Okamoto A, Endo H, Kalionis B, Shinya M, Saito M, Nikaido T, Tanaka T
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Placenta. 2006 Feb-Mar;27(2-3):317-21. doi: 10.1016/j.placenta.2004.12.007.
To date, the clinicopathological features of intrauterine growth restriction (IUGR) are not clearly understood, and no effective therapy has been established for IUGR. This is the first study that uses microarray analysis to identify differentially expressed genes in the IUGR placenta. The expression profiles of a total of 9121 genes were examined by cDNA microarray analysis, using mRNA from an appropriate gestational age (AGA) placenta and an IUGR placenta from discordant dichorionic twins. Up-regulation of the IGFBP1 and Follistatin-like 3 genes was detected in the IUGR placenta, with a balanced differential degree of 20.7+/-1.3 and 13.1+/-2.1, respectively, while the balanced differential degrees of other genes were 2.6 or less. The expressions of the IGFBP1 and Follistatin-like 3 genes in four single IUGR and four AGA placentas were also examined by RT-PCR. Consistent with our data in discordant chorionic twin placentas, three of four IUGR placentas showed up-regulation of the IGFBP1 and all four IUGR placentas showed upregulation of Follistatin-like 3 genes when compared to the AGA placentas. Our results suggest that IGFBP1 and Follistatin-like 3 are highly up-regulated in IUGR in the placenta. IGFBP1 and Follistatin-like 3 are known critical regulators of fetal growth and differentiation. Pathways associated with these genes might be important for the pathogenesis of IUGR.
迄今为止,宫内生长受限(IUGR)的临床病理特征尚不清楚,且尚未建立针对IUGR的有效治疗方法。这是第一项使用微阵列分析来鉴定IUGR胎盘差异表达基因的研究。通过cDNA微阵列分析,使用来自适当孕周(AGA)胎盘和双绒毛膜双胎不一致的IUGR胎盘的mRNA,检测了总共9121个基因的表达谱。在IUGR胎盘中检测到IGFBP1和类卵泡抑素3基因上调,平衡差异度分别为20.7±1.3和13.1±2.1,而其他基因的平衡差异度为2.6或更低。还通过RT-PCR检测了四个单胎IUGR胎盘和四个AGA胎盘中IGFBP1和类卵泡抑素3基因的表达。与我们在双绒毛膜双胎胎盘的数据一致,与AGA胎盘相比,四个IUGR胎盘中有三个显示IGFBP1上调,所有四个IUGR胎盘均显示类卵泡抑素3基因上调。我们的结果表明,IGFBP1和类卵泡抑素3在IUGR胎盘组织中高度上调。IGFBP1和类卵泡抑素3是已知的胎儿生长和分化的关键调节因子。与这些基因相关的信号通路可能对IUGR的发病机制很重要。