Kudo Yoshiki, Boyd C A R, Sargent I L, Redman C W G
Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, OX1 3QX, Oxford, UK.
Biochim Biophys Acta. 2003 May 20;1638(1):63-71. doi: 10.1016/s0925-4439(03)00043-7.
The fundamental process of placental trophoblast cell fusion (syncytiotrophoblast formation or syncytialisation) which is a characteristic of this tissue is poorly understood. Pre-eclampsia is associated with placental hypoxia and suppressed syncytiotrophoblast formation. We therefore have studied the effect of low-oxygen tensions on the rate of cell fusion, relative abundance of mRNAs encoding syncytin and its receptor, amino acid transport system B(0), which are thought to be involved in trophoblast cell fusion (as well as the activity of amino acid transport through this system) in a cell model of syncytialisation (BeWo cells following forskolin treatment). Forskolin-induced cell fusion (determined by a quantitative flow cytometry assay) was reversibly suppressed in 2% oxygen compared to 20% oxygen. This was associated with suppressed secretion of human chorionic gonadotropin. Forskolin stimulated relatively less syncytin mRNA (determined by reverse transcription-polymerase chain reaction) in 2% than in 20% oxygen and there was no stimulation after 48 h in 2% oxygen. There was a spontaneous, time-dependent increase of amino acid transporter B(0) mRNA in vehicle, which was suppressed by 2% oxygen and by forskolin treatment in 20% oxygen. Forskolin-induced changes in amino acid transport system B(0) function were not seen in cells cultured for 48 h in 2% oxygen. These observations suggest that under conditions of low ambient oxygen, dysregulation of expression of syncytin and of its receptor may suppress the normal process of cell fusion necessary for syncytiotrophoblast formation and contributes to syncytiotrophoblast abnormalities characteristic of pre-eclampsia.
胎盘滋养层细胞融合(合体滋养层细胞形成或合体化)这一该组织特有的基本过程目前仍知之甚少。子痫前期与胎盘缺氧及合体滋养层细胞形成受抑制有关。因此,我们在一个合体化细胞模型( Forskolin处理后的BeWo细胞)中研究了低氧张力对细胞融合速率、编码合胞素及其受体、氨基酸转运系统B(0)的mRNA相对丰度的影响,这些被认为与滋养层细胞融合有关(以及通过该系统的氨基酸转运活性)。与20%氧气条件相比,在2%氧气条件下, Forskolin诱导的细胞融合(通过定量流式细胞术测定)受到可逆性抑制。这与人类绒毛膜促性腺激素分泌受抑制有关。与20%氧气条件相比,在2%氧气条件下, Forskolin刺激产生的合胞素mRNA相对较少(通过逆转录-聚合酶链反应测定),且在2%氧气条件下48小时后无刺激作用。在无药物处理的情况下,氨基酸转运体B(0) mRNA有自发的、时间依赖性增加,在2%氧气条件下以及在20%氧气条件下经Forskolin处理后受到抑制。在2%氧气条件下培养48小时的细胞中未观察到Forskolin诱导的氨基酸转运系统B(0)功能变化。这些观察结果表明,在低环境氧条件下,合胞素及其受体表达失调可能会抑制合体滋养层细胞形成所必需的正常细胞融合过程,并导致子痫前期特有的合体滋养层细胞异常。