title: Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy.
abstract: OBJECTIVE
  Intrahepatic cholestasis of pregnancy (ICP) is complicated by spontaneous preterm labor, fetal anoxia and unexplained fetal death. We aim to evaluate the mechanisms by which raised fetal bile acids cause placental abnormalities and fetal cardiac pathology.
  
  
  METHODS
  The study was performed using placental samples taken from ICP pregnancies, placental explant culture, neonatal and adult cardiomyocytes, and murine and human embryonic stem cell-derived cardiomyocytes.
  
  
  RESULTS
  Maternal cholestasis causes a placental phenotype with histological abnormalities. This can be evaluated using placental explant cultures. Taurocholate, the principal bile acid raised in the fetal compartment in ICP, causes abnormal cardiomyocyte contraction, rhythm and desynchronization of calcium dynamics. To extend our observations that the muscarinic M2 receptor plays a role in bile acid-induced arrhythmia in cardiomyocytes, we are developing a model containing mixed cell populations to represent the fetal and maternal hearts. This will be used to evaluate the underlying mechanisms to explain fetal arrhythmia in the presence of cholestasis.
  
  
  CONCLUSIONS
  Bile acids signal via a spectrum of pathways in the placenta and the fetal heart.
authors.affiliation: Institute of Reproductive and Developmental Biology, National Heart and Lung Institute, Imperial College London, London, UK. catherine.williamson@imperial.ac.uk
authors.forename: Catherine
authors.initials: C
authors.lastname: Williamson
authors.forename: Michele
authors.initials: M
authors.lastname: Miragoli
authors.forename: Siti
authors.initials: S
authors.lastname: Sheikh Abdul Kadir
authors.forename: Shadi
authors.initials: S
authors.lastname: Abu-Hayyeh
authors.forename: Georgia
authors.initials: G
authors.lastname: Papacleovoulou
authors.forename: Victoria
authors.initials: V
authors.lastname: Geenes
authors.forename: Julia
authors.initials: J
authors.lastname: Gorelik
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism*; D002780:Cholestasis, Intrahepatic / Q000378:metabolism*; D005260:Female; D005318:Fetal Heart; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001647:Bile Acids and Salts