Blaauwendraad Sophia M, Dykgraaf Ramon H M, Gaillard Romy, Liu Mengling, Laven Joop S, Jaddoe Vincent W V, Trasande Leonardo
The Generation R Study Group, Erasmus Medical Center (MC), University Medical Center, Rotterdam, the Netherlands.
Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
EClinicalMedicine. 2024 Jul 17;74:102734. doi: 10.1016/j.eclinm.2024.102734. eCollection 2024 Aug.
In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations.
Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors.
In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) μg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05).
We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve.
This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.
在女性中，接触内分泌干扰化学物质可能会加速卵巢储备的消耗，并可能与生殖衰老加速和生育能力下降有关。我们研究了双酚和邻苯二甲酸盐暴露与抗苗勒管激素浓度之间的纵向关联。
2002年至2006年居住在鹿特丹的18岁及以上孕妇有资格参与这项纵向前瞻性队列研究。我们在1405名孕妇的孕期三个时间点测量了尿液中双酚和邻苯二甲酸盐的浓度，其中1322名女性在产后6年和/或9年进行了血清抗苗勒管激素（AMH）测量。我们进行了线性回归模型，以评估产后6年和9年尿液中双酚和邻苯二甲酸盐代谢物与AMH的关联，并进行线性混合效应模型以评估随时间与AMH的关联。模型对社会人口统计学和生活方式因素进行了调整。
在我们的多变量线性回归模型中，我们观察到较高的尿妊娠平均单异丁基邻苯二甲酸盐（mIBP）、单（2-乙基-5-氧代己基）邻苯二甲酸盐（mEOHP）和单苄基邻苯二甲酸盐（mBzBP）与产后6年和9年较低的血清AMH相关。然而，在多重检验调整后，这些关联不再存在。在我们的研究样本中，双酚A与AMH没有显著关联。在我们的线性混合效应模型中，较高的mIBP、单（2-乙基-5-羟基己基）邻苯二甲酸盐（mEHHP）、mEOHP和mBzBP与较低的总体AMH水平相关（mIBP、mEHHP、mEOHP和mBzBP每增加一倍，差异分别为-0.07（95%CI -0.13，-0.02）、-0.09（-0.15，-0.02）、-0.08（95%CI -0.14，-0.02）和-0.08（-0.13，-0.03）μg/L）（所有错误发现率调整后的p值<0.05）。
我们发现产前邻苯二甲酸盐暴露与卵巢储备指标下降有关。需要在大型多民族非孕妇群体中重复我们的结果，并评估暴露对卵巢储备的跨代影响。
本研究得到了伊拉斯姆斯医学中心和鹿特丹伊拉斯姆斯大学、荷兰卫生研究与发展组织、欧洲研究理事会、荷兰心脏基金会、荷兰糖尿病基金会、欧盟地平线2020研究与创新计划、美国国立卫生研究院、安什实验室韦伯斯特公司以及荷兰皇家艺术与科学院的支持。
