Intra-uterine growth restriction is associated with increased apoptosis and altered expression of proteins in the p53 pathway in villous trophoblast
Intra-uterine growth restriction is associated with increased apoptosis and altered expression of proteins in the p53 pathway in villous trophoblast
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DOI：
10.1007/s10495-010-0551-3
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发表时间：
2011-02-01
期刊：
影响因子：
7.2
通讯作者：
Crocker, Ian P.
中科院分区：
文献类型：
--
作者：
Heazell, Alexander E. P.;Sharp, Andrew N.;Crocker, Ian P.
宫内生长受限(IUGR)影响3-8%的妊娠，并与绒毛滋养层细胞周转改变有关，绒毛滋养层是人类胎盘的一种基本功能细胞类型。细胞凋亡的内在途径，尤其是P53，在调节胎盘细胞对损伤的反应中起着重要作用。我们推测胎儿宫内发育迟缓胎盘组织中P53途径的蛋白表达会发生改变。采用实时定量聚合酶链式反应、Western blotting和免疫组织化学方法检测P53通路成分的表达。IUGR中P53基因和蛋白表达增强，定位于合体滋养层细胞。P21和Bax的表达也发生了类似的变化。MDM2、Bak、Bcl2的表达无明显变化。IUGR中滋养层细胞周转改变和P53表达增加之间的关联让人想起暴露在低氧下。这些观察结果为IUGR的潜在发病机制提供了进一步的洞察力。P53及其在IUGR发病机制中的作用和相互作用还需要进一步的研究。
Intrauterine growth restriction (IUGR) affects 3-8% of pregnancies and is associated with altered cell turnover in the villous trophoblast, an essential functional cell type of the human placenta. The intrinsic pathway of apoptosis, particularly p53, is important in regulating placental cell turnover in response to damage. We hypothesised that expression of proteins in the p53 pathway in placental tissue would be altered in IUGR. Expression of constituents of the p53 pathway was assessed using real-time PCR, Western blotting and immunohistochemistry. p53 mRNA and protein expression was increased in IUGR, which localised to the syncytiotrophoblast. Similar changes were noted in p21 and Bax expression. There was no change in the expression of Mdm2, Bak and Bcl-2. The association between altered trophoblast cell turnover in IUGR and increased p53 expression is reminiscent of that following exposure to hypoxia. These observations provide further insight into the potential pathogenesis of IUGR. Further research is required to elicit the role and interactions of p53 and its place in the pathogenesis of IUGR.