Current understanding of autophagy in intrahepatic cholestasis of pregnancy

• Published in: Placenta (Eastbourne) 2021-11, Vol.115, p.53-59
• Main Authors: Shan, Dan, Dong, Ruihong, Hu, Yayi
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Autophagy - physiology; Bile Acids and Salts - physiology; Cholestasis, Intrahepatic - complications; Cholestasis, Intrahepatic - physiopathology; Diabetes, Gestational; Endoplasmic Reticulum Stress - physiology; Female; Fetal Death; Fetal Growth Retardation; Humans; Immunity; Inflammation; Intrahepatic cholestasis of pregnancy; Pre-Eclampsia; Pregnancy; Pregnancy Complications - physiopathology; Reactive Oxygen Species - metabolism; Risk Factors; Ursodeoxycholic Acid - physiology
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2021.09.014

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease during pregnancy. Manifested with pruritus and elevation in bile acids, the etiology of ICP is still poorly understood. Although ICP is considered relatively benign for the mother, increased rates of adverse fetal outcomes including sudden fetal demise are possible devastating outcomes associated with ICP. Limited understanding of the underlying mechanisms restricted treatment options and managements of ICP. In recent decades, evolving evidence indicated the significance of autophagy in pregnancy and pregnancy complications. Autophagy is an ancient self-defense mechanism which is essential for cell survival, differentiation and development. Autophagy has pivotal roles in embryogenesis, implantation, and maintenance of pregnancy, and is involved in the orchestration of diverse physiological and pathological cellular responses in patients with pregnancy complications. Recent advances in these research fields provide tantalizing targets on autophagy to improve the care of pregnant women. This review summarizes recent advances in understanding autophagy in ICP and its possible roles in the causation and prevention of ICP. •Hydrophobic bile acids are increased in ICP.•Autophagy is important in the pathogenesis of pregnancy complications.•Upstream regulators of autophagy are impaired in cholestasis.•Bile acids cause disruptions in ROS, ER stress, immune and inflammatory reactions.•UDCA's rebalancing function of autophagic responses bring benefits in ICP.