Institute of Reproductive and Developmental Biology, Imperial College London, Du Cane Road, London W12 0NN, UK.
Placenta. 2011 Dec;32(12):1026-32. doi: 10.1016/j.placenta.2011.09.006. Epub 2011 Oct 20.
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease associated with significant risk of fetal complications. It is hypothesised that the risk of adverse fetal outcomes relates to the toxic effects of bile acids, the levels of which are increased in both maternal and fetal serum. Human and rodent studies have shown that transplacental transfer of bile acids is impaired in ICP. Furthermore, the morphology of placentas from the rodent model of ICP is markedly abnormal, and is associated with increased expression of apoptotic markers and oxidative stress. Using placental tissue from ICP cases and normal pregnancies and cultured placental explant fragments we investigated the histological and molecular effects of cholestasis. We also examined the influence of ursodeoxycholic acid (UDCA) administration on these parameters. Here we report that ICP is associated with several morphological abnormalities of the placenta, including an increase in the number of syncytial knots, and that these can be reproduced in an in vitro (explant) model exposed to the bile acids taurocholic acid and taurochenodoexycholic acid. Furthermore, we demonstrate that ursodeoxycholic acid, a drug commonly used in the management of ICP, has a protective effect on placental tissue both in vivo and in vitro.
妊娠肝内胆汁淤积症（ICP）是一种与胎儿并发症显著相关的妊娠特有肝脏疾病。据推测，不良胎儿结局的风险与胆汁酸的毒性作用有关，其在母血和胎血中的水平均升高。人体和啮齿动物研究表明，ICP 中胆汁酸的胎盘转运受损。此外，ICP 啮齿动物模型的胎盘形态明显异常，与凋亡标志物表达增加和氧化应激有关。我们使用来自 ICP 病例和正常妊娠的胎盘组织以及培养的胎盘碎片，研究了胆汁淤积的组织学和分子影响。我们还检查了熊去氧胆酸（UDCA）给药对这些参数的影响。本研究报告称，ICP 与胎盘的几种形态异常有关，包括合胞体结节数量增加，并且这些异常可在体外（培养物）模型中重现，该模型暴露于胆酸牛磺胆酸和牛磺鹅脱氧胆酸。此外，我们证明熊去氧胆酸是一种常用于 ICP 治疗的药物，对体内和体外的胎盘组织均具有保护作用。
