Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome
Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome
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DOI：
10.1093/molehr/gal048
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发表时间：
2006-07-01
影响因子：
4
通讯作者：
Brosens, Jan J.
中科院分区：
文献类型：
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作者：
Francis, Julia;Rai, Raj;Brosens, Jan J.
抗磷脂综合征（APS）以循环抗磷脂（aPL）抗体为特征，是早期妊娠失败和胎盘功能不全的主要原因。在这项研究中，我们研究了受孕前子宫内膜分化受损是否会导致 APS 妊娠并发症的高发生率。从一组患有复发性流产（RPL）的妇女中获得定时分泌性子宫内膜活检。实时定量 (RTQ)-PCR 用于测定编码蜕膜标记物、促炎细胞因子和补体调节蛋白的转录物的表达水平。与 aPL(-) 组 (n = 58) 相比，从 aPL(+) 患者 (n = 24) 获得的样本中，催乳素 (PRL)、组织因子 (TF) 和信号转导子和转录激活子 5 (Stat5) 等蜕膜标志物的表达显着较低，但胰岛素样生长因子结合蛋白 1 (IGFBP-1) 则不然 (P < 0.05)。编码干扰素γ（IFNγ）、肿瘤坏死因子α（TNFα）或Stat1的转录物丰度在两组之间没有显着差异（P>=0.05）。然而，对编码补体调节蛋白的转录本的分析显示，aPL(+)患者的衰变加速因子（DAF/CD55）水平显着降低（P = 0.005），这与免疫组织化学所证明的蛋白质水平相似。总之，RPL 患者具有不同的子宫内膜基因表达谱，具体取决于循环 aPL 抗体的存在或不存在。在 APS 中，受孕前子宫内膜分化受损和 DAF/CD55 表达较低可能会影响着床并易导致补体介导的妊娠失败。
Antiphospholipid syndrome (APS), characterized by circulating antiphospholipid (aPL) antibodies, is a major cause of early pregnancy failure and placental insufficiency. In this study, we examined whether impaired endometrial differentiation before conception contributes to the high incidence of pregnancy complications in APS. Timed secretory endometrial biopsies were obtained from a cohort of women with recurrent pregnancy loss (RPL). Real-time quantitative (RTQ)-PCR was used to determine the expression levels of transcripts that encode for decidual markers, proinflammatory cytokines and complement regulatory proteins. Expression of decidual markers such as prolactin (PRL), tissue factor (TF) and signal transducer and activator of transcription 5 (Stat5), but not insulin-like growth factor-binding protein 1 (IGFBP-1), was significantly lower in samples obtained from aPL(+) patients (n = 24) when compared with aPL(-) group (n = 58) (P < 0.05). The abundance of transcripts encoding for interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha) or Stat1 did not differ significantly between both groups (P >= 0.05). However, analysis of transcripts that encode for complement regulatory proteins showed a marked decrease in decay-accelerating factor (DAF/CD55) levels in aPL(+) patients (P = 0.005), which was mimicked at protein level as demonstrated by immunohistochemistry. In summary, patients with RPL have distinct endometrial gene expression profiles depending on the presence or absence of circulating aPL antibodies. In APS, impaired endometrial differentiation and lower DAF/CD55 expression before conception may compromise implantation and predispose to complement-mediated pregnancy failure.