Examining the Impact of Preconception Inorganic Arsenic Exposure on the Mouse Offspring Epigenome

Inorganic Arsenic (iAs) is an environmental toxicant and established carcinogen that is found in drinking water across the globe. Vulnerable populations, namely pregnant women, have been found to be negatively impacted by preconception iAs exposure as indicated by a reduction in length and mean gestational age of their newborns. Since it is unknown as to what occurs at the molecular level to cause these gene expression changes, we analyzed the relationship between preconception exposure to iAs and DNA methylation changes of genes found in liver tissue from the first generation offspring of mice. To determine whether DNA methylation is altered as a result of preconception iAs exposure, selected genes for each sample were bisulfite converted and amplified through PCR. The samples then underwent pyrosequencing to quantify the amount of methylation at each site in the desired sequence. The results revealed that DNA methylation in the selected target genes was not altered by preconception iAs exposure; no statistically significant differences were found between the methylation of mouse liver DNA samples whose parents had been exposed to iAs versus those who had not. Ultimately, this suggests that there could be other epigenetic gene modifiers that are responsible for gene expression changes of these target genes found in newborns. Future studies include analyzing a global methylation array to further investigate the mouse genome, which will provide a concrete conclusion as to whether or not other modifications are the driver of gene expression changes.Bachelor of Scienc