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Human Reproduction, Vol. 17, No. 10, 2564-2572, October 2002
© 2002 European Society of Human Reproduction and Embryology

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

Abby C. Collier1,2,3, Malcolm D. Tingle1, James W. Paxton1, Murray D. Mitchell1,2 and Jeffrey A. Keelan1,2

1 Department of Pharmacology & Clinical Pharmacology and 2 The Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand

BACKGROUND: The rationale for this study was to assess the expression, activity and localization of the enzymes uridine diphosphate glucuronosyltransferase (UGT), ß-glucuronidase, cytochrome P450 1A (CYP1A) and cytochrome P450 2E1 (CYP2E1) in first trimester human placenta and to gauge the effects of maternal variables on placental metabolism. METHODS: CYP1A, CYP2E1, UGT and ß-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, ß-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). ß-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.

Key words: alcohol consumption/CYP1A/placental metabolism/smoking/UDP-glucuronosyltransferase

3 To whom correspondence should be addressed at: Department of Nutrition, MS 199, University of Nevada, Reno, NV 89557, USA. E-mail: abbyc{at}unr.edu


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