Effects of exposure to bisphenol A on estrogen homeostasis based on the biomonitoring method in pregnant women
WU Lin-ying and WANG Yi contributed equally to this work
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摘要:
目的 探究孕妇双酚A (bisphenol A, BPA)暴露对孕期雌激素稳态的影响。 方法 选择上海市嘉定区151名孕妇作为研究对象, 进行问卷调查和随机尿液收集。采用超高效液相色谱串联四级杆飞行时间质谱仪测定尿液中BPA和雌酮、17β-雌二醇、雌三醇浓度。在经尿肌酐校正、自然对数转换, 并且去除离群值后, 采用多元线性回归分析尿液中BPA暴露水平与雌激素关系。 结果 孕妇尿样中BPA检出率为99.34%, 尿肌酐校正后浓度中位数为0.65 μg/g。年龄、孕周、家庭年总收入、二手烟接触情况和文化程度与尿液中BPA水平无关联。尿液中雌激素水平随孕期发展呈上升趋势。多元线性回归发现在全部孕妇中, 尿液中BPA水平与雌酮水平(β=0.171, 95%CI: 0.006~0.336)和17β-雌二醇水平(β=0.137, 95%CI: 0.000~0.274)呈正相关。在按孕期分层后, 发现孕晚期尿液中BPA水平与雌酮水平呈正相关(β=0.449, 95%CI: 0.014~0.884)。 结论 上海市孕妇普遍暴露于BPA, 并且孕期BPA暴露水平可能影响雌激素稳态。 Abstract:Objective To investigate the effect of bisphenol A (BPA) on estrogen homeostasis during pregnancy. Methods We selected 151 pregnant women in Jiading District, Shanghai, and a questionnaire survey and collection of urine samples were performed for them.The concentrations of BPA, estrone, 17β-estradiol, and estriol in their urine were determined by ultra-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and corrected by the level of urinary creatinine.The corrected concentrations were transformed by a natural logarithm.After removing outliers, the relationship between urinary BPA and urinary estrogen was analyzed by multiple linear regression analysis. Results The positive rate of urinary BPA in urine samples of pregnant women was 99.34%.After the correction of the urinary creatinine level, the median urinary BPA concentration was 0.65 μg/g.Age, gestational week, total annual household income, second-hand smoke exposure and educational level did not affect urinary BPA level.Urinary estrogen levels were raised with the development of pregnancy.Multiple linear regression analysis showed that urinary BPA level was positively associated with estrone level (β=0.171, 95%CI: 0.006-0.336) and 17β-estradiol level (β=0.137, 95%CI: 0.000-0.274) in all pregnant women.There was a positive correlation between urinary BPA level and urinary estrone level in pregnant women during the third trimester (β=0.449, 95%CI: 0.014-0.884). Conclusions Pregnant women in Shanghai are generally exposed to BPA, and the exposure level of BPA during pregnancy may affect estrogen homeostasis. -
Key words:
- Pregnant women /
- Bisphenol A /
- Estrogen
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表 1 孕妇基本特征与尿液中BPA浓度关系的非参数检验分析
Table 1. Nonparametric test analysis of the relationship between basic characteristics of pregnant women and urinary BPA concentration
基本特征 n(%) BPA H值 P值 基本特征 n(%) BPA H值 P值 年龄(岁) 2.749 0.432 文化程度 0.317 0.712 20~＜25 20(13.24) 1.01(0.50, 1.65)a 本科以下 82(54.30) 0.65(0.42, 1.22) 25~＜30 52(34.44) 0.49(0.32, 1.05) 本科及以上 69(45.70) 0.64(0.35, 1.26) 30~＜35 63(41.72) 0.65(0.46, 1.21) 家庭年总收入(万元) 2.343 0.310 35~44 16(10.60) 0.62(0.31, 1.20) ＜15 39(25.83) 0.85(0.42, 1.49) 孕期(周) 1.597 0.450 15~＜25 71(47.02) 0.57(0.36, 1.03) 孕早期 54(35.76) 0.84(0.40, 1.30) ≥25 41(27.15) 0.61(0.38, 1.20) 孕中期 52(34.44) 0.58(0.36, 1.31) 是否接触二手烟 0.084 0.771 孕晚期 45(29.80) 0.60(0.38, 0.94) 是 63(41.72) 0.58(0.36, 1.21) 否 88(58.28) 0.66(0.40, 1.26) 注: aM(P25，P75)；n(%): 人数(占总人数百分比)。 
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表 2 孕妇尿液中雌激素尿肌酐校正浓度(μg/g)的孕期分布
Table 2. Distribution of urinary creatinine-corrected estrogen concentrations (μg/g) by the trimesters of pregnancy
雌激素 孕早期(n=54) 孕中期(n=52) 孕晚期(n=45) F值b P值b F值c P值c E1 15.98(6.21, 26.82) a 75.64(27.39, 122.72) 93.96(27.68, 148.03) 19.760 < 0.001 36.275 ＜0.001 E2 8.61(5.67, 16.44) 31.28(16.25, 41.84) 36.60(13.55, 59.14) 17.425 < 0.001 30.867 ＜0.001 注: a M(P25, P75)；b组间差异的方差分析；c基于方差分析的组间趋势检验。
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表 3 孕妇尿液中BPA与雌激素水平的多元线性回归
Table 3. Multiple linear regression of association between urinary BPA and estrogen levels in pregnant women
雌激素 模型 总体 孕早期 孕中期 孕晚期 β(95% CI)值 P值 β(95% CI)值 P值 β(95% CI)值 P值 β(95% CI)值 P值 E1 未校正 0.149(-0.057~0.355) 0.155 0.135(-0.111~0.381) 0.277 0.152(-0.131~0.435) 0.285 0.459(0.026~0.892) 0.038 校正 0.171(0.006~0.336) 0.042 0.097(-0.151~0.345) 0.436 0.077(-0.153~0.308) 0.502 0.449(0.014~0.884) 0.044 E2 未校正 0.114(-0.050~0.278) 0.171 0.096(-0.119~0.312) 0.373 0.141(-0.057~0.338) 0.159 0.315(-0.055~0.684) 0.093 校正 0.137(0.000~0.274) 0.049 0.068(-0.142~0.279) 0.516 0.099(-0.064~0.262) 0.228 0.270(-0.129~0.669) 0.179 E3 未校正 -0.072(-0.313~0.168) 0.553 -0.010(-0.231~0.210) 0.925 -0.019(-0.293~0.256) 0.892 0.008(-0.384~0.400) 0.967 校正 -0.023(-0.176~0.129) 0.764 -0.057(-0.259~0.145) 0.574 -0.057(-0.260~0.147) 0.578 -0.050(-0.461~0.361) 0.807 注: 校正年龄(年)、孕周(周)、文化程度、家庭年总收入、二手烟接触情况的回归系数。
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