Yale Women and Children's Center for Blood Disorders, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
Am J Obstet Gynecol. 2010 May;202(5):459.e1-8. doi: 10.1016/j.ajog.2010.03.024.
Preimplantation factor (PIF) is a novel, 15 amino acid peptide, secreted by viable embryos. This study aims to elucidate PIF's effects in human endometrial stromal cells (HESC) decidualized by estrogen and progestin, which mimics the preimplantation milieu, and in first-trimester decidua cultures (FTDC).
HESC or FTDC were incubated with 100 nmol/L synthetic PIF or vehicle control. Global gene expression was analyzed using microarray and pathway analysis. Proteins were analyzed using quantitative mass spectrometry, and PIF binding by protein array.
Gene and proteomic analysis demonstrate that PIF affects immune, adhesion, and apoptotic pathways. Significant up-regulation in HESC (fold change) include: nuclear factor-k-beta activation via interleukin-1 receptor-associated kinase binding protein 1 (53); Toll-like receptor 5 (9); FK506 binding protein 15, 133kDa protein (2.3); and Down syndrome cell adhesion molecule like 1 (16). B-cell lymphoma protein 2 was down-regulated in HESC (21.1) and FTDC (27.1). Protein array demonstrates PIF interaction with intracellular targets insulin-degrading enzyme and beta-K+ channels.
PIF displays essential multitargeted effects, of regulating immunity, promoting embryo-decidual adhesion, and regulating adaptive apoptotic processes.
植入前因子（PIF）是一种新型的 15 个氨基酸肽，由有活力的胚胎分泌。本研究旨在阐明 PIF 在雌激素和孕激素诱导的人子宫内膜基质细胞（HESC）蜕膜化，模拟植入前环境，以及在早孕期蜕膜培养（FTDC）中的作用。
用 100nmol/L 合成 PIF 或载体对照孵育 HESC 或 FTDC。采用微阵列和通路分析对全基因组表达进行分析。采用定量质谱分析蛋白质，采用蛋白质阵列分析 PIF 结合。
基因和蛋白质组学分析表明，PIF 影响免疫、黏附和细胞凋亡途径。HESC 中显著上调的基因（倍数变化）包括：白细胞介素 1 受体相关激酶结合蛋白 1 核因子-k-β的激活（53）；Toll 样受体 5（9）；FK506 结合蛋白 15，133kDa 蛋白（2.3）；唐氏综合征细胞黏附分子样 1（16）。B 细胞淋巴瘤蛋白 2 在 HESC（21.1）和 FTDC（27.1）中下调。蛋白质阵列表明 PIF 与细胞内靶标胰岛素降解酶和β-K+通道相互作用。
PIF 显示了调节免疫、促进胚胎-蜕膜黏附、调节适应性细胞凋亡过程的重要多靶向作用。
