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首页> 外文期刊>PLoS Genetics >Germline and reproductive tract effects intensify in male mice with successive generations of estrogenic exposure
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Germline and reproductive tract effects intensify in male mice with successive generations of estrogenic exposure

机译：连续几代雌激素暴露的雄性小鼠中生殖细胞和生殖道的作用增强

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The hypothesis that developmental estrogenic exposure induces a constellation of male reproductive tract abnormalities is supported by experimental and human evidence. Experimental data also suggest that some induced effects persist in descendants of exposed males. These multi- and transgenerational effects are assumed to result from epigenetic changes to the germline, but few studies have directly analyzed germ cells. Typically, studies of transgenerational effects have involved exposing one generation and monitoring effects in subsequent unexposed generations. This approach, however, has limited human relevance, since both the number and volume of estrogenic contaminants has increased steadily over time, intensifying rather than reducing or eliminating exposure. Using an outbred CD-1 mouse model, and a sensitive and quantitative marker of germline development, meiotic recombination, we tested the effect of successive generations of exposure on the testis. We targeted the germline during a narrow, perinatal window using oral exposure to the synthetic estrogen, ethinyl estradiol. A complex three generation exposure protocol allowed us to compare the effects of individual, paternal, and grandpaternal (ancestral) exposure. Our data indicate that multiple generations of exposure not only exacerbate germ cell exposure effects, but also increase the incidence and severity of reproductive tract abnormalities. Taken together, our data suggest that male sensitivity to environmental estrogens is increased by successive generations of exposure.
机译：实验和人类证据支持了发育雌激素暴露引起男性生殖道异常星座的假说。实验数据还表明，某些诱发效应在裸露的男性后代中仍然​​存在。这些多代和跨代效应被认为是种系表观遗传的变化所致，但是很少有研究直接分析生殖细胞。通常，跨代效应的研究涉及暴露一个世代，并监测随后未暴露的世代的效应。但是，由于雌激素污染物的数量和体积都随着时间的推移而稳定增加，而不是减少或消除暴露，因此这种方法在人类中的应用受到了限制。我们使用远交CD-1小鼠模型以及种系发育，减数分裂重组的敏感和定量标记，我们测试了连续几代暴露对睾丸的影响。我们通过接触合成雌激素，炔雌醇，在狭窄的围生期窗口内将种系作为目标。复杂的三代暴露协议使我们能够比较个体，父代和祖父母（祖传）暴露的影响。我们的数据表明，多代接触不仅加剧了生殖细胞接触的影响，而且还增加了生殖道异常的发生率和严重性。两者合计，我们的数据表明，男性对环境雌激素的敏感性通过连续几代暴露而增加。

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