ABSTRACT
The aryl hydrocarbon receptor (AHR) and its heterodimer AHR nuclear translocator (ARNT) form a ligand-activated transcription complex that regulates the expression of numerous target genes involved in the biotransformation of both xenobiotic and endogenous compounds, including cytochrome P450 enzymes CYP1A1, CYP1A2, and CYP1B1; glutathione S-transferase GST1; UDP-glucuronosyltransferases UGT1A1 and UGT1A6; NAD(P)H-dependent quinone dehydrogenase NQO1; aldehyde dehydrogenase ALDH3A1; and breast cancer resistance protein. Placental expression, as well as the ontogeny of AHR, has been recently described both in human or rat placenta, and the regulation of its target genes has been studied in the placental trophoblast. Interestingly, of the AHR target genes, only cytochrome P450 CYP1A1 has been found to be signicantly inducible in the human placental trophoblast, with signicant enzymatic activities having been described. Herein, we summarize recent ndings related
22.1 Introduction .......................................................................................................................... 330 22.1.1 Placenta ..................................................................................................................... 330
22.1.1.1 Metabolic Function of the Placenta ........................................................... 330 22.2 The AHR .............................................................................................................................. 330
22.2.1 Placental Localization of AHR ................................................................................ 332 22.3 Cytochrome CYP1A1 ........................................................................................................... 333
22.3.1 Expression CYP1A1 in Placental Tissue .................................................................. 333 22.3.2 Biotransformation of Exogenous Compounds by CYP1A1 ..................................... 334 22.3.3 Biotransformation of Endogenous Compound by CYP1A1 ..................................... 334 22.3.4 Inhibition of CYP1A1 ............................................................................................... 335 22.3.5 Smoking and Placental CYP1A1 .............................................................................. 335 22.3.6 Environmental Contaminants ................................................................................... 336
22.4 Natural or Dietary Ligands of AHR ..................................................................................... 336 22.5 Cross-Talk from AHR to Other Signaling Pathways in the Fetoplacental Unit ................... 336 22.6 Conclusion ............................................................................................................................ 338 Acknowledgment ........................................................................................................................... 338 References ...................................................................................................................................... 338
to the toxicological consequences of AHR activation and CYP1A1 induction during human gestation via natural compounds, as well as the consequences of this induction for prenatal toxicology.
