Myllynen P, Pasanen M, Pelkonen O
Department of Pharmacology and Toxicology, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland.
Placenta. 2005 May;26(5):361-71. doi: 10.1016/j.placenta.2004.09.006.
Pregnant mothers are exposed to a wide variety of foreign chemicals. This exposure is most commonly due to maternal medication, lifestyle factors, such as smoking, drug abuse, and alcohol consumption, or occupational and environmental sources. Foreign compounds may interfere with placental functions at many levels e.g. signaling, production and release of hormones and enzymes, transport of nutrients and waste products, implantation, cellular growth and maturation, and finally, at the terminal phase of placental life, i.e. delivery. Placental responses may also be due to pharmaco-/toxicodynamic responses to foreign chemicals, e.g. hypoxia. On the other hand, placental xenobiotic-metabolizing enzymes can detoxify or activate foreign chemicals, and transporters either enhance or prevent cellular accumulation and transfer across the placenta. The understanding of what xenobiotics do to the placenta and what the placenta does to the xenobiotics should provide the basis for the use of placenta as a tool to investigate and predict some aspects of developmental toxicity. This review aims to give an update of the fate and behavior of xenobiotics in the placenta from the viewpoint of xenobiotic-metabolizing enzymes and transporters. Their response levels will be described according to gestational status and methods used. The effects of foreign chemicals on placental metabolizing enzymes will be discussed. Also, interactions in the transporter protein level will be covered. The role of the placenta in contributing to developmental effects and fetotoxicity will be examined. The toxicological effects of maternal medications, smoking, and environmental exposures (dioxins, pesticides) as well as some possibilities for biomonitoring will be highlighted.
怀孕母亲会接触到各种各样的外来化学物质。这种接触最常见的原因是母亲用药、生活方式因素，如吸烟、药物滥用和饮酒，或职业和环境来源。外来化合物可能在多个层面干扰胎盘功能，例如信号传导、激素和酶的产生与释放、营养物质和代谢废物的运输、着床、细胞生长和成熟，最后，在胎盘生命的末期，即分娩时。胎盘的反应也可能是对外来化学物质的药物/毒理动力学反应，例如缺氧。另一方面，胎盘外源性物质代谢酶可以使外来化学物质解毒或活化，而转运蛋白则可以增强或阻止细胞积累以及跨胎盘转运。了解外源性物质对胎盘的作用以及胎盘对外源性物质的作用，应该为利用胎盘作为工具来研究和预测发育毒性的某些方面提供基础。本综述旨在从外源性物质代谢酶和转运蛋白的角度，更新外源性物质在胎盘中的命运和行为。将根据妊娠状态和使用的方法描述它们的反应水平。将讨论外来化学物质对胎盘代谢酶的影响。此外，还将涵盖转运蛋白水平的相互作用。将研究胎盘在导致发育影响和胎儿毒性方面的作用。将重点介绍母亲用药、吸烟和环境暴露（二噁英、农药）的毒理学影响以及一些生物监测的可能性。
