Martineau M, Papacleovoulou G, Abu-Hayyeh S, Dixon P H, Ji H, Powrie R, Larson L, Chien E K, Williamson C
Maternal and Fetal Disease Group, Institute of Reproductive and Developmental Biology, Imperial College London, UK; Division of Obstetric & Consultative Medicine, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
Maternal and Fetal Disease Group, Institute of Reproductive and Developmental Biology, Imperial College London, UK; Women's Health Academic Centre, Kings College London, 2nd Floor Hodgkin Building, Guy's campus, London, UK.
Placenta. 2014 Jan;35(1):37-43. doi: 10.1016/j.placenta.2013.10.019. Epub 2013 Nov 7.
Intrahepatic Cholestasis of Pregnancy (ICP) is associated with an increased risk of fetal morbidity and mortality and is characterised by elevated bile acids in the maternal and fetal compartments. Bile acids have been shown to attenuate renal 11βHSD2 expression and, given the protective role of placental 11βHSD2 in preventing fetal exposure to excessive maternal cortisol, we aimed to establish whether raised serum bile acids in ICP influence placental 11βHSD2 expression.
Placental tissue from human and murine cholestatic pregnancy was evaluated for changes in 11βHSD2 mRNA expression compared to uncomplicated pregnancy using quantitative PCR. Parallel in vitro studies were performed using BeWo choriocarcinoma cells to assess the effect of different bile acid species on 11βHSD2 gene expression and whether concurrent UDCA administration can reverse any bile acid induced changes.
Placental 11βHSD2 mRNA expression was reduced in human and murine cholestatic pregnancy. In BeWo cells, treatment with the primary bile acid CDCA resulted in reduced 11βHSD2 gene expression, while treatment with other primary bile acids had no significant effect. Furthermore, the tertiary bile acid UDCA, used in the treatment of ICP did not significantly affect 11βHSD2 mRNA levels either alone, or when co-administered with CDCA.
Under cholestatic conditions placental 11βHSD2 mRNA is reduced. Studies in BeWo choriocarcinoma cells demonstrated that CDCA is likely to be the specific bile acid that mediates this effect. UDCA, the main bile acid used to treat cholestasis, did not reduce placental 11βHSD2 expression, further supporting its use in the management of ICP.
妊娠期肝内胆汁淤积症（ICP）与胎儿发病和死亡风险增加相关，其特征是母体和胎儿体内胆汁酸水平升高。胆汁酸已被证明会减弱肾脏11βHSD2的表达，鉴于胎盘11βHSD2在防止胎儿暴露于过量母体皮质醇方面的保护作用，我们旨在确定ICP中血清胆汁酸升高是否会影响胎盘11βHSD2的表达。
使用定量PCR评估来自人类和小鼠胆汁淤积性妊娠的胎盘组织与非复杂性妊娠相比11βHSD2 mRNA表达的变化。使用BeWo绒毛膜癌细胞进行平行的体外研究，以评估不同胆汁酸种类对11βHSD2基因表达的影响，以及同时给予熊去氧胆酸（UDCA）是否可以逆转任何胆汁酸诱导的变化。
在人类和小鼠胆汁淤积性妊娠中，胎盘11βHSD2 mRNA表达降低。在BeWo细胞中，用初级胆汁酸鹅去氧胆酸（CDCA）处理导致11βHSD2基因表达降低，而用其他初级胆汁酸处理则没有显著影响。此外，用于治疗ICP的次级胆汁酸UDCA单独使用或与CDCA共同使用时，均未显著影响11βHSD2 mRNA水平。
在胆汁淤积条件下，胎盘11βHSD2 mRNA减少。在BeWo绒毛膜癌细胞中的研究表明，CDCA可能是介导这种作用的特定胆汁酸。用于治疗胆汁淤积的主要胆汁酸UDCA不会降低胎盘11βHSD2的表达，这进一步支持了其在ICP管理中的应用。
