Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity.
Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity.
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DOI：
10.1186/1741-7015-11-228
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发表时间：
2013-10-23
期刊：
影响因子：
9.3
通讯作者：
Nilsson EE
中科院分区：
文献类型：
--
作者：
Skinner MK;Manikkam M;Tracey R;Guerrero-Bosagna C;Haque M;Nilsson EE
祖先环境暴露于各种环境因素和有毒物质已被证明可以促进成人发病疾病的表观遗传跨代遗传。目前的工作审查了杀虫剂二氯二苯三氯乙烷（滴滴涕）对肥胖症和相关疾病的潜在跨代作用。将远交妊娠雌性大鼠短暂暴露于溶剂对照或DDT，并将F1代后代繁殖为F2代，将F2代繁殖为F3代。对F1和F3代对照和DDT谱系大鼠进行老化并研究各种病理学。收集F3代雄性精子，以研究对照和DDT谱系雄性精子之间的甲基化。未发现F0代暴露妊娠雌性大鼠的F1代后代（作为胎儿直接暴露）出现肥胖。F1代DDT谱系动物成年后确实发生了肾脏疾病、前列腺疾病、卵巢疾病和肿瘤。有趣的是，F3代（曾孙）有超过50%的男性和女性发展肥胖。在睾丸、卵巢和肾脏中观察到了几种先前显示与代谢综合征和肥胖相关的跨代疾病。疾病的跨代传播是通过女性（卵子）和男性（精子）生殖细胞。F3代精子表型突变，差异DNA甲基化区域（DMR），由DDT诱导的鉴定。许多与DMR相关的基因先前已被证明与肥胖有关。观察结果表明，祖先接触滴滴涕可促进肥胖和相关疾病的遗传。肥胖症等疾病的病因可能部分是由于环境诱导的表观遗传跨代遗传。
Ancestral environmental exposures to a variety of environmental factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The present work examined the potential transgenerational actions of the insecticide dichlorodiphenyltrichloroethane (DDT) on obesity and associated disease. Outbred gestating female rats were transiently exposed to a vehicle control or DDT and the F1 generation offspring bred to generate the F2 generation and F2 generation bred to generate the F3 generation. The F1 and F3 generation control and DDT lineage rats were aged and various pathologies investigated. The F3 generation male sperm were collected to investigate methylation between the control and DDT lineage male sperm. The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats were not found to develop obesity. The F1 generation DDT lineage animals did develop kidney disease, prostate disease, ovary disease and tumor development as adults. Interestingly, the F3 generation (great grand-offspring) had over 50% of males and females develop obesity. Several transgenerational diseases previously shown to be associated with metabolic syndrome and obesity were observed in the testis, ovary and kidney. The transgenerational transmission of disease was through both female (egg) and male (sperm) germlines. F3 generation sperm epimutations, differential DNA methylation regions (DMR), induced by DDT were identified. A number of the genes associated with the DMR have previously been shown to be associated with obesity. Observations indicate ancestral exposure to DDT can promote obesity and associated disease transgenerationally. The etiology of disease such as obesity may be in part due to environmentally induced epigenetic transgenerational inheritance.
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影响因子：
3.6
作者：
Doyle, Timothy J.;Bowman, Jennifer L.;Kim, Kwan Hee
通讯作者：
Kim, Kwan Hee
影响因子：
6.9
作者：
Akahoshi, Toshiki;Uematsu, Akihito;Hashimoto, Shu
通讯作者：
Hashimoto, Shu
影响因子：
3.7
作者：
Guerrero-Bosagna, Carlos;Settles, Matthew;Skinner, Michael K.
通讯作者：
Skinner, Michael K.
DOI：
10.1590/s0102-311x2007001200004
发表时间：
2007-12-01
期刊：
Cadernos de Saúde Pública
影响因子：
--
作者：
Guimarães, Raphael Mendonça;Asmus, Carmen Ildes Rodrigues Fróes;Meyer, Armando
通讯作者：
Meyer, Armando
影响因子：
--
作者：
Billington, CJ;Epstein, LH;Harrison, B
通讯作者：
Harrison, B