Abstract: Objective To investigate the role of endoplasmic reticulum stress (ERS)- induced trophoblast apoptosis in the development of intrahepatic cholestasis during pregnancy (ICP). Methods Twenty pregnant women with ICP and 20 normal pregnant women undergoing cesarean section were enrolled in this study. The number of placenta syncytial knots in these women was determined using HE staining. The mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 were detected using RT-PCR in the placental tissues of the women and also in HTR-8/SVneo cells treated with different doses of deoxycholic acid (DCA). Caspase-3 and caspase-7 activities were also detected in DCA-treated HTR-8/SVneo cells using commercial assay kits, and the presence of apoptotic bodies in the cells were detected with electron microscopy. Results Compared with normal placental tissues, the placenta from women with ICP showed significantly increased syncytial knots (P<0.01) and obviously enhanced mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 (P<0.05). In HTR-8/SVneo cells treated with different doses of DCA (0, 10, 50, and 100 μmol/L), the mRNA expressions of GRP78, CHOP, caspase-3 and caspase-7 were significantly increased in a dose-dependent manner (P<0.05) and the protein levels of GRP78 and CHOP were also increased dosedependently. Treatment with DCA at 50 μmol/L for 24 h significantly upregulated caspase-3 and caspase-7 activity in the cells (P<0.05), and the cells treated with 50 μmol/L DCA for 12 h showed the presence of apoptotic bodies. Conclusion The activation of ERS and enhanced apoptosis of the trophoblasts occur in the placenta of women with ICP. DCA can significantly increase the expressions of ERS markers and thus lead to trophoblast apoptosis, suggesting that ERS- induced trophoblasts apoptosis may play a key role in the development of ICP.