The study found that women who have had repeated miscarriages show lower levels of the hormone kisspeptin in the cells that form the placenta, and this drop is linked to higher numbers of certain immune cells (NK cells) in the uterus. The kisspeptin receptor didn’t change, and more NK cells were seen when blood NK cells were high, which correlated with the lower kisspeptin levels.

Kisspeptin and its receptor GPR54 play a major role in trophoblast invasion. The expression of kisspeptin and GPR54 in trophoblast and decidua and their relationship with decidual and peripheral blood natural killer (NK) cells are investigated in women with RPL. Trophoblast and decidual tissues were collected from 38 RPL women who miscarried a genetically normal fetus and 14 women who had elective abortion. Kisspeptin, GPR54, and decidual NK cells were investigated with immunohistochemistry, and peripheral blood NK cells were analyzed by flow cytometry. Kisspeptin expression in syncytiotrophoblast was significantly decreased in RPL women with normal (<15%) peripheral blood NK cells (npNK) (P=0.021) and high (≥15%) peripheral blood NK cells (hpNK) (P=0.024) as compared to controls. Kisspeptin expression in cytotrophoblast was significantly decreased hpNK group (P=0.009) as compared to controls. GPR54 expressions were not different among study groups and controls. The number of CD56(+) decidual NK cells are significantly higher in hpNK group as compared to npNK group (P=0.041) and showed a correlation with kisspeptin expression in syncytiotrophoblasts (r=0.738, P<0.001). Decreased kisspeptin expression in trophoblasts is associated with RPL and kisspeptin may engage the regulation of decidual NK cell infiltration.