Nuclear receptor-driven alterations in bile acid and lipid metabolic pathways during gestation

Nuclear receptor signalling is essential for physiological processes such as metabolism, development, and reproduction. Alterations in the endocrine state that naturally occur during pregnancy result in maternal adaptations to support the feto-placental unit. A series of studies have shown that nuclear receptor signalling is involved in maternal adaptations of bile acid, cholesterol, and lipid homeostasis pathways to ensure maintenance of the nutritional demands of the fetus. We discuss regulation of hepatic nuclear receptors and their target genes in pregnancy and their impact on the development of disorders such as intrahepatic cholestasis of pregnancy and oestrogen-induced hepatotoxicity. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.

Research Highlights
► Altered nuclear receptor signalling is part of the maternal hepatic adaptations that occur during pregnancy.
► Intrahepatic cholestasis and oestrogen-induced hepatotoxicity in pregnancy have been shown to be associated with reduced FXR and PPAR-α activity.
► Agonists of FXR and PPAR-α signalling pathways are of potential therapeutic benefit to treat metabolic pregnancy disorders.