Bile acid signaling in fetal tissues

Implications for intrahepatic cholestasis of pregnancy

Catherine Williamson, Michele Miragoli, Siti Sheikh Abdul Kadir, Shadi Abu-Hayyeh, Georgia Papacleovoulou, Victoria Geenes, Julia Gorelik

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background/Aims: 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. Conclusion: Bile acids signal via a spectrum of pathways in the placenta and the fetal heart.

Original languageEnglish
Pages (from-to)58-61
Number of pages4
JournalDigestive Diseases
Volume29
Issue number1
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Bile Acids and Salts
Cardiac Myocytes
Fetus
Fetal Heart
Cholestasis
Cardiac Arrhythmias
Mothers
Fetal Hypoxia
Muscarinic M2 Receptors
Taurocholic Acid
Fetal Death
Premature Obstetric Labor
Placenta
Pathology
Calcium
Phenotype
Pregnancy
Intrahepatic Cholestasis of Pregnancy
Population

Keywords

  • Arrhythmia
  • Bile acid
  • Cholestasis
  • Fetus
  • Placenta

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Williamson, C., Miragoli, M., Sheikh Abdul Kadir, S., Abu-Hayyeh, S., Papacleovoulou, G., Geenes, V., & Gorelik, J. (2011). Bile acid signaling in fetal tissues: Implications for intrahepatic cholestasis of pregnancy. Digestive Diseases, 29(1), 58-61. https://doi.org/10.1159/000324130

Bile acid signaling in fetal tissues : Implications for intrahepatic cholestasis of pregnancy. / Williamson, Catherine; Miragoli, Michele; Sheikh Abdul Kadir, Siti; Abu-Hayyeh, Shadi; Papacleovoulou, Georgia; Geenes, Victoria; Gorelik, Julia.

In: Digestive Diseases, Vol. 29, No. 1, 06.2011, p. 58-61.

Research output: Contribution to journalArticle

Williamson, C, Miragoli, M, Sheikh Abdul Kadir, S, Abu-Hayyeh, S, Papacleovoulou, G, Geenes, V & Gorelik, J 2011, 'Bile acid signaling in fetal tissues: Implications for intrahepatic cholestasis of pregnancy', Digestive Diseases, vol. 29, no. 1, pp. 58-61. https://doi.org/10.1159/000324130
Williamson C, Miragoli M, Sheikh Abdul Kadir S, Abu-Hayyeh S, Papacleovoulou G, Geenes V et al. Bile acid signaling in fetal tissues: Implications for intrahepatic cholestasis of pregnancy. Digestive Diseases. 2011 Jun;29(1):58-61. https://doi.org/10.1159/000324130
Williamson, Catherine ; Miragoli, Michele ; Sheikh Abdul Kadir, Siti ; Abu-Hayyeh, Shadi ; Papacleovoulou, Georgia ; Geenes, Victoria ; Gorelik, Julia. / Bile acid signaling in fetal tissues : Implications for intrahepatic cholestasis of pregnancy. In: Digestive Diseases. 2011 ; Vol. 29, No. 1. pp. 58-61.
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