典型邻苯二甲酸酯类物质暴露与孕期雌激素稳态的联系

Effect of exposure to typical phthalate esters on estrogen homeostasis during pregnancy

【目的】研究孕妇2种典型邻苯二甲酸酯类化合物(PAEs)[邻苯二甲酸二正丁基酯(DBP)和邻苯二甲酸二(2-乙基己基)酯(DEHP)]暴露与雌激素稳态之间的关系。【方法】2021年,在将上海市嘉定区分为东、西、南、北、中5个地理区域后,从每个区域随机选取全孕期孕妇,共抽取151名孕妇,进行问卷调查,采集孕妇孕早、中和晚期随机尿样。采用超高效液相色谱串联四级杆飞行时间质谱法分析尿液中1种DBP代谢产物[邻苯二甲酸单丁基酯(MBP)]、2种DEHP代谢产物[邻苯二甲酸单乙基己基酯(MEHP)和邻苯二甲酸单(2-乙基-5-氧己基)酯(MEOHP)]和3种雌激素[雌酮(E_(1))、17β-雌二醇(E_(2))、雌三醇(E_(3))]。在PAEs代谢产物水平和雌激素浓度经自然对数转换后,应用多元线性回归校正潜在混杂因素,分析PAEs代谢产物水平与雌激素浓度的关系。【结果】孕妇尿液中3种PAEs代谢产物检出率超过98%。MBP、MEHP、MEOHP肌酐校正浓度中位数分别为5.18、0.59、4.23 mg·kg^(−1)。在全孕期孕妇中,MEOHP与E_(1)呈正相关(β=0.450,95%CI:0.057~0.844);MBP与E_(3)呈正相关(β=0.250,95%CI:0.034~0.465)。按孕期分层后,孕早期时,MBP与E_(3)呈正相关(β=0.428,95%CI:0.103~0.752);孕中期时,MEOHP与E_(1)呈正相关(β=0.734,95%CI:0.130~0.752),并在孕晚期时与E1呈正相关趋势(β=0.744,95%CI:−0.140~1.629)。此外,MEHP在孕中期与E_(1)呈负相关趋势(β=−0.498,95%CI:−1.063~0.066);MEOHP在孕晚期与E_(2)(β=0.628,95%CI:−0.101~1.356)呈正相关趋势。【结论】PAEs暴露可能干扰孕期雌激素稳态,而且在不同孕期存在差异。鉴于本研究为横断面研究,需要更多研究验证该发现。

[Objective]To study the relationship between the exposure to two kinds of phthalate esters(PAEs)[Di-N-butyl phthalate,(DBP)and Di-(2-ethylhexyl)phthalate(DEHP)]and estrogen homeostasis in pregnant women.[Methods]In 2021,we classified the Jiading District of Shanghai into five geographical areas,east,west,south,north and central.A total of 151 pregnant women from each area were selected for questionnaire survey,with random urine samples during first,second,and third trimesters collected.A DBP metabolite[Mono-N-butyl phthalate(MBP)]and two DEHP metabolites[Mono(2-ethylhexyl)phthalate(MEHP),Mono(2-ethyl5-oxohexyl)phthalate,(MEOHP)]and three estrogens[estrone(E_(1)),17β-estradiol(E_(2)),and estriol(E_(3))]in urine were determined by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry.After a natural logarithmic transformation of PAEs metabolite levels and estrogen concentration,multivariable linear regression was used to control potential confounders and determine the relationship between PAEs metabolite levels and estrogen concentration.[Results]The detection rates of three PAEs metabolites in urine of pregnant women were more than 98%.The median corrected concentrations of MBP,MEHP and MEOHP were 5.18,0.59 and 4.23 mg·kg^(−1),respectively.During the whole pregnancy,MEOHP was positively correlated with E_(1)(β=0.450,95%CI:0.057‒0.844),and MBP was positively correlated with E3(β=0.250,95%CI:0.034‒0.465).Stratified by trimesters,MBP was positively correlated with E_(3) in the first trimester(β=0.428,95%CI:0.103‒0.752).MEOHP was positively correlated with E_(1) in the second trimester(β=0.734,95%CI:0.130‒0.752),and had a possitive trend with E_(1) in the third trimester(β=0.744,95%CI:−0.140‒1.629).In addition,MEHP had a negative correlation with E_(1) in the second trimester(β=−0.498,95%CI:−1.063‒0.066).MEOHP had a positive correlation trend with E_(2)(β=0.628,95%CI:−0.101‒1.356)in the third trimester.[Conclusion]PAEs exposure may interfere with estrogen homeostasis during pregnancy and differs by trimesters.Given the cross-sectional nature of this study,it warrants further study to validate the findings.