Skip to ContentSkip to Navigation
About us Medical Sciences 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.

Authors:

  • 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; https://doi.org/10.1038/s41390-022-02303-5

Last modified:26 September 2022 08.13 a.m.

More news

  • 14 February 2023

    Lift to the inclusive workplace

    There is plenty of work, and yet people with a disability are still often sidelined. One plus one is two, or so you’d think: this is the perfect time to help this group of workers find a job. The intention is there, also within the University, but...

  • 15 December 2022

    Groningen contributes to major research initiative into energy-efficient information technology

    The Dutch science funding agency NWO recently awarded a large research project into new concepts for energy-efficient information technology of no less than ten million euros

  • 05 December 2022

    Frans J. Sijtsma new Director Agricola School

    On the recommendation of the Board of the University of Groningen, Dr Frans J. Sijtsma has been appointed as academic director of the Rudolf Agricola School for Sustainable Development with effect from 1 February 2023. This concerns a 0.5 FTE...