Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.
Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.
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DOI：
10.1093/toxsci/kfq179
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Reijo Pera RA
中科院分区：
文献类型：
--
作者：
Kee K;Flores M;Cedars MI;Reijo Pera RA
历史上，由于不可能进行直接的实验分析，环境毒物对人类发育的影响一直是通过流行病学研究推断出来的。然而，近年来，人类多能干细胞的衍生为直接探索人类发育提供了一个潜在的实验系统。在这里，我们使用人类胚胎干细胞（hESCs）来研究环境毒物对人类生殖细胞发育的影响，重点关注原始生殖细胞（PGCs）的分化，这些细胞将继续形成成人的卵母细胞。我们证明，人类PGC数量通过暴露于多环芳烃（PAHs）而减少，多环芳烃是汽油燃烧或烟草烟雾释放的空气污染物中常见的一组有毒物质。此外，我们证明了多环芳烃暴露的不良影响是通过芳烃受体（AHR）和BAX途径介导的。这项研究证明了hESCs作为直接检测环境毒物对人类生殖细胞发育的分子和遗传途径的模型系统的效用。
Historically, effects of environmental toxicants on human development have been deduced via epidemiological studies because direct experimental analysis has not been possible. However, in recent years, the derivation of human pluripotent stem cells has provided a potential experimental system to directly probe human development. Here, we used human embryonic stem cells (hESCs) to study the effect of environmental toxicants on human germ cell development, with a focus on differentiation of the founding population of primordial germ cells (PGCs), which will go on to form the oocytes of the adult. We demonstrate that human PGC numbers are specifically reduced by exposure to polycyclic aromatic hydrocarbons (PAHs), a group of toxicants common in air pollutants released from gasoline combustion or tobacco smoke. Further, we demonstrate that the adverse effects of PAH exposure are mediated through the aromatic hydrocarbon receptor (AHR) and BAX pathway. This study demonstrates the utility of hESCs as a model system for direct examination of the molecular and genetic pathways of environmental toxicants on human germ cell development.
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影响因子：
64.8
作者：
Johnson, J;Canning, J;Tilly, JL
通讯作者：
Tilly, JL
影响因子：
5.3
作者：
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通讯作者：
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影响因子：
5.8
作者：
Fowler, Paul A.;Cassie, Sarah;O'Shaughnessy, Peter J.
通讯作者：
O'Shaughnessy, Peter J.
世界贸易中心队列中多环芳烃，环境烟草烟雾与儿童发育之间的关系。
影响因子：
10.4
作者：
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通讯作者：
Lederman, Sally Ann
DOI：
10.1152/ajpendo.90436.2008
发表时间：
2008-08-01
影响因子：
5.1
作者：
Detmar, Jacqui;Rennie, Monique Y.;Jurisicova, Andrea
通讯作者：
Jurisicova, Andrea