Association Of Bisphenol A Exposure During Pregnancy With Endocrine Diseases And Birth Outcomes During Pregnancy

Pregnancy endocrine disease played important effect on maternal and fetal health.Emerging environmental endocrine disruptor,bisphenol A(Bispheol A,BPA)owning to its chemical structure similar to estrogen,thyroid hormone,etc,exhibited estrogen,thyroid hormone resistance,resistance to androgen,and many other disrupting effects.Because of pregnant women are particularly sensitive to the environment endocrine disruptors,our study was aim to explore the relationship between prenatal BPA exposure and GDM,maternal-infant thyroid hormone levels,and hormones related to metabolism in cord blood.Part 1.We aimed to investigate whether maternal urinary BPA concentration is associated with gestational diabetes mellitus(GDM).This study included 620 pregnant women from Shanghai,China 2012-2013.Maternal urinary BPA concentration was measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).GDM(n=79)was diagnosed according to the criteria of the International Association of Diabetes and Pregnancy Study Groups(IADPSG).Multivariate regressions were used to explore the relationships of urinary BPA with GDM,plasma glucose levels in the 75 g 2-h oral glucose tolerance test(OGTT).As a results,the geometric mean of BPA was 1.32 μg/L.After adjustment for maternal age,education,husband smoking,pre-pregnacy BMI and urinary creatinine concentration,plasma glucose at 2 hour in the 75 g OGTT was 0.36mmol/L lower(95% CI:-0.73,0.01)for women with urine BPA in the high vs.the low tertile.For each unit increase in natural log-transformed BPA,the odds of GDM was reduced by 27%(OR=0.73,95% CI: 0.56,0.97).Part 2.We aimed to evaluate the association of maternal urinary BPA concentration with thyroid hormone levels in mothers and newborns in a prospective birth cohort by enrolling 398 pregnant women.We measured BPA concentration in maternal urine samples and the concentration of free triiodothyronine(FT3),free thyroxin(FT4),thyroid stimulating hormone(TSH),and thyroid peroxidase antibody(TPO-Ab)in cord blood.Maternal FT4,TSH and TPO-Ab concentration were obtained from medical records.With each unit of increase in natural log-transformed BPA,no changes were found for maternal natural-log transformed FT4(β=0.0004pmol/l,95% CI:-0.01,0.01)or TSH level(β=-0.01 m IU/ml,95% CI:-0.05,0.04).Of398 newborns,no associations were found between urinary BPA concentration and FT3,FT4,TSH or TPO-Ab level in either male or female newborns.Part 3.We explored the relationship between prenatal urinary bisphenol A(BPA)concentrations and infants’ birth weight,and biomarkers in cord blood by enrolling430 mother-infant paries.We measured markers of glucose-lipid metabolic(insulin,c-peptide,total cholesterol,triglyceride,high density lipoprotein,low density lipoprotein,non-esterified fatty acid),markers of oxidative stress(superoxide dismutase)and markers of inflammation(hypersensitivity-c-reactive protein,hs-CRP)(n = 430 subjects).We used linear liner models to assess relationships between BPA concentration and birth outcome.After adjustment for urinary creatinine,gestional age,maternal pre-pregnancy BMI,maternal age,education,passive smoking,prenatal BPA concentration was negatively associated insulin and C-pepite levels in cord serum in female subjects.A unit increase in ln BPA concentration was associated with lower serum concentrations of insulin(-0.09 u IU/ml,95% CI:-0.17,-0.01)and lower C-pepite level(-0.09 ng/ml,95% CI:-0.17,-0.01)was also seen in female subjects.Also,a unit increase in ln BPA concentration was associated with higher serum concentrations of triglyceride(0.11 mg/dl 95% CI:0.02,0.19),and higher risk for hs CRP positive rate(OR=1.5,95% CI: 1.02,2.22)Part 4.BPA exposure had toxicity effect on placental function and fetal growth development.However,the mechanism of the disrupted effect is not yet clear.This study was to explore the effect of BPA on expression of insulin-like growth factor 2(IGF2)in HTR8/SVneo cells.As a result,we found that IGF-2 gene express was significantly decreased by BPA exposure(0.001 u M,0.01 u M,0.1 u M,1.0 u M,10 u M).The result showed that the down-regulated IGF2 gene expression by the low concentrations of BPA maybe conttributed for restriction of placent and fetus growth development.Conclusion:Our findings suggest that exposure to BPA during pregnancy may be related to lower glucose value in OGTT and lower risk of GDM.In infants,we found prenatal BPA exposure was associatd with reduced c-peptide and insulin concentration.Additionally,we did not found the disrupt effect between BPA exposure and thyroid hormers in both maternal and infants.Furthermore,our study needed additional research to confirm.