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DNA methylation and expression of estrogen receptor alpha in fathead minnows exposed to 17α-ethynylestradiol
Citation:
Fetke, J., J. Martinson, R. Flick, W. Huang, Mary Jean See, E. Pilgrim, R. DeBry, AND A. Biales. DNA methylation and expression of estrogen receptor alpha in fathead minnows exposed to 17α-ethynylestradiol. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, 233:105788., (2021). https://doi.org/10.1016/j.aquatox.2021.105788
Impact/Purpose:
This work assesses the relationship between DNA methylation and gene expression in response to a known endocrine disrupting compound (EDC). Estrogen receptor alpha has important roles in reproduction, which is negatively affected when fish are exposed to exogenous estrogens such as EE2. This work has implications for susceptibility of organisms exposed to EDCs.
Description:
Estrogens present in the environment interfere with endocrine function and cause decreased fecundity, fitness, and sperm production in fish, as well as feminization of male fish. Physiological effects and alterations of gene expression resulting from estrogen exposure have been thoroughly described in fish. Despite this, little is known about epigenetic alterations, although theses changes are believed to provide the critical linkage of gene expression with the development of adverse effects at higher biological levels. This study investigates alterations of DNA methylation of estrogen receptor alpha (esr1) in brain and liver tissues from male fathead minnows (Pimephales promelas) exposed to either nominal 2.5ng/L or 10ng/L of the synthetic exogenous estrogen, 17α-ethynylestradiol (EE2), in a 48h (2d) exposure. Methylation differences were assessed across all CpG sites in a 2.5kb region of esr1 by targeted deep sequencing of bisulfite treated DNA isolated from liver and brain tissue and esr1 was further analyzed for gene expression changes using RT qPCR. Additionally, methylation and gene expression were assessed from fish depurated for 7 and 14 days to determine the kinetics of methylation. At the end of the 2d EE2 exposure, males exhibited significant differential methylation at several CpG sites in the 5’ upstream region of esr1 in liver tissue, and a moderate inverse relationship was observed between methylation level and expression for specific regions of the gene. We found sex specific methylation differences in liver tissue between untreated female fish and control males. Differential methylation at singular CpG sites in the upstream region of esr1 of both brain and liver tissues indicate potential for epigenetic changes to persist even after gene expression returns to normal levels or is not significantly different. Our results indicate that significant epigenetic changes result when fish are exposed to EE2.
URLs/Downloads:
DOI: DNA methylation and expression of estrogen receptor alpha in fathead minnows exposed to 17α-ethynylestradiol