Floating Hospital for Children at Tufts Medical Center, Department of Pediatrics, Division of Newborn Medicine 800 Washington Street, Box 44 Boston, MA 02111.
Proteomics Clin Appl. 2009 Dec;3(12):1389-96. doi: 10.1002/prca.200900109.
Although the measurement of fetal proteins in maternal serum is part of standard prenatal screening for aneuploidy and neural tube defects, attempts to better understand the extent of feto-maternal protein trafficking and its clinical and biological significance have been hindered by the presence of abundant maternal proteins. The objective of this study was to circumvent maternal protein interference by using a computational predictive approach for the development of a noninvasive, comprehensive, protein network analysis of the developing fetus in maternal whole blood. From a set of 157 previously identified fetal gene transcripts, 46 were classified into known protein networks, and 222 downstream proteins were predicted. Statistically significantly over-represented pathways were diverse and included T-cell biology, neurodevelopment and cancer biology. Western blot analyses validated the computational predictive model and confirmed the presence of specific downstream fetal proteins in the whole blood of pregnant women and their newborns, with absence or reduced detection of the protein in the maternal postpartum samples. This work demonstrates that extensive feto-maternal protein trafficking occurs during pregnancy, and can be predicted and verified to develop novel noninvasive biomarkers. This study raises important questions regarding the biological effects of fetal proteins on the pregnant woman.
尽管胎儿蛋白在母体血清中的测量是用于检测非整倍体和神经管缺陷的标准产前筛查的一部分，但由于存在丰富的母体蛋白，尝试更好地理解胎母蛋白转运的程度及其临床和生物学意义一直受到阻碍。本研究的目的是通过使用计算预测方法来规避母体蛋白的干扰，从而对母体全血中的胎儿进行非侵入性、全面的蛋白质网络分析。从之前确定的 157 个胎儿基因转录本中，将 46 个分类为已知的蛋白质网络，并预测了 222 个下游蛋白质。统计上显著过表达的途径多种多样，包括 T 细胞生物学、神经发育和癌症生物学。Western blot 分析验证了计算预测模型，并证实了特定的下游胎儿蛋白存在于孕妇及其新生儿的全血中，而在产后的母体样本中则检测不到或减少了该蛋白。这项工作表明，在怀孕期间发生了广泛的胎母蛋白转运，并且可以进行预测和验证，以开发新的非侵入性生物标志物。本研究提出了关于胎儿蛋白对孕妇的生物学影响的重要问题。
