Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, USA; Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
Toxicol Appl Pharmacol. 2013 Dec 15;273(3):532-41. doi: 10.1016/j.taap.2013.09.024. Epub 2013 Oct 3.
1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p'-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p'-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague-Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p'-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p'-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy.
1,1,1-三氯-2,2-双(2-氯苯基-4-氯苯基)乙烷(o,p'-DDT)是一种有机氯农药和内分泌干扰物，已知能激活雌激素受体。本研究进行了全面的配体和物种比较、剂量和时间依赖性研究，以系统评估 o,p'-DDT 和乙炔雌二醇(EE)在未成熟去卵巢 C57BL/6 小鼠和 Sprague-Dawley 大鼠中引起的子宫生理、形态和基因表达反应。使用定制的 cDNA 微阵列来鉴定保守和不同的差异基因表达反应。两种配体在两种物种中共有 1256 个基因表达差异，其中 559 个基因表现出相似的时间表达谱，表明与 EE 相比，o,p'-DDT 在高剂量时会引起雌激素样作用。然而，51 个基因表现出 o,p'-DDT 引起的物种特异性子宫表达。例如，碳酸酐酶 2 的表达具有物种和配体的差异，这一点通过实时定量 PCR 得到了证实。与基因表达相关的可比时间表型反应的鉴定表明，系统的比较基因表达评估对于阐明啮齿动物子宫肥大中保守和不同的雌激素信号机制是有价值的。
