ABSTRACT
Genes from Ugt1a family in placenta and fetal liver are responsible for hormone, nutrient and chemical balance during pregnancy. Assisted reproduction technologies (ART) i.e. intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) alter steroid homeostasis in pregnancy through increased glucuronidation. Here we show that ART (particularly ICSI) upregulates Ugt1a1, 1a2, 1a6 and 1a9 expression in murine placentas and fetal livers with higher mRNA related to lower progesterone (1a1) and cholesterol (1a2, 1a6) in placentas. Greater steroid clearance in ART through transcriptional upregulation of Ugt1a in the placental-fetal unit may decrease the availability of essential molecules, mediating negative reproductive outcomes.
Subject(s)
Fertilization in Vitro , Glucuronosyltransferase/metabolism , Infertility, Female/metabolism , Liver/metabolism , Placenta/metabolism , Pregnancy Proteins/metabolism , Sperm Injections, Intracytoplasmic , Animals , Cholesterol/metabolism , Crosses, Genetic , Disease Models, Animal , Female , Glucuronosyltransferase/genetics , Infertility, Female/enzymology , Infertility, Female/therapy , Isoenzymes/genetics , Isoenzymes/metabolism , Liver/embryology , Liver/enzymology , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Placenta/enzymology , Pregnancy , Pregnancy Proteins/genetics , Progesterone/metabolism , UDP-Glucuronosyltransferase 1A9 , Up-RegulationABSTRACT
OBJECTIVE: We undertook this study to assess the agreement between fetal umbilical cord drug levels and maternal self-report. STUDY DESIGN: Cord samples were collected from 103 placentas after delivery as a subproject of the larger Pacific Research Center for Early Human Development (PRCEHD) study. These cord samples were then processed to obtain cord lysates and enzyme-linked immunosorbent assay (ELISA) performed for cotinine and illicit drugs. Levels of each of these substances were compared with clinical information. RESULT: We found fair agreement between self-reported smoking and cotinine levels (κ = 0.26 (0.07 to 0.5)) as well as slight agreement with current drug use and positive drug levels (κ = 0.19 (-0.05 to 0.4)). Compared with maternal self-report, sensitivity of cotinine levels was 27% and specificity was 98%. Sensitivity of positive cord illicit drug levels was 32% and specificity was 85%. CONCLUSION: Umbilical cords provide another independent measure of maternal drug use and are readily available. To our knowledge, this is the first study to measure cotinine levels in the umbilical cord tissue.
