Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption
Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption
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DOI：
10.1093/humrep/17.10.2564
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发表时间：
2002-10-01
影响因子：
6.1
通讯作者：
Keelan, JA
中科院分区：
文献类型：
--
作者：
Collier, AC;Tingle, MD;Keelan, JA
背景技术：本研究的基本原理是评估酶尿苷二磷酸葡萄糖醛酸转移酶（UGT）、β-葡萄糖醛酸苷酶、细胞色素P450 1A（CYP 1A）和细胞色素P4590 2 E1（CYP 2 E1）在妊娠早期人胎盘中的表达、活性和定位，并评估母体变量对胎盘代谢的影响。分别用乙氧基试卤灵、氯唑沙宗、4-甲基伞形酮和4-甲基伞形酮葡萄糖醛酸苷测定25例胎盘的CYP 1A、CYP 2 E1、UGT和β-葡萄糖醛酸酶活性。免疫印迹和免疫组化检测蛋白表达和定位。所有统计均为非参数。结果：UGT、β-葡萄糖醛酸酶和CYP 1A活性在所有采样的胎盘中检测到; CYP 2 E1未检测到。在所有检测的胎盘（n = 6）中检测到CYP 1A、UGT 1A和UGT 2B蛋白，在4/6个采样的胎盘中检测到CYP 2 E1，并定位于合胞体。吸烟组胎盘UGT和CYP 1A活性显著升高（P < 0.05和P < 0.001），吸烟和饮酒组最高（P < 0.05和P < 0.01）。酶活性与孕龄（P < 0.05，r = 0.54，UGT）和母亲年龄（P < 0.001，r = 0.63，CYP 1A）呈显著负相关。β-葡萄糖醛酸酶活性与患者变量无差异。结论：妊娠早期胎盘对化合物的代谢可能受到母体和环境因素的影响，这些因素改变了组成型代谢酶的活性。
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.