Maternal cholestasis during pregnancy programs metabolic disease in offspring

Georgia Papacleovoulou; Shadi Abu-Hayyeh; Evanthia Nikolopoulou; Oscar Briz; Bryn M Owen; Vanya Nikolova; Caroline Ovadia; Xiao Huang; Marja Vaarasmaki; Marc Baumann; Eugene Jansen; Christiane Albrecht; Marjo-Riitta Jarvelin; Jose J G Marin; A S Knisely; Catherine Williamson

doi:10.1172/JCI68927

Maternal cholestasis during pregnancy programs metabolic disease in offspring

Georgia Papacleovoulou, Shadi Abu-Hayyeh, Evanthia Nikolopoulou, Oscar Briz, Bryn M Owen, Vanya Nikolova, Caroline Ovadia, Xiao Huang, Marja Vaarasmaki, Marc Baumann, Eugene Jansen, Christiane Albrecht, Marjo-Riitta Jarvelin, Jose J G Marin, A S Knisely, Catherine Williamson

Women & Children's Health

Research output: Contribution to journal › Article › peer-review

98 Citations (Scopus)

Abstract

The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.

Original language	English
Pages (from-to)	3172-3181
Number of pages	10
Journal	Journal of Clinical Investigation
Volume	123
Issue number	7
DOIs	https://doi.org/10.1172/JCI68927
Publication status	Published - 1 Jul 2013

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10.1172/JCI68927

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Papacleovoulou, G., Abu-Hayyeh, S., Nikolopoulou, E., Briz, O., Owen, B. M., Nikolova, V., Ovadia, C., Huang, X., Vaarasmaki, M., Baumann, M., Jansen, E., Albrecht, C., Jarvelin, M.-R., Marin, J. J. G., Knisely, A. S., & Williamson, C. (2013). Maternal cholestasis during pregnancy programs metabolic disease in offspring. Journal of Clinical Investigation, 123(7), 3172-3181. https://doi.org/10.1172/JCI68927

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title = "Maternal cholestasis during pregnancy programs metabolic disease in offspring",

abstract = "The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.",

author = "Georgia Papacleovoulou and Shadi Abu-Hayyeh and Evanthia Nikolopoulou and Oscar Briz and Owen, {Bryn M} and Vanya Nikolova and Caroline Ovadia and Xiao Huang and Marja Vaarasmaki and Marc Baumann and Eugene Jansen and Christiane Albrecht and Marjo-Riitta Jarvelin and Marin, {Jose J G} and Knisely, {A S} and Catherine Williamson",

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Papacleovoulou, G , Abu-Hayyeh, S, Nikolopoulou, E, Briz, O, Owen, BM, Nikolova, V , Ovadia, C, Huang, X, Vaarasmaki, M, Baumann, M, Jansen, E, Albrecht, C, Jarvelin, M-R, Marin, JJG, Knisely, AS & Williamson, C 2013, 'Maternal cholestasis during pregnancy programs metabolic disease in offspring', Journal of Clinical Investigation, vol. 123, no. 7, pp. 3172-3181. https://doi.org/10.1172/JCI68927

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T1 - Maternal cholestasis during pregnancy programs metabolic disease in offspring

AU - Papacleovoulou, Georgia

AU - Abu-Hayyeh, Shadi

AU - Nikolopoulou, Evanthia

AU - Briz, Oscar

AU - Owen, Bryn M

AU - Nikolova, Vanya

AU - Ovadia, Caroline

AU - Huang, Xiao

AU - Vaarasmaki, Marja

AU - Baumann, Marc

AU - Jansen, Eugene

AU - Albrecht, Christiane

AU - Jarvelin, Marjo-Riitta

AU - Marin, Jose J G

AU - Knisely, A S

AU - Williamson, Catherine

PY - 2013/7/1

Y1 - 2013/7/1

N2 - The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.

AB - The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.

U2 - 10.1172/JCI68927

DO - 10.1172/JCI68927

M3 - Article

C2 - 23934127

SN - 0021-9738

VL - 123

SP - 3172

EP - 3181

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 7

ER -

Maternal cholestasis during pregnancy programs metabolic disease in offspring

Abstract

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