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

Hum Reprod. 2002 Oct;17(10):2564-72. doi: 10.1093/humrep/17.10.2564.


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 P450 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alcohol Drinking / adverse effects*
  • Blotting, Western
  • Cytochrome P-450 CYP1A1 / analysis
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP1A2 / analysis
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP2E1 / analysis
  • Cytochrome P-450 CYP2E1 / metabolism
  • Female
  • Gestational Age*
  • Glucuronidase / analysis
  • Glucuronidase / metabolism
  • Glucuronosyltransferase / analysis
  • Glucuronosyltransferase / metabolism
  • Humans
  • Maternal Age*
  • Placenta / enzymology*
  • Pregnancy
  • Smoking / adverse effects*


  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • Glucuronosyltransferase
  • Glucuronidase