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A more recent version of this article appeared on January 1, 2009

Published online before print September 17, 2008
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0708395

Received for publication July 1, 2008.
Revised August 14, 2008.
Accepted for publication August 14, 2008.

Article

Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment

Maaike S. M. van Mourik *, Nick S. Macklon {dagger}, and Cobi J. Heijnen *@

University Medical Center Utrecht, Departments of *Psychoneuroimmunology and {dagger}Reproductive Medicine and Gynecology, Utrecht, The Netherlands

@ To whom correspondence should be addressed. E-mail: c.heijnen{at}umcutrecht.nl.


  Abstract

Successful implantation is an absolute requirement for the reproduction of species, including humans. The process by which a foreign blastocyst is accepted by the maternal endometrium is complex and requires interplay of many systems. Implantation occurs during the putative implantation window, in which the maternal endometrium is ready to accept the blastocyst, which on the other hand, also plays a specific role. It produces cytokines and chemokines and expresses adhesion molecules and certain classes of MHC molecules. We review the most important players in implantation. Concerning the cytokines, the establishment of controlled aggression is key; an excess of pro- or anti-inflammation is detrimental to pregnancy outcome. Chemokines control the orientation of the embryo. The adhesion molecules are necessary to establish the required physical interaction between mother and blastocyst. Finally, immune cells and in particular, uterine NK and regulatory T cells are pivotal in inducing tolerance to the blastocyst. The aim of this review is to discuss mechanisms at play and their relative importance to the establishment of pregnancy.

Key Words: regulatory T cells • tolerance • uterine NK cell • chemokine






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