Mechanism of mitochondrial dysfunction on placental trophoblastic cells in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterized by elevated serum bile acids and adverse fetal outcomes. Elevated bile acids can lead to excessive accumulation of reactive oxygen species (ROS) in the placenta, and high ROS levels can cause mitochondrial damage. This study primarily investigates the mechanisms of bile acid-induced mitochondrial dysfunction to provide precise targets for the treatment of ICP. Single-cell sequencing of human placental tissues was conducted to analyze changes in mitochondrial function of ICP placental trophoblasts. An ICP cell model was established using TCA, and the effects of TCA on trophoblast mitochondrial function were observed through detection of ROS, mitochondrial membrane potential, fluorescence confocal microscopy, and other methods. Single-cell sequencing indicated significant impairment of mitochondrial function in ICP placental trophoblasts, and electron microscopy results also suggested severe damage to the mitochondrial structure of ICP placental trophoblasts. Both the morphology and function of mitochondria in the ICP cell model were significantly altered, possibly due to impaired mitochondrial transcription mechanisms mediated by NRF1/PGC-1α pathway. Elevated serum bile acids in ICP pregnant women may lead to mitochondrial damage in placental trophoblasts through the NRF1/PGC-1α pathway, thereby affecting the function of placental trophoblasts.