Caballero-Campo Pedro, Domínguez Francisco, Coloma Julio, Meseguer Marcos, Remohí José, Pellicer Antonio, Simón Carlos
Fundación Instituto Valenciano de Infertilidad para el Estudio de la Reproducción Humana (FIVIER), Universidad de Valencia, España.
Mol Hum Reprod. 2002 Apr;8(4):375-84. doi: 10.1093/molehr/8.4.375.
Chemokines are a family of small polypeptides which specialize in the attraction of leukocytes. The presence of specific leukocyte subsets at the implantation site is an important element of the complex, and not completely understood, process of embryonic implantation. This report includes the investigation of the in-vivo immunolocalization and hormonal regulation of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and RANTES (regulated upon activation normal T-cell expressed and secreted) in the human endometrium during hormone replacement therapy cycles for oocyte recipients in an IVF programme. In addition, we have analysed the embryonic regulation of these endometrial epithelial chemokines (IL-8 and MCP-1) using an in-vitro model for the apposition phase of human implantation by co-culturing single human embryos until the blastocyst stage with human endometrial epithelial cells (EEC). IL-8 and MCP-1 were immunolocalized in the human endometrium to the glandular and lumenal epithelium as well as to the endothelial cells. RANTES was mainly localized to the stromal compartment and endothelial cells. The immunoreactive levels of endometrial IL-8 and MCP-1 were up-regulated by the administration of progesterone during the receptive phase of the cycle. Furthermore, it was demonstrated that, in vitro, the human blastocyst does not produce measurable amounts of IL-8, MCP-1 or RANTES; however, it does up-regulate EEC IL-8 mRNA expression (P < 0.05) and protein production (P < 0.05), but not IL-8 secretion. The human embryo did not regulate EEC MCP-1 expression. These results provide evidence of hormonal and embryonic regulation of specific endometrial chemokines, suggesting two different but related mechanisms to induce the production of chemokines by the EEC, thus contributing to the attraction of specific leukocyte populations during the peri-implantation phase.
趋化因子是一类专门负责吸引白细胞的小多肽家族。特定白细胞亚群在着床部位的存在是复杂且尚未完全了解的胚胎着床过程的一个重要因素。本报告包括在体外受精（IVF）项目中，对接受激素替代治疗周期的卵母细胞受体的人子宫内膜中白细胞介素（IL）-8、单核细胞趋化蛋白（MCP）-1和调节激活正常T细胞表达和分泌因子（RANTES）的体内免疫定位和激素调节的研究。此外，我们使用人胚胎着床附着期的体外模型，将单个人类胚胎与人子宫内膜上皮细胞（EEC）共培养至囊胚期，分析了这些子宫内膜上皮趋化因子（IL-8和MCP-1）的胚胎调节作用。IL-8和MCP-1在人子宫内膜中免疫定位到腺上皮和腔上皮以及内皮细胞。RANTES主要定位于间质区和内皮细胞。在周期的接受期给予孕酮可上调子宫内膜IL-8和MCP-1的免疫反应水平。此外，还证明在体外，人类囊胚不会产生可测量量的IL-8、MCP-1或RANTES；然而，它确实上调了EEC的IL-8 mRNA表达（P < 0.05）和蛋白质产生（P < 0.05），但不影响IL-8的分泌。人类胚胎未调节EEC的MCP-1表达。这些结果提供了特定子宫内膜趋化因子的激素和胚胎调节的证据，提示了两种不同但相关的机制来诱导EEC产生趋化因子，从而有助于在着床周围期吸引特定的白细胞群体。
