The Effects Of Prenatal Bisphenol A Exposure On Offspring's Neurodevelopment And Related Mechanism

Section one.The effects of prenatal bisphenol A exposure on children neurodevelopment Background: Several epidemiological studies suggest that prenatal exposure to BPA may interfere with thyroid hormones in cord blood and the neurodevelopment of pre-school and school-age children.However,a limited number of studies are available for effects during children at a younger age,especially in China.Methods: Based on Laizhou Wan Birth Cohort(LWBC),we measured BPA concentrations in maternal urine among 506 pregnant women and thyroid hormones in cord blood(n=250).Neurodevelopment of their children was assessed using the Gesell Development Schedules at 12 months(n=368)and 24 months(n=296).Linear regression and generalized linear models were used to analyze the association between prenatal BPA exposure and the children's developmental quotient scores(DQs),and thyroid hormones.Results: The median of maternal BPA concentration was 0.48 ?g/L or 1.05 ?g/g creatinine.Maternal BPA concentrations were adversely associated with children DQs at 12 months of age,with a 10-fold increase in prenatal BPA concentrations correlated to 1.43-point decrease in DQs in the adaptive domain(?=-1.43;95% CI:-2.30 to-0.56,p=0.001).When stratified by gender,prenatal BPA concentrations were adversely associated with the adaptive domain DQs among boys(p-trend=0.012)and girls(p-trend=0.028)and the social domain DQs(p-trend=0.019)only among girls.At 24 months of age,the significant adverse association was only found in the language domain among girls(?=-1.69;95% CI:-3.23 to-0.15,p=0.032).We also found that the prenatal BPA concentrations were adversely correlated with TT4 in cord blood(?=-0.04;95% CI:-0.06 to-0.01,p=0.002)and girls may be more vulnerable(?=-0.06;95% CI:-0.09 to-0.03,p=0.000).Conclusion: Based on a Chinese population,we found potential impacts of prenatal BPA exposure on childhood neurodevelopment at 12 and 24 months of age and thyroid hormones in cord blood,especially among girls.Section two.The effects of prenatal bisphenol A exposure on zebrafish neurobehavioral and related mechanismObjective: BPA is a kind of EDCs(Endocrine Disrupting Chemicals),this study used the zebrafish animal model to investigate the effects of BPA on the development and neurobehavioral of zebrafish,and explores the underlying mechanisms.Methods: The zebrafish fertilized eggs that developed to 4 hpf(hourpost fenilized,hpf)were treated with different concentrations of BPA(0?2.5?25?250?2500 ?g/L).And we observed and recorded survival rate,malformation rate and hatching rate,24 hpf autonomic movement,48 hpf heart rate in zebrafish.And the neurobehavioral test of larval zebrafish that developed to 144 hpf was performed.Then we collected larval fish and tested the changes of thyroid hormone levels and related gene expression levels.Results: The BPA exposure did not affect the survival rate,malformation rate and hatching rate of 144 hpf zebrafish.Compared with the control group,the autonomic movement in 24 hpf and heart rate in 48 hpf of zebrafish embryos that exposed to 2500 ?g/L BPA decreased(P<0.05),and the total distance and average speed of larval zebrafish that developed to 144 hpf also decreased(P<0.05).The behavior of larval zebrafish exposed to 250 ?g/L and 2500 ?g/L BPA changed on locomotor activity,mainly including the decrease of total exercise distance(P<0.05).We also found that the thyroid hormone levels(TT4,FT3,FT4)of larval zebrafish that exposed to high concentrations of BPA were significantly reduced(P<0.05),and the expression of thyroid hormone-related synthetic and regulatory genes(Tg,NKX 2.1)increased(P<0.05).Conclusion: This study suggests that BPA has developmental toxicity and neurotoxicity to zebrafish,the effects may be mediated through thyroid hormone pathways.