Citation:

Huang, W., D. Bencic, R. Flick, J. Fetke, AND A. Biales. Genome-wide identification of epigenetic changes associated with 17α-ethynylestradiol (EE2) exposure in the fathead minnows. 2019 American Society of Human Genetics (ASHG) Annual Meeting, Houston, TX, October 15 - 19, 2019.

Impact/Purpose:

Presented at the 2019 ASHG meeting

Description:

17α-ethynylestradiol (EE2) is widely used estrogenic chemical present almost ubiquitous in aquatic environments throughout the United States and some other countries. Acting as an endocrine disrupting compound, EE2 can disrupt hormonal homeostasis, leading to developmental disorders, cancer and other diseases. Exposure to EE2 is known to induce expression of vitellogenin, a precursor protein of egg yolk normally only expressed in female fish, in male fish. However, the underlying epigenomic changes associated with vitellogenin induction and phenotypic changes (e.g. feminization), are not well understood. This study was designed to gain insights into such underlying epigenetic regulation mechanisms by evaluating genome-wide DNA methylation changes in CpG sites using the reduced representation bisulfite sequencing (RRBS). Taking advantage of the new and highly contiguous genome reference assembled in house, we used the fathead minnow as the model organism to identify CpG methylation changes before and after exposure to EE2. In our experiment, two groups of male fathead minnow fish, each with 16, were exposed 2.5ng/L and 10ng/L EE2 for 48 hours, respectively. In addition, another two groups not exposed to EE2 were used as control groups: one male group for negative control and the other female group for positive control. We then obtained RRBS data of both liver and brain tissues of all individuals in this experiment. We assessed and compared CpG methylation changes immediately after EE2 exposure in both male liver and brain tissues. We also compared methylation CpG patterns after 7-day and 14-day depuration of EE2 to find if these methylation changes are temporary or potentially long-lasting. This was done separately for liver and brain tissues. Overall, we found that a limited number of CpG regions were subjected to significant methylation changes after 48-hr EE2 exposure in male liver tissue, and the number of affected CpG sites and their methylation level changes were even smaller in male brain tissue. Such epigenetic changes also exhibit dose-dependent effects with larger changes associated with a higher exposure dose. Our initial results show that CpG-sites methylation were changed quickly after EE2 exposure and stayed for a long time after depuration of EE2, indicating EE2 effects could be potentially long lasting. We are working to obtain more detailed results including specific genes/regions and their functions associated with methylation changes, which will also be presented.

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