Placental profiling of UGT1A enzyme expression and activity and interactions with preeclampsia at term

Eur J Drug Metab Pharmacokinet. 2015 Dec;40(4):471-80. doi: 10.1007/s13318-014-0243-4. Epub 2014 Dec 3.

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.

Keywords: Developmental pharmacology; Glucuronidation; Obstetrics; Phase II metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Female
  • Gene Expression Regulation, Enzymologic
  • Glucuronosyltransferase / biosynthesis*
  • Glucuronosyltransferase / genetics
  • Humans
  • Placenta / enzymology*
  • Placenta / pathology
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / enzymology*
  • Pre-Eclampsia / genetics
  • Pregnancy
  • Term Birth / metabolism*

Substances

  • UGT1A1 enzyme
  • Glucuronosyltransferase