Human placenta: a human organ for developmental toxicology research and biomonitoring.
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.
Myllynen
P
P
Department of Pharmacology and Toxicology, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland. paivi.k.myllynen@oulu.fi
Pasanen
M
M
Pelkonen
O
O
D000818:Animals; D001693:Biological Transport, Active; D004784:Environmental Monitoring; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism; D008658:Inactivation, Metabolic; D008954:Models, Biological; D018384:Oxidative Stress; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D015262:Xenobiotics / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*
D015262:Xenobiotics