Decidual stromal cell response to paracrine signals from the trophoblast: Amplification of immune and angiogenic modulators
Decidual stromal cell response to paracrine signals from the trophoblast: Amplification of immune and angiogenic modulators
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DOI：
10.1095/biolreprod.106.054791
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发表时间：
2007-01-01
影响因子：
3.6
通讯作者：
Giudice, L. C.
中科院分区：
文献类型：
--
作者：
Hess, A. P.;Hamilton, A. E.;Giudice, L. C.
在植入侵入期，滋养细胞和母体蜕质细胞分泌调节滋养细胞分化和向母体子宫内膜迁移的产物。卵泡外滋养细胞和母体蜕膜之间的旁分泌相互作用对胚胎着床的成功至关重要，包括建立胎盘血管，将胎盘固定在子宫壁上，以及促进胎儿异体的免疫接受。据我们所知，滋养细胞和蜕膜之间的全局串扰迄今尚未阐明，本研究使用功能基因组学方法来研究这些旁分泌相互作用。用黄体酮对人子宫内膜基质细胞进行脱体细胞处理，然后用人滋养细胞（TCM）的条件培养基处理，或者用非脱体细胞基质细胞的对照条件培养基（CCM）处理，分别处理0、3和12小时。分离总RNA，处理后用于包含54 600个基因的全基因组高密度寡核苷酸阵列分析。我们发现，与CCM相比，中药与基质细胞共孵育12 h后，1374个基因显著上调，3443个基因显著下调。上调最多的基因包括趋化因子CXCL1 （GRO1）和IL8、CXCR4，以及其他参与免疫反应的基因（CCL8 [SCYA8]、五胞素3 （PTX3）、IL6和干扰素调控及相关基因），以及TNFAIP6（肿瘤坏死因子α诱导蛋白6）和金属蛋白酶（MMP1、MMP10和MMP14）。下调的基因包括生长因子，如lGF1、FGF1、TGFB1和血管生成素-1，以及参与Writ信号的基因（WNT4和FZD）。Real-time RT-PCR和elisa以及人胎盘床标本的免疫组织化学分析证实了上调和下调组的代表性基因的这些数据。这些数据表明，在滋养细胞分泌产物的反应中，去个体化子宫内膜基质细胞显著诱导了促炎细胞因子和趋化因子，以及血管生成/静态因子。这些数据表明，滋养细胞通过改变蜕膜的局部免疫环境来促进着床过程，确保细胞因子/趋化因子环境的富集，同时限制基质细胞在着床侵袭期的有丝分裂活性。
During the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important for successful embryonic implantation, including establishing the placental vasculature, anchoring the placenta to the uterine wall, and promoting the immunoacceptance of the fetal allograph. To our knowledge, global crosstalk between the trophoblast and the decidua has not been elucidated to date, and the present study used a functional genomics approach to investigate these paracrine interactions. Human endometrial stromal cells were decidualized with progesterone and further treated with conditioned media from human trophoblasts (TCM) or, as a control, with control conditioned media (CCM) from nondecidualized stromal cells for 0, 3, and 12 h. Total RNA was isolated and processed for analysis on whole-genome, high-density oligonucleotide arrays containing 54 600 genes. We found that 1374 genes were significantly upregulated and that 3443 genes were significantly downregulated after 12 h of coincubation of stromal cells with TCM, compared to CCM. Among the most upregulated genes were the chemokines CXCL1 (GRO1) and IL8, CXCR4, and other genes involved in the immune response (CCL8 [SCYA8], pentraxin 3 (PTX3), IL6, and interferon-regulated and -related genes) as well as TNFAIP6 (tumor necrosis factor alpha-induced protein 6) and metalloproteinases (MMP1, MMP10, and MMP14). Among the downregulated genes were growth factors, e.g., lGF1, FGF1, TGFB1, and angiopoietin-1, and genes involved in Writ signaling (WNT4 and FZD). Real-time RT-PCR and ELISAs, as well as immunohistochemical analysis of human placental bed specimens, confirmed these data for representative genes of both up- and downregulated groups. The data demonstrate a significant induction of proinflammatory cytokines and chemokines, as well as angiogenic/static factors in decidualized endometrial stromal cells in response to trophoblast-secreted products. The data suggest that the trophoblast acts to alter the local immune environment of the decidua to facilitate the process of implantation and ensure an enriched cytokine/chemokine environment while limiting the mitotic activity of the stromal cells during the invasive phase of implantation.