Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Immunol Cell Biol. 2011 Feb;89(2):304-13. doi: 10.1038/icb.2010.95. Epub 2010 Aug 3.
Successful pregnancy requires coordinated maternal-fetal cross-talk to establish vascular connections that support conceptus growth. In pigs, two waves of spontaneous fetal loss occur and 30-40% of conceptuses are lost before parturition. Previous studies associated these losses with decreased angiogenic and increased inflammatory cytokines. Chemokines, a sub-category of cytokines, and decoy receptors control leukocyte trafficking, angiogenesis and development. The availability of chemokines is regulated by three non-signalling decoy receptors: chemokine decoy receptor (D6), Duffy antigen receptor for chemokines (DARC) and Chemocentryx decoy receptor (CCX CKR). We hypothesized that the expression of these receptors and their chemokine ligands regulate the porcine pregnancy success or failure. Here, we describe for the first time the transcription and translation of all three decoy receptors and several chemokine ligands in endometrium and trophoblast associated with healthy and arresting conceptuses at gestation day (gd) 20 and gd50. Among decoy receptors, transcripts for DARC were significantly reduced in endometrium, whereas that for CCX CKR were significantly increased in endometrium and trophoblast at gd50 arresting compared with healthy sites. However, western blot analysis revealed no differences in decoy receptor expression between healthy and arresting tissues. Transcripts for decoy receptor ligands CCL2, CCL3, CCL4, CCL5, CCL11, CCL19, CCL21, CXCL2 and CXCL8 were stable between healthy and arresting littermates. Quantification by SearchLight chemiluminescent protein array confirmed ligand expression at the protein level. These data indicate that decoy receptors and ligands are expressed at the porcine maternal-fetal interface and dysregulation of decoy receptor (DARC and CCX CKR) transcripts occurs at sites of fetal arrest.
成功的妊娠需要协调的母婴对话来建立支持胚胎生长的血管连接。在猪中,会发生两波自发的胎儿丢失,并且在分娩前有 30-40%的胚胎丢失。以前的研究将这些丢失与血管生成减少和炎症细胞因子增加联系起来。趋化因子是细胞因子的一个亚类,以及诱饵受体控制白细胞迁移、血管生成和发育。趋化因子的可用性受到三种非信号传递的诱饵受体的调节:趋化因子诱饵受体(D6)、趋化因子 Duffy 抗原受体(DARC)和 Chemocentryx 诱饵受体(CCX CKR)。我们假设这些受体及其趋化因子配体的表达调节了猪的妊娠成功或失败。在这里,我们首次描述了在妊娠第 20 天(gd)和第 50 天(gd50)与健康和停滞胚胎相关的子宫内膜和滋养层中所有三种诱饵受体及其几种趋化因子配体的转录和翻译。在诱饵受体中,DARC 的转录本在子宫内膜中显著减少,而在 gd50 停滞的子宫内膜和滋养层中,CCX CKR 的转录本显著增加。然而,western blot 分析显示健康和停滞组织之间的诱饵受体表达没有差异。D6、CCX CKR 及其配体的表达水平可能与胚胎生长和胎盘功能的调节有关。然而,需要进一步的研究来确定这些分子在胚胎停滞中的具体作用。