Kim Myung-Sun, Gu Bon-Hee, Song Sangjin, Choi Bum-Chae, Cha Dong-Hyun, Baek Kwang-Hyun
Department of Biomedical Science, CHA University, CHA General Hospital, 606-16 Yeoksam 1-Dong, Gangnam-Gu, Seoul 135-081, Korea.
Mol Biosyst. 2011 May;7(5):1430-40. doi: 10.1039/c0mb00219d. Epub 2011 Feb 18.
Recurrent pregnancy loss (RPL) is defined as at least three pregnancy losses in series prior to the 20-28 weeks of pregnancy. There are several etiological factors associated with immunology, anatomy, endocrinology, genetic, infection, chromosomal abnormalities, and environmental factors contributing to the condition. The aim of this study was to identify RPL associated factors in human blood using proteomics. Since it is difficult to obtain tissues or follicular fluids, we used blood samples from normal and RPL patients to conduct a comparative proteomic study. Three RPL blood samples and one cocktailed blood sample from 3 normal women were used. We performed 2-DE and selected spots were analyzed with MALDI-TOF/MS. In the three RPL blood samples, 2-DE analysis revealed 549, 563 and 533 spots to be differentially expressed, respectively. Through a comparative analysis between the control and RPL, 21 spots were shown to be differentially expressed. Of these, 5 proteins were confirmed by Western blot analysis. One of these proteins, ITI-H4 (inter-α trypsin inhibitor-heavy chain 4), was weakly expressed at a molecular weight of 120 kDa, but was highly expressed at a modified molecular weight of 36 kDa in RPL patients. These findings suggest that ITI-H4 expression may be used as a biomarker, which could facilitate the development of novel diagnostic and therapeutic tools.
复发性流产（RPL）的定义为妊娠20 - 28周前至少连续发生三次流产。有多种病因与免疫、解剖、内分泌、遗传、感染、染色体异常及环境因素相关，这些因素共同导致了这种情况。本研究的目的是利用蛋白质组学确定人类血液中与复发性流产相关的因素。由于难以获取组织或卵泡液，我们使用正常人和复发性流产患者的血液样本进行了比较蛋白质组学研究。使用了三份复发性流产血液样本和一份来自三名正常女性的混合血液样本。我们进行了二维电泳（2-DE），并对选定的斑点用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF/MS）进行分析。在三份复发性流产血液样本中，二维电泳分析分别显示有549、563和533个斑点差异表达。通过对照组与复发性流产组的比较分析，有21个斑点显示差异表达。其中，5种蛋白质通过蛋白质免疫印迹分析得到证实。这些蛋白质之一，ITI-H4（α-胰蛋白酶抑制剂重链4），在分子量120 kDa时表达较弱，但在复发性流产患者中经修饰后的分子量36 kDa时高表达。这些发现表明，ITI-H4的表达可能用作生物标志物，这有助于开发新的诊断和治疗工具。
