父代双酚 A 暴露导致的心脏疾病的跨代遗传。
Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure.
机构信息
Department of Molecular Biology, Faculty of Biology, University of León, Campus Vegazana s/n, León, 24071, Spain.
Spanish Institute of Oceanography (IEO), Promontorio de San Martín s/n, 39004, Santander, Spain.
出版信息
Environ Pollut. 2015 Nov;206:667-78. doi: 10.1016/j.envpol.2015.08.016. Epub 2015 Aug 31.
Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor β mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations.
双酚 A（BPA）是一种用于制造塑料设备的内分泌干扰物，在环境中普遍存在，与人类不孕、肥胖或心血管疾病有关。转录组和表观基因组的改变是这些疾病的背后原因，当生殖细胞受到影响时，这些疾病可能会在代际间遗传。为了评估父本暴露对后代发育的潜在影响，成年斑马鱼雄性在精子发生期间暴露于 BPA 中，并与未经处理的雌性交配。结果表明，后代的心力衰竭率在 F2 时增加，同时在 F1 胚胎中涉及心脏发育的 5 个基因下调。此外，BPA 导致 F0 和 F1 精子残留 mRNA 减少，这些 mRNA 与早期发育有关。结果显示，由于胰岛素受体 β mRNA 的下调，胰岛素信号通路的变化具有父系遗传，这表明 BPA 雄性暴露与后代的心脏发生障碍之间存在联系。
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