April 28, 2021
Hosted By Dr. Ramji Bhandari
Epigenetics describes the collective mechanisms by which organisms stably adapt to variations in environmental conditions over multiple temporal scales without altering genomic sequence. Aberrant epigenetic modifications, epimutations, are increasingly being recognized as key factors underlying the development of adverse effects. Many pharmaceuticals and other environmental chemicals have been shown to affect the epigenome which may alter response trajectories of exposed organisms to either the initial or subsequent exposures. In many cases, epigenetic alterations can be passed down to subsequent generations, suggesting they have the potential to cause long term effects. Despite the likelihood that epigenetic responses are key determinants in organismal response to chemical exposure, relatively little is known about the impacts of chemical exposure on ecological model species. Here we investigate the effects of the potent xenoestrogen 17a-ethinylestradial on the epigenome of Pimephales promelas (fathead minnow; FHM) at environmentally relevant concentrations. Adult male FHM were exposed for 48h to two concentrations of EE2 or a control and allowed to depurate for 7 or 14 d. Brain and liver were taken at each time point and both genome-wide (reduced representation bisulfite analysis: RRBS) and targeted (esr1) methylation and gene expression analyses were conducted. At 48h, the changes in the pattern of methylation of esr1 were observed in both the liver and brain of exposed males, however the pattern differed among tissues. This was also reflected in the paired RRBS and RNA-seq analysis. Altered methylation patterns persisted, and in some cases changed, over the depuration period. In a second study evaluating the ability of EE2 to alter the expression of small non-coding RNAs (sncRNA) in acute early life stage exposures, both miRNA and piwiRNAs were differentially expressed, as were a number of well-characterized estrogen responsive mRNAs. Though sncRNA responses were found to be variable and were not found to be significant following multiple test corrections, when used as features in classification, they shown to accurately discriminate between exposed and control larvae hold out sets, which we consider a functional test of the biological significance of sncRNA expression. Together, these results suggest that environmentally relevant concentrations of estrogens are able to alter the epigenomes of exposed organisms in both adults and early life stages. Evidence of estrogenic effects remain for up to two weeks following transfer to clean water, suggesting a lasting responses which may have implications on the risk posed by these chemicals.