title: Placental profiling of UGT1A enzyme expression and activity and interactions with preeclampsia at term.
abstract: Placental UDP-glucuronosyltransferase (UGT) enzymes have critical roles in hormone, nutrient, chemical balance and fetal exposure during pregnancy. Placental UGT1A isoforms were profiled and differences between preeclamptic (PE) and non-PE placental UGT expression determined. In third trimester villous placenta, UGT1A1, 1A4, 1A6 and 1A9 were expressed and active in all specimens (n = 10), but UGT1A3, 1A5, 1A7, 1A8 and 1A10 were absent. The UGT1A activities were comparable to human liver microsomes per milligram, but placental microsome yields were only 2 % of liver (1 mg/g of tissue vs. 45 mg/g of tissue). For successful PCR, placental collection and processing within 60 min from delivery, including DNAse and ≥300 ng of RNA in reverse transcription were essential and snap freezing in liquid nitrogen immediately was the best preservation method. Although UGT1A6 mRNA was lower in PE (P < 0.001), there were no other significant effects on UGT mRNA, protein or activities. A more comprehensive tissue sample set is required for confirmation of PE interactions with UGT. Placental UGT1A enzyme expression patterns are similar to the liver and a detoxicative role for placental UGT1A is inferred.
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI, 96813, USA. abby.collier@ubc.ca.|Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. abby.collier@ubc.ca.
authors.forename: Abby C
authors.initials: AC
authors.lastname: Collier
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI, 96813, USA.
authors.forename: Audrey D
authors.initials: AD
authors.lastname: Thévenon
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, Kapi'olani Medical Center for Women and Children, 1319 Punahou Street, Honolulu, HI, 96826, USA.
authors.forename: William
authors.initials: W
authors.lastname: Goh
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, Kapi'olani Medical Center for Women and Children, 1319 Punahou Street, Honolulu, HI, 96826, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hiraoka
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, Kapi'olani Medical Center for Women and Children, 1319 Punahou Street, Honolulu, HI, 96826, USA.|Division of Natural Sciences and Mathematics, Chaminade University of Honolulu, 3140 Waialae Avenue, Honolulu, HI, 96816, USA.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Kendal-Wright
mesh_terms: D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D010920:Placenta / Q000201:enzymology* / Q000473:pathology; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D011247:Pregnancy; D047929:Term Birth / Q000378:metabolism*; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
keywords: Developmental pharmacology; Glucuronidation; Obstetrics; Phase II metabolism