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

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 （E₁）， 17β -estradiol （E₂）， and estriol （E₃）］ 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 E₁ （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 E₃ in the first trimester （β=0.428， 95%CI： 0.103‒0.752）. MEOHP was positively correlated with E₁ in the second trimester （β=0.734， 95%CI： 0.130‒0.752）， and had a possitive trend with E₁ in the third trimester （β=0.744， 95%CI： -0.140‒1.629）. In addition， MEHP had a negative correlation with E₁ in the second trimester （β=-0.498， 95%CI： -1.063‒0.066）. MEOHP had a positive correlation trend with E₂ （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.