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首页> 外文期刊>Reproductive toxicology >In utero exposure to tributyltin chloride differentially alters male and female fetal gonad morphology and gene expression profiles in the Sprague-Dawley rat.
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In utero exposure to tributyltin chloride differentially alters male and female fetal gonad morphology and gene expression profiles in the Sprague-Dawley rat.

机译：在子宫内暴露于三丁基锡氯化物差异地改变了Sprague-Dawley大鼠的男女胎儿性腺形态和基因表达谱。

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摘要

Tributyltin (TBT) is an environmental contaminant commonly used in anti-fouling agents for boats, as well as a by-product from several industrial processes. It has been shown to accumulate in organisms living in areas with heavy maritime traffic thereby entering the food chain. Here, we determined the consequences of in utero exposure to TBT on the developing fetal gonads in the Sprague-Dawley rat. Timed pregnant rats were gavaged either with vehicle or TBT (0.25, 2.5, 10 or 20 mg/kg) from days 0 to 19 or 8 to 19 of gestation. On gestational day 20, dams were sacrificed; fetal testes and ovaries were processed for light (LM) or electron microscopic (EM) evaluation and RNA was prepared for gene expression profiling. At the highest doses of TBT the number of Sertoli cells and gonocytes was reduced, there were large intracellular spaces between Sertoli cells and gonocytes and there was an increased abundance of lipid droplets in the Sertoli cells; EM studies revealed abnormally dilated endoplasmic reticulum in Sertoli cells and gonocytes. In the intertubular region between adjacent interstitial cells, immunostaining for the gap junctional protein connexin 43 was strong in controls, whereas it was reduced or completely absent in treated rats. In the ovaries, TBT (20 mg/kg, days 0-19; 10 mg/kg, days 8-19) reduced the number of germ cells by 44% and 46%, respectively. On examining gene expression profiles in the testis, 40 genes out of 1176 tested were upregulated more than two-fold over control. While no genes were upregulated in the TBT exposed fetal ovary, eight genes were downregulated. In conclusion, in utero exposure to TBT resulted in gender-specific alterations in gonadal development and gene expression profiles suggesting that there may be different adaptive changes to toxicity in developing male and female rats.
机译：三丁基锡（TBT）是一种环境污染物，通常用于船用防污剂以及一些工业过程的副产品。已经表明，它会在海上交通繁忙地区的生物体内积累，从而进入食物链。在这里，我们确定了子宫内TBT暴露对Sprague-Dawley大鼠发育中的性腺的影响。在妊娠的第0至19天或8至19天，给定时怀孕的大鼠灌胃赋形剂或TBT（0.25、2.5、10或20 mg / kg）。在妊娠第20天，将水坝处死。对胎儿的睾丸和卵巢进行光（LM）或电子显微镜（EM）评估，并制备RNA进行基因表达谱分析。在最高剂量的TBT下，Sertoli细胞和生殖细胞的数量减少，Sertoli细胞和生殖细胞之间的细胞内空间很大，Sertoli细胞中的脂滴数量也增加了。 EM研究表明，支持细胞和生殖细胞中的内质网异常扩张。在相邻的间质细胞之间的管间区域，空白连接蛋白连接蛋白43的免疫染色在对照组中很强，而在治疗的大鼠中则减少或完全没有。在卵巢中，TBT（20 mg / kg，第0-19天; 10 mg / kg，第8-19天）分别使生殖细胞数量减少44％和46％。在检查睾丸中的基因表达谱时，测试的1176个基因中有40个基因被上调了两倍以上。虽然在暴露于TBT的胎儿卵巢中没有基因被上调，但是八个基因被下调。总之，在子宫内暴露于TBT会导致性腺发育和基因表达谱的性别特异性改变，这表明发育中的雄性和雌性大鼠对毒性的适应性变化可能不同。

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