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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 12 6155-6167
Copyright © 2004 by The Endocrine Society

Identification of Chemokines Important for Leukocyte Recruitment to the Human Endometrium at the Times of Embryo Implantation and Menstruation

Rebecca L. Jones, Natalie J. Hannan, Tu’uhevaha J. Kaitu’u, Jin Zhang and Lois A. Salamonsen

Prince Henry’s Institute of Medical Research (R.L.J., N.J.H., T.J.K., J.Z., L.A.S.), Clayton, Victoria 3168, Australia; and Department of Immunology (N.J.H.), Monash University, Prahran, Victoria 3181, Australia

Address all correspondence and requests for reprints to: Rebecca Jones, Prince Henry’s Institute of Medical Research, Clayton, Victoria, Australia 3186. E-mail: rebecca.jones{at}phimr.monash.edu.au.

Human endometrium possesses a unique immunological environment enabling implantation of the semiallogeneic embryo. Large populations of macrophages and uterine-specific natural killer cells infiltrate the implantation site, believed to be important modulators of trophoblast invasion and decidualization. In the absence of pregnancy, there is a dramatic influx of neutrophils, eosinophils, and macrophages, likely to be critical for focal inflammatory endometrial destruction. However, little is known regarding selective recruitment of leukocyte subtypes. We employed a gene array approach to analyze the expression of 21 chemokines in endometrium. Real-time RT-PCR and immunohistochemistry was conducted to verify expression patterns and determine cellular source. Nine chemokines were highly abundant in human endometrium: monocyte chemotactic protein-3, eotaxin, fractalkine, macrophage inflammatory protein-1ß, 6Ckine, IL-8, hemofiltrate CC chemokine-1 and -4, and macrophage-derived chemokine. Chemokine mRNA was generally up-regulated during endometrial receptivity and early pregnancy, particularly of macrophage and natural killer chemoattractants. Chemokine protein was predominantly localized to epithelial glands, whereas differentiated stromal cells were a major source of chemokines after decidualization. This is the first study to use an unbiased approach to screen for endometrial chemokines, and we report the selective regulation of chemokines, corresponding to the recruitment of distinct leukocyte subpopulations required for pregnancy and menstruation.




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