Influence of Prenatal Exposure to Phthalates and Phenols on DNA Methylation in Inflammatory Genes

• Main Authors: Yi-Hua Lin, 林依樺
• Other Authors: Chen-Yu Liu
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/85582110887103449917

碩士 === 國立臺灣大學 === 環境衛生研究所 === 103 === Background: Children’s health has been a great concern, and this study investigate epigenetic modifications changes and these impact on specific gene expression in children health outcome through maternal exposures of phthalates (i.e. di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), diethyl phthalate (DEP) ) and phenols (i.e. bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) ). Evidence for the animal experiences showed that in utero and early postnatal expose these compounds may lead to a comprehensive child health defects. It was that the possible problem through the low level and unknown mechanism have regulated the epigenetic molecular pathways to change gene expressions. Therefore, we try to evaluate the association between different phthalates metabolites, as well as prenatal phenols exposures, and the epigenetic alteration in Inflammatory Genes. Methods: This study was based on the Taiwan Birth Panel Study (TBPS), which was enrolled from April 2004 to January 2005. A total of 486 mother-infant paired in this study (the Taiwan Birth Panel Study). Three phenols in cord blood, and four phthalates metabolites in urine. In recently experiments, we found the best PCR condition of the selected genes, including IFN-r, and iNOS, so we used PyroMark Q96 ID to analyze two genes’ epigenetic DNA methylation in subjects’ cord blood samples.The gene-specific DNA methylation patterns were quantified in umbilical cord blood using IFN-r and iNOS by pyrosequencing. IFN-r has been identified as a prerequisite in several models of inflammatory and autoimmune diseases. iNOS expression has been found to respond rapidly to different stimuli, including immunostimulatory cytokines, bacterial products, or infection (Alderton et al. 2001). Results: Mean (SD) methylation levels of iNOS and IFN-r were 67.96 (5.33)% and 89.06 (4.29) % (range: 51.84-91.65% and 64.57-96.26%), respectively. Simple and multiple linear regression models shown a negative association between IFN-r methylation level and 3rd urine MEP concentration (crude model: β= -0.023, p<0.01 ; adjusted model: β= -0.029, p<0.01). iNOS methylation level and maternal blood IgE concentration had a negative association (adjusted model: β= -412.584, p<0.05). IFN-r methylation level and cord blood IgE concentration had a negative association (adjusted model: β= -6.416, p<0.05). 2 years old blood IgE concentration and 3rd urine MEHP concentration had a negative association (adjusted model: β= -8.015, p<0.05). Cord blood IgE concentration and cord blood OP concentration had a negative association (adjusted model: β= -1.062, p<0.01). Conclusion: Our result suggest that prenatal exposure to phthalates compounds like MEP, MEHP and OP may adverse effect on inflammatory gene methylation patterns and fetal’s developmental immune system. Otherwise, our study find out different iNOS postion 1 methylation level between male and female babies.