Tao Lin, Xiong Shimin, Dai Lulu, Liao Dengqing, Zhou Yuan-Zhong, Shen Xubo
School of Public Health, Zunyi Medical University, Zunyi, 563000, Guizhou Province, China.
Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes, Zunyi, 563000, Guizhou Province, China.
Arch Toxicol. 2025 Sep 2. doi: 10.1007/s00204-025-04172-3.
Phthalates (PAEs) are well-recognized endocrine-disrupting compounds. Despite their established status as such, the association between maternal exposure to PAEs during pregnancy and the levels of maternal thyroid hormones remains a subject of considerable debate. To shed light on this contentious issue, we conducted an investigation involving 1,156 pregnant women from the Zunyi birth cohort. The aim was to elucidate the relationship between urinary metabolites of PAEs and serum thyroid hormones during the gestational period. In this study, we employed a linear mixed-effects model (LMM) to assess the correlation between PAE metabolites and thyroid hormones. Additionally, restricted cubic spline (RCS) analysis was utilized to explore the dose-response relationship between these PAE metabolites and thyroid hormones. Furthermore, Bayesian kernel machine regression (BKMR) was applied to determine the potential overall effects and to uncover any non-linear relationships that might exist. Our results revealed that several PAE metabolites, namely, monomethyl phthalate (MMP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MIBP), mono(2-ethyl-5-oxohexyl) phthalate (MOP), and monobenzyl phthalate (MBZP), were associated with correlations involving total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4). Subsequently, the restricted cubic spline (RCS) analyses demonstrated a clear dose-response relationship between the PAE metabolites and maternal thyroid hormones, with MEHP, MBZP, MIBP, and MBZP emerging as the major contributors to this relationship. Finally, the BKMR model indicated a non-linear relationship, specifically an inverted U-shaped relationship, between maternal exposure to PAEs during pregnancy and the levels of TT4, FT3, and FT4. Collectively, our findings strongly suggest that exposure to PAEs during pregnancy has a detrimental impact on the secretion of maternal thyroid hormones. To safeguard the health of both the mother and the fetus, it is advisable to minimize exposure to phthalates during pregnancy and to monitor any alterations in thyroid hormone levels closely.
邻苯二甲酸酯（PAEs）是公认的内分泌干扰化合物。尽管它们已确立了这样的地位，但孕期母亲接触PAEs与母亲甲状腺激素水平之间的关联仍是一个备受争议的话题。为了阐明这个有争议的问题，我们对来自遵义出生队列的1156名孕妇进行了一项调查。目的是阐明孕期PAEs的尿代谢物与血清甲状腺激素之间的关系。在本研究中，我们采用线性混合效应模型（LMM）来评估PAE代谢物与甲状腺激素之间的相关性。此外，使用受限立方样条（RCS）分析来探索这些PAE代谢物与甲状腺激素之间的剂量反应关系。此外，应用贝叶斯核机器回归（BKMR）来确定潜在的总体效应，并揭示可能存在的任何非线性关系。我们的结果显示，几种PAE代谢物，即单甲基邻苯二甲酸酯（MMP）、单（2-乙基己基）邻苯二甲酸酯（MEHP）、单（2-乙基-5-羧基戊基）邻苯二甲酸酯（MECPP）、单异丁基邻苯二甲酸酯（MIBP）、单（2-乙基-5-氧代己基）邻苯二甲酸酯（MOP）和单苄基邻苯二甲酸酯（MBZP），与涉及总甲状腺素（TT4）、游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）的相关性有关。随后，受限立方样条（RCS）分析表明PAE代谢物与母亲甲状腺激素之间存在明显的剂量反应关系，MEHP、MBZP、MIBP和MBZP是这种关系的主要促成因素。最后，BKMR模型表明孕期母亲接触PAEs与TT4、FT3和FT4水平之间存在非线性关系，具体为倒U形关系。总体而言，我们的研究结果强烈表明，孕期接触PAEs会对母亲甲状腺激素的分泌产生不利影响。为了保障母亲和胎儿的健康，建议在孕期尽量减少接触邻苯二甲酸酯，并密切监测甲状腺激素水平的任何变化。
