title: Hormonal and embryonic regulation of chemokines IL-8, MCP-1 and RANTES in the human endometrium during the window of implantation.
abstract: 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.
authors.affiliation: Fundación Instituto Valenciano de Infertilidad para el Estudio de la Reproducción Humana (FIVIER), Universidad de Valencia, España.
authors.forename: Pedro
authors.initials: P
authors.lastname: Caballero-Campo
authors.forename: Francisco
authors.initials: F
authors.lastname: Domínguez
authors.forename: Julio
authors.initials: J
authors.lastname: Coloma
authors.forename: Marcos
authors.initials: M
authors.lastname: Meseguer
authors.forename: José
authors.initials: J
authors.lastname: Remohí
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
mesh_terms: D001755:Blastocyst / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; D016209:Interleukin-8