Altered phenotype of HLA-G expressing trophoblast and decidual natural killer cells in pathological pregnancies

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.