■在女性中,暴露于内分泌干扰化学物质可能会加速卵巢储备功能的消耗,并可能与加速生殖衰老和生育能力有关。我们研究了暴露于双酚和邻苯二甲酸酯与抗苗勒管激素浓度的纵向关联。
■2002年至2006年间居住在鹿特丹的18岁或以上的孕妇有资格参加这项纵向前瞻性队列研究。我们测量了1405名妇女在怀孕三个时间点的尿双酚和邻苯二甲酸酯浓度,其中1322名妇女在产后6和/或9年接受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6年和9年后尿双酚和邻苯二甲酸酯代谢物与AMH的关联,和线性混合效应模型来评估与AMH随时间的相关性。根据社会人口统计学和生活方式因素对模型进行了调整。
■在我们的多变量线性回归模型中,我们观察到高尿妊娠平均邻苯二甲酸单异丁酯(mIBP)的关联,单-(2-乙基-5-氧代己基)邻苯二甲酸酯(mEOHP),和邻苯二甲酸单苄基酯(mBzBP)在6年和9年后均具有较低的血清AMH。然而,在对多项测试进行校正后,这些关联并未保留.在我们的研究样本中不存在双酚A与AMH的显著关联。在我们的线性混合效应模型中,更高的mIBP,邻苯二甲酸单(2-乙基-5-羟基己基)酯(mEHHP),mEOHP,mBzBP与较低的总体AMH水平相关(差异-0.07(95%CI-0.13,-0.02),-0.09(-0.15,-0.02),-0.08(95%CI-0.14,-0.02),mIBP每倍增-0.08(-0.13,-0.03)μg/L,mEHHP,mEOHP,和mBzBP分别)(所有错误发现率调整后的p值<0.05)。
■我们发现卵巢储备指数的下降与产前邻苯二甲酸盐暴露的关系。需要研究在大型多种族非怀孕人群中复制我们的结果,并评估暴露对卵巢储备的跨代影响。
■这项研究得到了伊拉斯谟医学中心和鹿特丹伊拉斯谟大学的支持,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,和荷兰皇家艺术与科学学院。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.