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Research Pediatrics
University Medical Center Groningen

New Key Publication: Perinatal exposure to UDCA prevents neonatal cholestasis in Cyp2c70-/- mice with human-like bile acids

23 September 2022

BACKGROUND: Cyp2c70-/- mice with a human-like bile acid (BA) composition display features of neonatal cholestasis. We assessed whether perinatal ursodeoxycholic acid (UDCA) exposure prevents neonatal cholestasis in Cyp2c70-/- mice and reduces cholangiopathy development later in life.

METHODS: Cyp2c70+/- males were crossed with Cyp2c70+/- females fed either a regular chow diet or a 0.1% UDCA-containing diet during breeding, gestation, and suckling. Cholestasis and liver function parameters were assessed in their Cyp2c70-/- and wild-type offspring at 3 and 8 weeks of age.

RESULTS: Three-week-old Cyp2c70-/- pups showed features of neonatal cholestasis, including elevated plasma BAs and transaminases, which were completely prevented in Cyp2c70-/- pups upon perinatal UDCA exposure. In addition, UDCA administration to the dams corrected altered hepatic gene expression patterns in Cyp2c70-/- pups, reduced markers of fibrogenesis and inflammation, and prevented cholangiocyte proliferation. Yet, these beneficial effects of perinatal UDCA exposure were not retained into adulthood upon discontinuation of treatment.

CONCLUSION: Perinatal exposure of Cyp2c70-/- mice to UDCA has beneficial effects on liver function parameters, supporting a direct role of BA hydrophobicity in the development of neonatal cholestasis in these mice. However, prevention of neonatal cholestasis in Cyp2c70-/- mice has no long-lasting effects on liver pathophysiology.


  • Hilde D. de Vries
  • Anna Palmiotti
  • Rumei Li
  • Milaine V. Hovingh
  • Niels L. Mulder
  • Martijn Koehorst
  • Vincent W. Bloks
  • Tim van Zutphen
  • Folkert Kuipers
  • Jan Freark de Boer

Read more: Pediatric Research;

Last modified:26 September 2022 08.13 a.m.

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