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Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy

Luiza Borges Manna1, Georgia Papacleovoulou1, Flavia Flaviani1,2

  • 1Division of Women and Children's Health, King's College London, London, United Kingdom.

Scientific Reports
|June 27, 2020
PubMed

Insights

Intrahepatic cholestasis of pregnancy (ICP) can harm offspring metabolic health. Ursodeoxycholic acid (UDCA) treatment during pregnancy improved fetal lipid profiles and adult offspring glucose tolerance in a mouse model, suggesting a protective role.

Area of Science:

  • Perinatology
  • Metabolic Health
  • Pharmacology

Background:

  • Intrauterine environment perturbations impact lifelong metabolic health.
  • Intrahepatic cholestasis of pregnancy (ICP) is linked to offspring metabolic disease due to factors like elevated bile acids and dyslipidemia.
  • Ursodeoxycholic acid (UDCA) treats ICP, but its preventative effects on offspring metabolic consequences are unknown.

Purpose of the Study:

  • To investigate if UDCA can prevent the metabolic effects of ICP in the offspring and fetoplacental unit.
  • To analyze the impact of UDCA on fetal lipid profiles in ICP pregnancies.
  • To evaluate UDCA's effects on fetal liver function, gene expression, and adult offspring metabolic health in a mouse model.

Main Methods:

  • Analysis of fetal serum lipid profiles in human pregnancies (untreated ICP, UDCA-treated ICP, uncomplicated).
  • Utilized a mouse model of hypercholanemic pregnancy to study UDCA effects.
  • Assessed hepatoprotective mechanisms, hepatic fatty acid synthase (Fas) expression, glucose tolerance, and epigenetic changes in offspring.

Main Results:

  • UDCA ameliorated ICP-associated fetal dyslipidemia in human pregnancies.
  • In a mouse model, UDCA induced fetal liver hepatoprotective mechanisms and reduced hepatic Fas expression.
  • UDCA treatment improved glucose tolerance in adult offspring and revealed relevant epigenetic changes.

Conclusions:

  • UDCA demonstrates potential in ameliorating fetal dyslipidemia associated with ICP.
  • UDCA treatment during pregnancy may protect the fetal liver and improve offspring metabolic health.
  • UDCA can be considered an intervention to mitigate metabolic disease features in offspring of mothers with hypercholanemic conditions.

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