Uterine and Circulating Natural Killer Cells and Their Roles in Women with Recurrent Pregnancy Loss, Implantation Failure and Preeclampsia

The regulation of uterine and circulating peripheral blood natural killer (NK) cells has been associated with reproductive conditions including recurrent pregnancy loss (RPL), implantation failure and preeclampsia. Natural cytotoxicity receptors (NCRs) are unique markers that regulate NK cell cytotoxicity and cytokine production. The role of NCRs in reproductive events has not yet been fully characterized. There is an NK1 (Type 1) shift in peripheral blood NK cells in non-pregnant women prone to RPL and implantation failure. The different profile of NCR expression in endometrial or aborted decidual NK cells suggests the presence of abnormal regulation of NK cells in women with reproductive failure. Women with a history of RPL and preeclampsia carry immunological abnormalities of NCRs on peripheral blood NK cells during pregnancy. Evaluation of NKp46 on peripheral blood NK cells may be applicable for the prediction of preeclampsia. The lower expression of NKp46(+) NK cells in women with preeclampsia may account for the higher production of NK1 cytokines - known as the NK1 shift - in pregnant women with preeclampsia. In this review, the expression of NCRs in peripheral blood NK cells and endometrial or decidual NK cells is discussed in relation to reproductive failure.