Maternal phthalate and phthalate alternative metabolites and urinary biomarkers of estrogens and testosterones across pregnancy.
Maternal phthalate and phthalate alternative metabolites and urinary biomarkers of estrogens and testosterones across pregnancy.
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DOI：
10.1016/j.envint.2021.106676
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发表时间：
2021-10
影响因子：
11.8
通讯作者：
Strakovsky RS
中科院分区：
文献类型：
--
作者：
Pacyga DC;Gardiner JC;Flaws JA;Li Z;Calafat AM;Korrick SA;Schantz SL;Strakovsky RS
孕妇随处可见来自食品包装材料和个人护理产品的邻苯二甲酸盐。在实验模型中，邻苯二甲酸盐改变了雌激素和睾酮的浓度，但它们在人类怀孕期间影响这些激素的能力尚未得到很好的表征。我们招募了18至40岁的女性参加伊利诺伊州儿童发展研究(I-KILDS)，研究对象为怀孕早期。受试者在怀孕期间(怀孕8-40周)提供了多达5个早晨的尿样，我们将这些样本汇集在一起，用于对19种邻苯二甲酸盐或邻苯二甲酸盐替代代谢物进行定量。个体代谢物(ng/m L)或摩尔总和(nm o l/m L)被用作暴露生物标志物。我们汇总了妊娠13周、28周和34周的尿中八种主要雌激素(SumEstrogen)和两种主要睾酮(SumTestosterone)代谢物的浓度(ng/mL)。我们还估计了雌激素与雄激素的比率。在434名女性中，线性混合效应模型评估了邻苯二甲酸酯/替代品作为连续指标或作为浓度四分位数与总雌激素、总睾酮和雌激素/雄激素比率的关系。在我们的模型中，我们控制了年龄、种族、教育程度、产次、怀孕早期吸烟、孕前体重指数、饮食质量、受孕季节、胎儿性别和激素评估时的孕周。我们还探讨了荷尔蒙评估时的胎龄或胎儿性别是否改变了这些关联。所有的生物标志物和结果都是比重调整的，持续暴露和结果也是自然对数转换的。大多数参与者是非西班牙裔白人(80.9%)，受过大学教育(82.2%)，尿邻苯二甲酸盐/替代代谢物浓度与育龄美国女性相似。总体而言，选定的邻苯二甲酸酯代谢物与雌激素和睾酮呈正相关，但与雌激素/雄激素比率呈负相关。例如，邻苯二甲酸二乙基己酯代谢产物每增加2倍，雌雄激素增加5.1%(95%可信区间：1.8，8.5)，而睾酮增加7.9%(95%可信区间：1.0，15.3)，雌激素/雄激素比值降低−7.7%(95%可信区间：−13.6，−1.4)。然而，邻苯二甲酸酯替代品仅与SumEstroens呈正相关，分别高出2.4%(95%CI：0.4，4.5)和3.2%(95%CI：0.7，5.8)，其代谢物和对苯二甲酸二(2-乙基己基)酯代谢物之和每增加2倍。只有在邻苯二甲酸盐/替代品与SumEstrogen的关联中，才能一致地观察到胎龄和胎儿性别的特定关联，在怀孕中晚期怀孕的女性中，这种关联最强。邻苯二甲酸盐/替代品可能会影响妊娠激素，有可能与胎龄和胎儿性别相关。母体尿雌激素和睾酮是否在邻苯二甲酸盐/替代品与妊娠和胎儿结局的关系中起中介作用，值得进一步研究。
Pregnant women are ubiquitously exposed to phthalates from food packaging materials and personal care products. Phthalates alter estrogen and testosterone concentrations in experimental models, but their ability to impact these hormones in human pregnancy is not well characterized. We recruited women ages 18 to 40 into the Illinois Kids Development Study (I-KIDS) in early pregnancy. Participants provided up to 5 first-morning urine samples across pregnancy (8–40 weeks gestation) that we pooled for quantification of 19 phthalate or phthalate alternative metabolites. Either individual (ng/mL) or molar sums (nmol/mL) of metabolites were used as exposure biomarkers. We summed urinary concentrations (ng/mL) of eight major estrogen (SumEstrogens) and two major testosterone (SumTestosterones) metabolites measured at median 13, 28, and 34 weeks gestation. We also estimated the ratio of estrogens-to-androgens. Linear mixed-effects models assessed relationships of phthalates/alternatives as continuous measures or as concentration quartiles with SumEstrogens, SumTestosterones, and the Estrogen/Androgen ratio in 434 women. In our models we controlled for age, race, education, parity, smoking in first trimester, pre-pregnancy body mass index, diet quality, conception season, fetal sex, and gestational age at hormone assessment. We also explored whether gestational age at hormone assessment or fetal sex modified these associations. All biomarkers and outcomes were specific gravity-adjusted, and continuous exposures and outcomes were also natural log-transformed. Most participants were non-Hispanic white (80.9%), college educated (82.2%), and had urinary phthalate/alternative metabolite concentrations similar to those of reproductive-aged U.S. women. Overall, select phthalate metabolites were positively associated with SumEstrogens and SumTestosterones, but negatively associated with the Estrogen/Androgen ratio. For example, SumEstrogens was 5.1% (95%CI: 1.8, 8.5) higher with every 2-fold increase in sum of di(2-ethylhexyl) phthalate metabolites, while SumTestosterones was 7.9% (95%CI: 1.0, 15.3) higher and Estrogen/Androgen ratio was −7.7% (95%CI: −13.6, −1.4) lower with every 2-fold increase in monoethyl phthalate. However, phthalate alternatives were only positively associated with SumEstrogens, which was 2.4% (95%CI: 0.4, 4.5) and 3.2% (95%CI: 0.7, 5.8) higher with every 2-fold increase in sum of di(isononyl) cyclohexane-1,2-dicarboxylate metabolites and sum of di(2-ethylhexyl) terephthalate metabolites, respectively. Gestational age- and fetal sex-specific associations were only consistently observed for associations of phthalates/alternatives with SumEstrogens, where associations were strongest in mid-to-late pregnancy in women carrying females. Phthalates/alternatives may impact gestational hormones, with potential for gestational age- and fetal sex-specific associations. Whether maternal urinary estrogens and testosterones mediate associations of phthalates/alternatives with pregnancy and fetal outcomes merits further investigation.
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DOI：
10.1186/s12958-015-0100-6
发表时间：
2015-09-04
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Mistry HD;Eisele N;Escher G;Dick B;Surbek D;Delles C;Currie G;Schlembach D;Mohaupt MG;Gennari-Moser C
通讯作者：
Gennari-Moser C
影响因子：
3.5
作者：
Engel, Anika;Buhrke, Thorsten;Lampen, Alfonso
通讯作者：
Lampen, Alfonso
影响因子：
2.3
作者：
Holland, Erica;Simas, Tiffany A. Moore;Waring, Molly E.
通讯作者：
Waring, Molly E.
影响因子：
10.4
作者：
Meeker JD;Hu H;Cantonwine DE;Lamadrid-Figueroa H;Calafat AM;Ettinger AS;Hernandez-Avila M;Loch-Caruso R;Téllez-Rojo MM
通讯作者：
Téllez-Rojo MM
影响因子：
5.8
作者：
Cohn，Barbara A.;Cirillo，Piera M.;Siiteri，Pentti K.
通讯作者：
Siiteri，Pentti K.