Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption

被引:88
作者
Collier, AC
Tingle, MD
Paxton, JW
Mitchell, MD
Keelan, JA
机构
[1] Univ Auckland, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand
[2] Univ Auckland, Liggins Inst, Auckland 1, New Zealand
关键词
alcohol consumption; CYP1A; placental metabolism; smoking; UDP-glucuronosyltransferase;
D O I
10.1093/humrep/17.10.2564
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
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.
引用
收藏
页码:2564 / 2572
页数:9
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