Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease
Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease
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DOI：
10.1210/en.2006-0640
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发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Skinner, Michael K.
中科院分区：
文献类型：
--
作者：
Anway, Matthew D.;Leathers, Charles;Skinner, Michael K.
成人疾病的胎儿基础在分子水平上知之甚少，不能完全归因于基因突变或单一病因。胚胎暴露于环境化合物已被证明会促进第一代（F1）的各种疾病状态或病变。目前的研究使用内分泌干扰物vinclozolin（抗雄激素化合物）在大鼠性腺性别决定时短暂暴露于胚胎中。来自F1代和检查的所有后续代（F1-F4）的成年动物发展了许多疾病状态或组织异常，包括前列腺疾病、肾脏疾病、免疫系统异常、睾丸异常和肿瘤发展（e. G.乳房）。此外，还出现了许多血液异常，包括高胆固醇血症。这些跨代疾病状态的发生率或患病率很高，并且在所有世代（F1-F4）中保持一致，并且基于先前研究的数据，似乎部分归因于男性生殖系的表观遗传改变。观察结果表明，环境化合物，内分泌干扰物，可以诱导跨代疾病状态或异常，这表明一个潜在的表观遗传病因学和成人发病的疾病的分子基础。
The fetal basis of adult disease is poorly understood on a molecular level and cannot be solely attributed to genetic mutations or a single etiology. Embryonic exposure to environmental compounds has been shown to promote various disease states or lesions in the first generation (F1). The current study used the endocrine disruptor vinclozolin (antiandrogenic compound) in a transient embryonic exposure at the time of gonadal sex determination in rats. Adult animals from the F1 generation and all subsequent generations examined (F1-F4) developed a number of disease states or tissue abnormalities including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development ( e. g. breast). In addition, a number of blood abnormalities developed including hypercholesterolemia. The incidence or prevalence of these transgenerational disease states was high and consistent across all generations (F1-F4) and, based on data from a previous study, appears to be due in part to epigenetic alterations in the male germ line. The observations demonstrate that an environmental compound, endocrine disruptor, can induce transgenerational disease states or abnormalities, and this suggests a potential epigenetic etiology and molecular basis of adult onset disease.