Gene Expression Regulation of Biotransformation Enzymes and Transporters in Placental Barrier

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and toxicology Candidate Mgr. Lucie Stejskalová Supervisor Doc. PharmDr. Petr Pávek, Ph.D. Title of Doctoral Thesis Gene expression regulation of biotransformation enzymes and transporters in placental barrier Placenta is a unique organ facilitating the communication between mother and fetus. It serves as a respiratory, excretory, endocrine and metabolic organ during intrauterine development of the fetus and is necessary for maintenance of pregnancy and for the fetal protection. Syncytiotrophoblast is a single layer that represents the critical morphological and metabolic component of the placental metabolic and exchange barrier. The placental trophoblast contains multiple drug transporters and metabolizing enzymes that form placental metabolic barrier. The levels of the enzymes are not stable and fluctuate throughout pregnancy. Most of the enzymes are expressed at very low mRNA levels, however, in some cases there is absence of any relevant detectable protein or catalytic activity. Cytochrome CYP1A1 is the only placental xenobiotic-metabolizing enzyme of the cytochrome P450 superfamily for which significant expression and catalytic activity have been conclusively demonstrated in placental trophoblasts..