Exposure Of Bisphenol-A(BPA) In Relation To ICPP In Girls And The Genetic Mechanism

Background: Bisphenol A(BPA)is one of the highly produced chemicals worldwide,which is mainly used to produce food packaging materials.BPA molecules can leach from those products into foods and drinks,which is the mainly exposre pathway for human beings.The estrogenic effect of BPA has been widely demonstrated.The relationship between BPA exposure and ICPP in girls is still undefined.Polimorphism of genes of hypothalamic-pituitary-gonadal(HPG)axis may be associated with the hereditary susceptibility of BPA exposure induced ICPP in girls.Changing of methylation levels of target genes of DNA methyltransferases(DNMTs)and HPG axis may be epigenetic regulation mechanism of BPA exposure induced ICPP in girlsObjectives: To investigate the relationship between BPA exposure and ICPP in girls,and between dietary habits and BPA exposure.For the genetic susceptibility mechanism,we analyzed the interactive effect of BPA exposure with polymorphism in target genes on the risk of ICPP in girls.Further for the epigenetic regulation mechanism,we analyzed the relationship between BPA exposure and the methylation levels of Cp G islands of target genes.Methods: 157 6-9 years old girls diagnosed as precocious puberty were recruited from the department of endocrinology of Shanghai Children's Medical Center affiliated to Shanghai Jiao Tong University from July 2017 to August 2018.56 girls of them were diagnosed as ICPP after detailed laboratory examinations.At the same time,56 healthy 6-9 years girls were recruited as control group.All of the participants fulfilled the questionnaire survey and their urinary BPA concentrations were detected.Polymophism and methylation levels of Cp G islands of target genes from peripheral blood samples were detected for 56 ICPP girls and 56 healthy girls.Results: Urinary concentrations of BPA before and after adjustment of specific gravity(SG)and creatinine in higher concentration group were all associated with higher risk of ICPP in girls.Decreased serum level of LH and FSH were associated with increased urinary BPA concentrations.Girls who drinked soft drinking contained in cans distributed in higher levels of unrinary BPA.A significant interaction with BPA level adjusted by creatinine and rs5780218 polymorphism of the KISS1 gene in recessive model was observed for ICPP.Girls in the higher concentration group of BPA was associated with higher level of methylation of Cp G islands of DNMT3 B.Conclusions: BPA exposure may increase the risk of ICPP in girls,and interfere the levels of LH and FSH.The habit of drinking soft drinkings in cans may increase the risk of BPA exposure.BPA exposure interacts with rs5780218 polymorphism of the KISS1 gene to incease the risk of ICPP in girls.Higher methylation level of Cp G islands of DNMT3 B may be associated with higer level of BPA expusre.