The Aryl Hydrocarbon Receptor in the Human Placental Trophoblast: The Impact of Nutraceuticals and Natural Products
Abstrakt
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 significantly inducible in the human placental trophoblast, with significant enzymatic activities having been described. Herein, we summarize recent findings related 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.