个体和联合暴露于多环芳烃（PAH）和邻苯二甲酸酯（PAE）代谢物与妊娠早期母体雌二醇水平的关系：一项横断面研究

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-10-11 DOI:10.1016/j.reprotox.2025.109081

Lin Tao , Jing Yang , Zhongmei Hu , Dengqing Liao , Shimin Xiong , LuLu Dai , Yuan-zhong Zhou , Xubo Shen

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引用次数: 0

摘要

多环芳烃（PAHs）和邻苯二甲酸酯（PAEs）具有内分泌干扰作用；然而，关于孕妇同时接触这两类污染物与性激素水平之间关系的研究仍然有限。为了解决这一差距，我们从遵义出生队列（ZBC）中纳入了454名早孕妇女，并使用线性混合效应模型（LMM）、贝叶斯核机回归（BKMR）和限制性三次样条（RCS）模型来研究早孕个体和联合暴露于多环芳烃和PAEs与母体雌二醇水平之间的关系。LMM结果显示，PAH代谢物与雌二醇之间没有显著相关性，但PAE代谢物与雌二醇之间存在显著相关性——主要由邻苯二甲酸单异丁酯（MIBP）和邻苯二甲酸单丁酯（MBP）推动，相应的β值（95%置信区间[ci]）分别为-534.77（-761.17,-308.37）和473.19（233.80,712.58）。BKMR分析显示，单独暴露于多环芳烃代谢物与雌二醇呈负相关，主要涉及4-羟基菲（4-OHPH）和1-羟基芘（1-OHPYR）。单独暴露于PAE代谢物也与雌二醇呈负相关，主要由邻苯二甲酸一乙酯（MEP）、MIBP和MBP驱动。同时暴露于PAE和PAH代谢物与雌二醇呈负相关，主要影响因素包括2-羟基芴（2-OHFLU）、MiBP、MBP、邻苯二甲酸单（2-乙基己基）酯（MEHP）和邻苯二甲酸单（2-乙基-5-氧己基）酯（MEOHP）。RCS结果显示，2-OHFLU与雌二醇呈倒u型关系（F=2.8， P=0.019）， MIBP与雌二醇呈非线性负相关（F=3.3， P=0.002）， MEOHP与雌二醇呈倒u型关系（F=4.4， P=0.005）。总的来说，这些发现表明，怀孕早期单独或联合暴露于多环芳烃和多环芳烃与孕妇的雌二醇水平有关，并有证据表明暴露-反应关系。建议在妊娠早期减少接触多环芳烃和多环芳烃代谢物，以进一步保障母婴健康。

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Association of individual and combined exposure to polycyclic aromatic hydrocarbon (PAH) and phthalate (PAE) metabolites with maternal estradiol levels in early pregnancy: A cross-sectional study

Polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) exert endocrine-disrupting effects; however, research investigating the relationship between co-exposure to these two classes of pollutants and sex hormone levels in pregnant women remains limited. To address this gap, we enrolled 454 women in early pregnancy from the Zunyi Birth Cohort (ZBC) and used linear mixed-effects models (LMM), Bayesian kernel machine regression (BKMR), and restricted cubic spline (RCS) models to examine associations between early-pregnancy both individual and combined exposur to PAHs and PAEs and maternal estradiol levels. LMM results revealed no significant associations between PAH metabolites and estradiol, but significant associations between PAE metabolites and estradiol—primarily driven by monoisobutyl phthalate (MIBP) and monobutyl phthalate (MBP), with corresponding β values (95 % confidence intervals [CIs]) of −534.77 (-761.17, −308.37) and 473.19 (233.80, 712.58), respectively. BKMR analyses showed that exposure to PAH metabolites alone was negatively associated with estradiol, primarily involving 4-hydroxyphenanthrene (4-OHPH) and 1-hydroxypyrene (1-OHPYR). Exposure to PAE metabolites alone was also negatively associated with estradiol, driven mainly by monoethyl phthalate (MEP), MIBP, and MBP. Concurrent exposure to PAE and PAH metabolites was negatively associated with estradiol, with key contributors including 2-hydroxyfluorene (2-OHFLU), MiBP, MBP, mono(2-ethylhexyl) phthalate (MEHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). RCS results demonstrated an inverted U-shaped relationship between 2-OHFLU and estradiol (F=2.8, P = 0.019), a non-linear negative association between MIBP and estradiol (F=3.3, P = 0.002), and an inverted U-shaped relationship between MEOHP and estradiol (F=4.4, P = 0.005). Collectively, these findings indicate that both individual and combined exposure to PAHs and PAEs in early pregnancy is associated with estradiol levels in pregnant women, with evidence of exposure-response relationships. Reducing exposure to PAH and PAE metabolites in early pregnancy is recommended to further safeguard maternal and fetal health.

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.