Laboratory of Evolutionary and Adaptive Physiology, Institute of Life, Earth and Environment, University of Namur, Namur, Belgium.
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Epigenetics. 2022 May;17(5):473-497. doi: 10.1080/15592294.2021.1921337. Epub 2021 May 5.
Organisms exposed to endocrine disruptors in early life can show altered phenotype later in adulthood. Although the mechanisms underlying these long-term effects remain poorly understood, an increasing body of evidence points towards the potential role of epigenetic processes. In the present study, we exposed hatchlings of an isogenic lineage of the self-fertilizing fish mangrove rivulus for 28 days to 4 and 120 ng/L of 17-α-ethinylestradiol. After a recovery period of 140 days, reduced representation bisulphite sequencing (RRBS) was performed on the liver in order to assess the hepatic genome-wide methylation landscape. Across all treatment comparisons, a total of 146 differentially methylated fragments (DMFs) were reported, mostly for the group exposed to 4 ng/L, suggesting a non-monotonic effect of EE2 exposure. Gene ontology analysis revealed networks involved in lipid metabolism, cellular processes, connective tissue function, molecular transport and inflammation. The highest effect was reported for (NIPBL) promoter region after exposure to 4 ng/L EE2 (+ 21.9%), suggesting that NIPBL could be an important regulator for long-term effects of EE2. Our results also suggest a significant role of DNA methylation in intergenic regions and potentially in transposable elements. These results support the ability of early exposure to endocrine disruptors of inducing epigenetic alterations during adulthood, providing plausible mechanistic explanations for long-term phenotypic alteration. Additionally, this work demonstrates the usefulness of isogenic lineages of the self-fertilizing mangrove rivulus to better understand the biological significance of long-term alterations of DNA methylation by diminishing the confounding factor of genetic variability.
生物体在生命早期接触内分泌干扰物，成年后可能会表现出表型改变。尽管这些长期影响的机制仍不清楚，但越来越多的证据表明，表观遗传过程可能发挥了作用。在本研究中，我们将自交的红树林梭鱼的同基因系孵化仔鱼暴露于 17-α-乙炔基雌二醇 4 和 120ng/L 中 28 天。在 140 天的恢复期后，对肝脏进行了简化重亚硫酸盐测序（RRBS），以评估肝脏全基因组的甲基化景观。在所有处理比较中，共报告了 146 个差异甲基化片段（DMFs），主要是暴露于 4ng/L 的组，这表明 EE2 暴露存在非单调效应。基因本体论分析揭示了涉及脂质代谢、细胞过程、结缔组织功能、分子转运和炎症的网络。在暴露于 4ng/L EE2 后，（NIPBL）启动子区域的效应最高（增加 21.9%），这表明 NIPBL 可能是 EE2 长期效应的重要调节剂。我们的结果还表明，DNA 甲基化在基因间区域和潜在的转座元件中具有重要作用。这些结果支持了早期暴露于内分泌干扰物在成年期诱导表观遗传改变的能力，为长期表型改变提供了合理的机制解释。此外，这项工作还证明了自交的红树林梭鱼同基因系在更好地理解 DNA 甲基化长期改变的生物学意义方面的有用性，因为它减少了遗传变异的混杂因素。
