Study Of Phthalate Exposure During Pregnancy And Impacts On Reproductive Health

Phthalates exert their effects on steroidogenesis through observations of adverse developmental and reproductive effects in laboratory animals and wildlife, which have fueled increasing public concern regarding their potential to impair human fertility. Human data are limited compared with the large amount of experimental evidence in relation to these ubiquitous pollutants. The purposes of our study were to investigate the general exposure of a Chinese pregnant women cohort to phthalates and to assess the association with some reproductive effects.Five phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) were measured in urine samples of pregnant women recruited from China using liquid chromatography-tandem mass spectrometry. The questionnaire and clinical data were evaluated. Associations of phthalate exposure with steroid hormones in the cord blood and steroidogenesis enzyme genes in the placenta were determined by principal component analysis and multiple regression model analysis. The association between urinary concentrations of creatinine-adjusted phthalates metabolites and uterine leiomyoma was assessed by multivariate logistic regression models adjusted by the variables that were significantly associated with uterine leiomyoma.The concentration of observed metabolites in descending order according to the median of the creatinine-adjusetd phthalate monoester is:MMP(67.07μg/g), MEHP(47.76μg/g), MEP(31.97μg/g), MBP(16.86μg/g), MBzP(1.66μg/g). After adjustment for body mass index (BMI), maternal age, menarche age, menstrual cycle, birth weight and neonatal gender, we found significant negative association between MEP and genes expression (p=0.015). For the hormones, there are significant associations between MMP and Testosterone/Estradiol (p=0.028). When urinary phthalate concentrations were grouped into quintiles, the medium level concentration of MEP was inversely associated with the genes, while the lower level of concentration of MEHP had significant association with the genes. The integrated value of testosterone and estradiol was inversely associated significantly with the higher levels of MMP and MEHP, and two quintile groups of MEP.For the model of phthalate metabolite as the continuous variable, after adjustment for age, menstrual cycle and artificial abortion, OR was1.007(CI%1.003-1.012, P=0.001) for the metabolite of MMP. For metabolites of MEP and MBP, the adjusted ORs for UL were1.004(1.000-1.009) and1.007(0.999-1.015), though without statistical significance. We obtained no significant results for MBzP and MEHP, with ORs of0.999(0.988-1.011) and0.997(0.988-1.011) respectively. With the model of phthalates categorized into quartiles and assigned to ordinal categorical variables, the ORs were1.616for MMP (P=0.019),1.512for MEP (P=0.039) and1.515for MBzP (P=0.038). We obtained no significant results for MBP and MEHP, with ORs of1.228(0.840-1.796) and1.078(0.729-1.595) respectively.Although the dose-response relationships for the prenatal exposure induced steroidogenic inhibition is still a puzzle, the data of the present study could explain some of the variation in the observed associations. These preliminary data support the need for prospective studies for a larger population and repeated dynamic monitoring of urinary biomarkers.