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Maternal restraint stress during pregnancy in mice induces 11β-HSD1-associated metabolic changes in the livers of the offspring

  • H. Maeyama (a1), T. Hirasawa (a1) (a2), Y. Tahara (a1), C. Obata (a1) (a2), H. Kasai (a3), K. Moriishi (a3), K. Mochizuki (a4) and T. Kubota (a1)...


In rats, maternal exposure to restraint stress during pregnancy can induce abnormalities in the cardiovascular and central nervous systems of the offspring. These effects are mediated by long-lasting hyperactivation of the hypothalamic–pituitary–adrenal axis. However, little is known about the potential effects of stress during pregnancy on metabolic systems. We examined the effect of restraint stress in pregnant mice on the liver function of their offspring. The offspring of stressed mothers showed significantly higher lipid accumulation in the liver after weaning than did the controls; this accumulation was associated with increased expression of lipid metabolism-related proteins such as alanine aminotransferase 2 diglyceride acyltransferase 1, peroxisome proliferator-activated receptor gamma and glucocorticoid receptor. Additionally, we observed increased levels of 11β-hydroxysteroid dehydrogenase type 1, an intercellular mediator that converts glucocorticoid from the inactive to the active form, in the foetal and postnatal periods. These results indicate that restraint stress in pregnancy in mice induces metabolic abnormalities via 11β-hydroxysteroid dehydrogenase type 1-related pathways in the foetal liver. It is therefore possible that exposure to stress in pregnant women may be a risk factor for metabolic syndromes (e.g. fatty liver) in children.


Corresponding author

*Address for correspondence: T. Hirasawa, Department of Epigenetic Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. (Email


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Maternal restraint stress during pregnancy in mice induces 11β-HSD1-associated metabolic changes in the livers of the offspring

  • H. Maeyama (a1), T. Hirasawa (a1) (a2), Y. Tahara (a1), C. Obata (a1) (a2), H. Kasai (a3), K. Moriishi (a3), K. Mochizuki (a4) and T. Kubota (a1)...


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