Human Reproduction, Vol. 17, No. 4, 1072-1080,
April 2002
© 2002 European Society of Human Reproduction and Embryology
Altered phenotype of HLA-G expressing trophoblast and decidual natural killer cells in pathological pregnancies
1 Department of Blood Transfusion and Transplantation Immunology, 2 Department of Obstetrics and Gynaecology and 3 Department of Pathology, University Medical Centre Nijmegen, 6500 HB, Nijmegen and 4 Department of Obstetrics and Gynaecology, Academic Medical Centre Amsterdam, 1105 AZ Amsterdam, The Netherlands
BACKGROUND: The interaction between decidual natural killer (NK) cells and alloantigens expressed on fetal trophoblast cells are thought to be essential for successful implantation and placentation. Consequently, a disturbed interaction during the first trimester of pregnancy might well lead to a subsequent pregnancy failure. METHODS: We investigated the expression of HLA-G and NK cell markers in tissue sections from recurrent miscarriage (n = 9) and ectopic tubal pregnancies (n = 5), and two hysterectomy specimens of healthy pregnancy as well as decidual biopsies (n = 9) were used as controls. RESULTS: We show in normal pregnancy not only a decrease, but also a morphological change in CD56+ NK cells upon interaction with HLA-G-expressing trophoblasts. The cells appear to be transitioning from a blast-like (activation) state into a state of apoptosis. The number of CD16+ NK cells was low. In contrast, in recurrent miscarriage tissue a sustained NK cell marker expression of both CD56 and CD16 was paralleled by a decreased expression of HLA-G. No morphological changes from the blast-like stage were apparent. Finally, in ectopic pregnancies HLA-G expression in the absence of decidual NK cells was associated with a disturbed trophoblast differentiation. CONCLUSIONS: In pathological pregnancies we show an in-situ altered phenotype of trophoblast and NK cells.
Key words: ectopic pregnancy/HLA-G/human/recurrent miscarriage/trophoblast
5 To whom correspondence should be addressed at: Department of Blood Transfusion and Transplantation Immunology, Geert Grooteplein 10, PO Box 9101, 6500 HB, Nijmegen 603/ABTI, The Netherlands. E-mail: i.joosten{at}utdts.azn.nl
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