Comparison of toxicogenomic responses to phthalate ester exposure in an organotypic testis co-culture model and responses observed in vivo.
Comparison of toxicogenomic responses to phthalate ester exposure in an organotypic testis co-culture model and responses observed in vivo.
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DOI：
10.1016/j.reprotox.2015.10.002
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发表时间：
2015-12
影响因子：
3.3
通讯作者：
Faustman, Elaine M.
中科院分区：
文献类型：
--
作者：
Harris, Sean;Hermsen, Sanne A. B.;Yu, Xiaozhong;Hong, Sung Woo;Faustman, Elaine M.
我们已经开发了一个三维睾丸共培养系统（3D-TCS），模拟在体内睾丸。在本研究中，将3D-TCS中对邻苯二甲酸酯（PE）的转录组学反应与体内大鼠睾丸中的反应进行了比较。来自3D-TCS和体内睾丸的微阵列数据用于比较暴露于发育毒性（DTPE）或发育无毒（DNTPE）邻苯二甲酸酯后基因表达模式的变化。DTPE治疗聚类分别从DNTPE治疗的基础上，在体外和体内的主成分分析。使用GO-Elite软件进行的途径分析表明，DTPE暴露后，与类固醇代谢或生殖发育相关的术语在体外和体内都得到了丰富。DTPE在体外对细胞周期、细胞增殖和细胞凋亡等过程进行了富集，但在体内却没有。基于这些分析，我们得出结论，3D-TCS中的转录组学反应反映了体内邻苯二甲酸酯毒性的关键方面。
We have developed a three-dimensional testicular co-culture system (3D-TCS) which mimics in vivo testes. In this study, transcriptomic responses to phthalate esters (PE’s) were compared in the 3D-TCS with responses in rat testes in vivo. Microarray data from the 3D-TCS and from in vivo testes were used to compare changes in gene expression patterns after exposure to developmentally toxic (DTPE) or developmentally non-toxic (DNTPE) phthalate esters. DTPE treatments clustered separately from DNTPE treatments based on principle components analysis both in vitro and in vivo. Pathway analysis using GO-Elite software showed that terms relating to steroid metabolism or reproductive development were enriched both in vitro and in vivo after DTPE exposure. Processes such as cell cycle, cell proliferation and apoptosis were enriched for DTPE treatments in vitro, but not in vivo. Based on these analyses we concluded that transcriptomic responses in the 3D-TCS reflect key aspects of in vivo phthalate toxicity.
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影响因子：
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