205. Fractalkine, HCC-1 and MIP-1β promote human trophoblast migration
N. J. Hannan A B , R. L. Jones A and L. A. Salamonsen AA Prince Henry’s Institute of Medical Research, Clayton, VIC, Australia
B Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
Reproduction, Fertility and Development 17(9) 78-78 https://doi.org/10.1071/SRB05Abs205
Submitted: 26 July 2005 Accepted: 26 July 2005 Published: 5 September 2005
Abstract
Human embryo implantation is a complex process requiring the attachment of an activated blastocyst to receptive endometrial epithelium and subsequent trophoblast invasion throughout the first trimester of pregnancy. Chemokines, including fractalkine (FKN), MCP-3, HCC-1 and MIP-1β, are produced by human endometrial epithelial and decidual cells with maximal production around the time of implantation/early pregnancy.1,2 Chemokine and receptor expression was characterized in cell types at the human maternal–trophoblast interface. Highly abundant expression of chemokine receptors CX3CR1 and CCR1 was observed in first trimester placenta and in trophoblast cells.3 We hypothesized that CX3CR1 and CCR1 ligands (FKN, MCP-3, HCC-1 and MIP-1β) produced by endometrial epithelial and decidualised stromal cells at the time of implantation promote migration of human trophoblast. We aimed to localize specific chemokine receptors in human first trimester tissue, and to determine whether trophoblast migration could be stimulated by the endometrium and by chemokines. Cellular localisation of specific receptors was assessed by immunohistochemistry in human first trimester implantation sites. Using an in vitro assay, trophoblast migration was assessed in response to human endometrial epithelial (HEEC) and decidualised stromal cells (DESC) (serum-free) conditioned medium and to recombinant human FKN, MCP-3, HCC-1 and MIP-1β. CX3CR1 and CCR1 protein was localised to the vascular extravillous trophoblast (EVTs), but not to the invading interstitial EVTs, with weak staining on the syncytium. Significant migration of cells occurred in response to conditioned media from HEEC and DESC. FKN, MIP-1β and HCC-1, but not MCP-3 also promoted significant trophoblast migration. Neutralizing antibodies for FKN and MIP-1β but not MCP-3 significantly reduced migration to conditioned media, indicating that at least these two chemokines contributed to the effects. These data support a role for endometrial derived chemokines in promoting human trophoblast migration.
(1) Jones et al. (2004). JCEM 89(12), 6155–6167.
(2) Hannan et al. (2004). Reprod. Fert. Devel. 16(Suppl.), A225, p. 78.
(3) Hannan et al. (2004). JCEM 89(12), 6119–6129.
