Genetic link to risky pregnancy

October 11, 2004

When a particular combination of proteins is expressed by a mother and her developing fetus, the risk of developing preeclampsia increases, according to a study by Hiby and colleagues in the Oct 18 issue of The Journal of Experimental Medicine.

Preeclampsia, a serious complication of pregnancy, develops when the cells responsible for routing blood and nutrients to the placenta are unable to do their job. The result is decreased blood flow to the fetus, a situation that threatens both mother and developing child. The fetal cells charged with this important task, called trophoblast cells, must communicate with maternal immune cells known as natural killer (NK) cells. During these interactions, the trophoblast sends signals to the NK cells, which can then assist them in the 'invasion' and remodeling of the blood vessels required to sustain the fetus.

The signals delivered to the NK cells can be stimulatory or inhibitory, depending on the types of proteins expressed by the NK cells and trophoblasts. To ensure that the NK cells get the right message, a balance between these opposing signals must be achieved. In this study, Hiby et al analyzed the genes that encode these proteins in groups of women with and without a history of preeclampsia. The expression of a particular type of protein on the trophoblast in combination with its receptor on NK cells was more common in women with a history of preeclampsia. This protein combination is expected to deliver a signal that suppresses the NK cells, robbing them of the ability to help stimulate vessel remodeling.

This is a seemingly unusual role for NK cells, whose traditional job in the circulation is to recognize and destroy infected cells and tumor cells. "We don't really know what the NK cells are doing", the authors point out. These NK cells "are present only in the uterus during trophoblast invasion, and are presumably acting by secreting [immune mediators called] cytokines." In the immune system, cytokines recruit and activate other cell types, so perhaps a similar phenomenon is occurring during pregnancy.
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Journal of Experimental Medicine

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