Hannan Natalie J, Jones Rebecca L, White Christine A, Salamonsen Lois A
Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia.
Biol Reprod. 2006 May;74(5):896-904. doi: 10.1095/biolreprod.105.045518. Epub 2006 Feb 1.
Human embryo implantation is a complex process involving blastocyst attachment to the endometrial epithelium and subsequent trophoblast invasion of the decidua. Chemokines, critical regulators of leukocyte migration, are abundant in endometrial epithelial and decidual cells at this time. We hypothesized that endometrial chemokines stimulate trophoblast invasion. Chemokine receptors CX3CR1 and CCR1 were immunolocalized in human first-trimester implantation sites, specifically to endovascular extravillous trophoblasts, but not to the invading interstitial EVTs (iEVTs), with weak staining also on syncytium. CCR3 was localized to invading iEVTs and to microvilli on the syncytial surface. Expression of CX3CL1 (fractalkine), CCL7 (MCP-3), and their receptors (CX3CR1, CCR1, CCR2, CCR3, and CCR5) mRNA was examined in cellular components of the maternal-embryonic interface by RT-PCR. Both chemokines were abundant in entire endometrium and placenta, endometrial cells (primary cultures and HES, a human endometrial epithelial cell line) and trophoblast cell lines (JEG-3, ACIM-88, and ACIM-32). Chemokine receptor mRNA was expressed by placenta and trophoblast cell lines: CCR1 by all trophoblast cell types, whereas CCR2, CCR3, and CX3CR1 were more variable. CX3CR1, CCR1, CCR2, and CCR5 were also expressed by endometrial cells. Migration assays used the trophoblast cell line most closely resembling extravillous cytotrophoblast (AC1M-88). Trophoblast migration occurred in response to CX3CL1, CCL14, and CCL4, but not CCL7. Endometrial cell-conditioned media also stimulated trophoblast migration; this was attenuated by neutralizing antibodies to CX3CL1 and CCL4. Thus, chemokines are expressed by maternal and embryonic cells during implantation, whereas corresponding receptors are on trophoblast cells. Promotion of trophoblast migration by chemokines and endometrial cell conditioned medium indicates an important involvement of chemokines in maternal-fetal communication.
人类胚胎着床是一个复杂的过程，涉及囊胚附着于子宫内膜上皮以及随后滋养层对蜕膜的侵袭。趋化因子是白细胞迁移的关键调节因子，此时在子宫内膜上皮细胞和蜕膜细胞中大量存在。我们推测子宫内膜趋化因子会刺激滋养层的侵袭。趋化因子受体CX3CR1和CCR1在人类孕早期着床部位进行免疫定位，特别定位于血管内绒毛外滋养层细胞，但不包括侵袭性间质绒毛外滋养层细胞（iEVT），合体滋养层也有弱阳性染色。CCR3定位于侵袭性iEVT以及合体滋养层表面的微绒毛。通过逆转录聚合酶链反应（RT-PCR）检测了母胎界面细胞成分中CX3CL1（fractalkine）、CCL7（MCP-3）及其受体（CX3CR1、CCR1、CCR2、CCR3和CCR5）mRNA的表达。这两种趋化因子在整个子宫内膜和胎盘中、子宫内膜细胞（原代培养细胞和HES，一种人子宫内膜上皮细胞系）以及滋养层细胞系（JEG-3、ACIM-88和ACIM-32）中都大量存在。趋化因子受体mRNA在胎盘和滋养层细胞系中表达：所有类型的滋养层细胞都表达CCR1，而CCR2、CCR3和CX3CR1的表达则更具变异性。CX3CR1、CCR1、CCR2和CCR5也在子宫内膜细胞中表达。迁移试验使用了与绒毛外细胞滋养层最相似的滋养层细胞系（AC1M-88）。滋养层细胞的迁移对CX3CL1、CCL14和CCL4有反应，但对CCL7无反应。子宫内膜细胞条件培养基也刺激滋养层细胞迁移；针对CX3CL1和CCL4的中和抗体可减弱这种刺激作用。因此，在着床过程中，母细胞和胚胎细胞都表达趋化因子，而相应的受体则存在于滋养层细胞上。趋化因子和子宫内膜细胞条件培养基对滋养层细胞迁移的促进作用表明趋化因子在母胎通讯中具有重要作用。
