TY - JOUR
T1 - Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption
AU - Collier, AC
AU - Tingle, MD
AU - Paxton, JW
AU - Mitchell, MD
AU - Keelan, Jeffrey
PY - 2002
Y1 - 2002
N2 - BACKGROUND: The rationale for this study was to assess the expression, activity and localization of the enzymes uridine diphosphate glucuronosyltransferase (UGT), beta-glucuronidase, cytochrome P450 1A (CYP1A) and cytochrome P4590 2E1 (CYP2E1) in first trimester human placenta and to gauge the effects of maternal variables on placental metabolism METHODS: CYP1A, CYP2E1, UGT and beta-glucuronidase activities were assessed in 25 placentas using ethoxyresorufin, chlorzoxazone, 4-methylumbelliferone and 4-methylumbelliferone glucuronide respectively. Protein expression and localization were detected by immunoblot and immunohistochemistry. All statistics were non-parametric. RESULTS: UGT, beta-glucuronidase and CYP1A activities were detected in all placentas sampled; CYP2E1 was undetectable. CYP1A, UGT1A UGT2B, proteins were detected in all placentas (n = 6) tested and CYP2E1 in 4/6 placentas sampled and were localized to the syncytium. UGT and CYP1A activities were significantly elevated in the placentas of mothers who smoked (P <0.05 and P <0.001 respectively) and were greatest in women who both smoked and drank-alcohol (P <0.05 and P <0.01 respectively). Enzyme activities were significantly negatively correlated with gestational age (P <0.05, r = 0.54, UGT) and maternal age respectively (P <0.001, r = 0.63, CYP1A). beta-Glucuronidase activity did not differ with patient variables. CONCLUSIONS: Metabolism of compounds by the human placenta in the first trimester may be affected by maternal and environmental factors altering the activity of constitutive metabolizing enzymes.
AB - BACKGROUND: The rationale for this study was to assess the expression, activity and localization of the enzymes uridine diphosphate glucuronosyltransferase (UGT), beta-glucuronidase, cytochrome P450 1A (CYP1A) and cytochrome P4590 2E1 (CYP2E1) in first trimester human placenta and to gauge the effects of maternal variables on placental metabolism METHODS: CYP1A, CYP2E1, UGT and beta-glucuronidase activities were assessed in 25 placentas using ethoxyresorufin, chlorzoxazone, 4-methylumbelliferone and 4-methylumbelliferone glucuronide respectively. Protein expression and localization were detected by immunoblot and immunohistochemistry. All statistics were non-parametric. RESULTS: UGT, beta-glucuronidase and CYP1A activities were detected in all placentas sampled; CYP2E1 was undetectable. CYP1A, UGT1A UGT2B, proteins were detected in all placentas (n = 6) tested and CYP2E1 in 4/6 placentas sampled and were localized to the syncytium. UGT and CYP1A activities were significantly elevated in the placentas of mothers who smoked (P <0.05 and P <0.001 respectively) and were greatest in women who both smoked and drank-alcohol (P <0.05 and P <0.01 respectively). Enzyme activities were significantly negatively correlated with gestational age (P <0.05, r = 0.54, UGT) and maternal age respectively (P <0.001, r = 0.63, CYP1A). beta-Glucuronidase activity did not differ with patient variables. CONCLUSIONS: Metabolism of compounds by the human placenta in the first trimester may be affected by maternal and environmental factors altering the activity of constitutive metabolizing enzymes.
U2 - 10.1093/humrep/17.10.2564
DO - 10.1093/humrep/17.10.2564
M3 - Article
VL - 17
SP - 2564
EP - 2572
JO - Human Reproduction
JF - Human Reproduction
SN - 0268-1161
ER -