Blaauwendraad Sophia M, Boxem Aline J, Gaillard Romy, Kahn Linda G, Lakuleswaran Mathusa, Sakhi Amrit Kaur, Bekkers Eline L, Mo Zixuan, Spadacini Larry, Thomsen Cathrine, Steegers Eric Ap, Mulders Annemarie Gmgj, Jaddoe Vincent Wv, Trasande Leonardo
The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands.
The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands.
Environ Res. 2025 Aug 1;278:121712. doi: 10.1016/j.envres.2025.121712. Epub 2025 Apr 29.
Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates might lead to adverse fertility and early pregnancy outcomes.
This study was embedded in the Generation R Next Study, a population-based cohort study from preconception onwards. Urinary phthalate and bisphenol concentrations were assessed in the preconception period (938 women), defined as the period in which couples were actively trying to conceive, and early pregnancy (1,366 women and 1,202 men, mean gestational age at sampling 8·6 weeks). Time to pregnancy and miscarriage were assessed using questionnaires and ultrasounds. Subfertility was defined as the inability to conceive within 12 months or need for assisted reproductive technologies.
Higher preconception urinary bisphenol S (BPS) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (mCOCH) concentrations in women were associated with longer time to pregnancy. Higher preconception mono-[(2-carboxymethyl)hexyl] phthalate, mono-2-ethyl-5-oxohexyl phthalate (mEOHP), mono-(7-carboxy-n-heptyl)phthalate (mCHpP), and mono benzyl phthalate (mBzBP) were associated with shorter time to pregnancy, and higher mono-2-ethyl-5-hydroxyhexyl phthalate (mEHHP), mEOHP, and mBzBP with lower odds of subfertility. In men, higher early pregnancy BPS, mCHpP, mono-4-methyl-7-hydroxyoctyl phthalate, mono-4-methyl-7-oxooctyl phthalate, and mono-ethyl phthalate were associated with shorter time to pregnancy or lower odds of subfertility. Higher preconception or early pregnancy BPS, phthalic acid, and mCHpP in women were associated with lower odds of miscarriage, whereas higher mono-carboxy-isoctyl phthalate, mCOCH, and mono-2-(propyl-6-carboxy-hexyl)-phthalate (cxmPHxP) with higher odds of miscarriage (all p-values <0·05).
Preconception and early pregnancy exposure to bisphenols and phthalates may affect couple fertility. Our results should be considered as hypothesis generating and replicated in future studies, possibly including repeated chemical measurements and mixture analysis.
接触双酚和邻苯二甲酸盐等内分泌干扰化学物质可能导致不良的生育能力和早期妊娠结局。
本研究纳入了“R代下一代研究”，这是一项从孕前开始的基于人群的队列研究。在孕前阶段（938名女性）评估尿中邻苯二甲酸盐和双酚的浓度，孕前阶段定义为夫妻积极尝试受孕的时期，以及在妊娠早期（1366名女性和1202名男性，采样时的平均孕周为8.6周）进行评估。通过问卷和超声检查评估受孕时间和流产情况。亚生育能力定义为在12个月内无法受孕或需要辅助生殖技术。
女性孕前尿中双酚S（BPS）和环己烷-1,2-二羧酸单羧基异辛酯（mCOCH）浓度较高与受孕时间延长有关。孕前较高的单-[(2-羧甲基)己基]邻苯二甲酸酯、单-2-乙基-5-氧代己基邻苯二甲酸酯（mEOHP）、单-(7-羧基-n-庚基)邻苯二甲酸酯（mCHpP）和单苄基邻苯二甲酸酯（mBzBP）与较短的受孕时间有关，而较高的单-2-乙基-5-羟基己基邻苯二甲酸酯（mEHHP）、mEOHP和mBzBP与亚生育能力的较低几率有关。在男性中，妊娠早期较高的BPS、mCHpP、单-4-甲基-7-羟基辛基邻苯二甲酸酯、单-4-甲基-7-氧代辛基邻苯二甲酸酯和单乙基邻苯二甲酸酯与较短的受孕时间或较低的亚生育能力几率有关。女性孕前或妊娠早期较高的BPS、邻苯二甲酸和mCHpP与较低的流产几率有关，而较高的单羧基异辛基邻苯二甲酸酯、mCOCH和单-2-(丙基-6-羧基己基)-邻苯二甲酸酯（cxmPHxP）与较高的流产几率有关（所有p值<0.05）。
孕前和妊娠早期接触双酚和邻苯二甲酸盐可能会影响夫妻的生育能力。我们的结果应被视为提出假设，并在未来的研究中进行重复验证，可能包括重复的化学测量和混合物分析。
