Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.
Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.
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DOI：
10.1371/journal.pone.0046249
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Skinner MK
中科院分区：
文献类型：
--
作者：
Manikkam M;Tracey R;Guerrero-Bosagna C;Skinner MK
环境化合物可以促进胚胎性腺性别决定过程中祖先暴露后后代中成人发病疾病的表观遗传跨代遗传。本研究检测了二恶英（2，3，7，8-四氯二苯并[p]二恶英，TCDD）促进疾病表观遗传跨代遗传和精子DNA甲基化表位突变的能力。妊娠F0代雌性大鼠在胎儿第8至14天暴露于二恶英，并在F1和F3代大鼠中评价成年发病。F1和F3代总发病率和多发病率增加。F1代二恶英家系中前列腺疾病、卵巢原始卵泡丢失和多囊卵巢疾病的患病率增加。在F3代二恶英谱系动物中，雄性肾脏疾病、雌性青春期异常、卵巢原始卵泡丢失和多囊卵巢疾病增加。对F3代精子表观基因组的分析在基因启动子中鉴定出50个差异DNA甲基化区域（DMR）。这些DMR为跨代疾病和祖先环境暴露提供了潜在的表观遗传生物标志物。观察表明，二恶英暴露的怀孕女性促进表观遗传跨代遗传成人发病的疾病和精子表观突变。
Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.
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影响因子：
15.8
作者：
Baccarelli A;Giacomini SM;Corbetta C;Landi MT;Bonzini M;Consonni D;Grillo P;Patterson DG;Pesatori AC;Bertazzi PA
通讯作者：
Bertazzi PA
DOI：
10.1016/j.bbagrm.2011.03.007
发表时间：
2011-08
影响因子：
4.7
作者：
Hauser, Marie-Theres;Aufsatz, Werner;Jonak, Claudia;Luschnig, Christian
通讯作者：
Luschnig, Christian
影响因子：
3.8
作者：
Flaws, JA;Sommer, RJ;Hirshfield, AN
通讯作者：
Hirshfield, AN
影响因子：
4
作者：
Kakeyama, Masaki;Sone, Hideko;Tohyama, Chiharu
通讯作者：
Tohyama, Chiharu
影响因子：
3.7
作者：
Guerrero-Bosagna, Carlos;Settles, Matthew;Skinner, Michael K.
通讯作者：
Skinner, Michael K.