support the concept that historical biobanked serum samples may be used for assessment of prenatal exposure to phthalates when using serum levels of the monoesters of the low-molecular weight (LMW) phthalates and the secondary metabolites of the high-molecular weight (HMW) phthalates. Serum phthalate measurements are, however, not suitable for human biomonitoring and should only be used to exploit historical samples from cohorts, where urine samples were not collected. Our findings suggest that phthalate exposure may have decreased over time from the early 1990s to the 2010s.
一些邻苯二甲酸酯的暴露与啮齿动物和人类的不良生殖健康结果有关，表明其具有抗雄激素作用。在发育敏感时期（如产前）的暴露尤其令人关注。
我们希望研究从历史出生队列的母体血清样本中测量的邻苯二甲酸酯代谢物是否可用于评估产前暴露。此外，我们旨在研究三个不同出生队列中邻苯二甲酸酯暴露的时间和地域趋势。
我们比较了澳大利亚（1989-91 年）和丹麦（1997-2001 年）出生队列的母体血清样本中的邻苯二甲酸酯代谢物水平与最近丹麦出生队列（2012-14 年）的血清和尿液样本中的水平。通过同位素稀释液相色谱-串联质谱法（LC-MS/MS）对来自 15 种邻苯二甲酸酯二酯的 32 种邻苯二甲酸酯代谢物进行了分析。通过 Spearman 秩相关检验测试代谢物之间的相关性，通过 Mann-Whitney U 检验测试队列之间的差异。
总体而言，我们观察到个体之间的血清邻苯二甲酸酯代谢物水平存在很大差异。DEHP 和 DiNP 的次级代谢物与尿液中测量的水平呈弱至中度正相关，DEHP 的次级代谢物在血清中也呈中度至强显著相关。与 DEHP 和 DiNP 的两种主要代谢物 MEHP 和 MiNP 的相关性不一致，并且我们发现了样品污染的迹象。我们观察到三个队列中邻苯二甲酸酯代谢物水平存在一些显著差异，一般来说，较旧的出生队列的水平较高。
基于对两个较旧的出生队列和一个最近的队列进行比较，我们的结果支持这样的概念，即当使用低分子量（LMW）邻苯二甲酸酯的单酯和高分子量（HMW）邻苯二甲酸酯的次级代谢物的血清水平时，历史生物库血清样本可用于评估产前邻苯二甲酸酯暴露。然而，血清邻苯二甲酸酯测量不适用于人体生物监测，只能用于开发未收集尿液样本的队列中的历史样本。我们的研究结果表明，从 20 世纪 90 年代初到 21 世纪 10 年代，邻苯二甲酸酯的暴露可能随时间减少。
