Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural killer cells in pregnant women with a history of recurrent pregnancy loss.

Abstract

Natural cytotoxicity receptors (NCR) are unique markers that regulate natural killer (NK) cell cytotoxicity and cytokine production. In this study, we investigated the expression of NCR (NKp46, NKp44, and NKp30) and cytokine production in NK cells derived from the uterine endometrium of women with recurrent pregnancy loss (RPL). We also investigated the expression of NCR in peripheral blood NK cells in pregnant women with and without a history of RPL. The expression of NCR (NKp46, NKp44, and NKp30) in NK cells (CD56dim and CD56bright ) in the uterine endometrium was analyzed using 3-color flow cytometry. Cytokine (tumor necrosis factor-α and interferon-γ) production was also analyzed. NK cells from the mid-secretory endometrium of 28 women with RPL, 34 women with implantation failure, and 74 controls were collected and mechanically dispersed using a tissue grinder. The expression of NCR in peripheral blood NK cells from pregnant women with (n = 17) and without (n = 91) a history of RPL was analyzed. The percentages of NKp46+ NK cells were significantly lower in both women with RPL and pregnant women with a history of RPL. The percentages of tumor necrosis factor-α- and/or interferon-γ-producing uterine endometrial NK cells were significantly lower in women with RPL compared with controls. The changes in NCR expression and cytokine production, especially decreased NKp46 expression in endometrial NK cells, suggests the presence of abnormal NK cell regulation in women with reproductive failures.