Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures.
Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures.
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DOI：
10.1371/journal.pone.0031901
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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;Guerrero-Bosagna C;Tracey R;Haque MM;Skinner MK
胎儿发育期间的环境因素可诱导生殖系（精子）的永久性表观遗传变化，然后在没有任何后续暴露的情况下将成人发病疾病的表观遗传跨代遗传。使用农药混合物（氯菊酯和驱虫剂避蚊胺），塑料混合物（双酚A和邻苯二甲酸酯），二恶英（TCDD）和碳氢化合物的混合物（喷气燃料，JP 8）的各种环境化合物和相关的混合物的表观遗传跨代行动进行了研究。F0妊娠雌性大鼠在胚胎性腺性别决定期间短暂暴露后，在没有任何环境暴露的情况下获得随后的F1-F3代。研究了对F1、F2和F3代的青春期开始和性腺功能的影响。研究发现，塑料、二恶英和航空燃料可促进女性跨代性早熟（F3代）。生精细胞凋亡受遗传因素影响。卵巢原始卵泡池的大小显着减少与所有治疗transgenetically。检测了F3代精子启动子表观基因组的差异DNA甲基化。在所有暴露谱系雄性的精子中鉴定了差异DNA甲基化区域（DMR），发现在特定暴露谱系内是一致的，但在暴露之间是不同的。鉴定了DMR的几个基因组特征，例如低密度CpG含量。暴露特异性表观遗传生物标志物的确定，可能允许评估与成人发病疾病相关的祖先环境暴露。
Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1–F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.
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影响因子：
5.4
作者：
Corbel V;Stankiewicz M;Pennetier C;Fournier D;Stojan J;Girard E;Dimitrov M;Molgó J;Hougard JM;Lapied B
通讯作者：
Lapied B
DOI：
10.1073/pnas.0610410104
发表时间：
2007-04-03
影响因子：
11.1
作者：
Crews, David;Gore, Andrea C.;Skinner, Michael K.
通讯作者：
Skinner, Michael K.
影响因子：
8
作者：
Biro FM;Galvez MP;Greenspan LC;Succop PA;Vangeepuram N;Pinney SM;Teitelbaum S;Windham GC;Kushi LH;Wolff MS
通讯作者：
Wolff MS
影响因子：
6.7
作者：
Kleiman, Sandra E.;Maymon, Batia Bar-Shira;Yogev, Leah
通讯作者：
Yogev, Leah
影响因子：
3.6
作者：
Baccarelli A;Bollati V
通讯作者：
Bollati V