The regulation of ovary and conceptus on the uterine natural killer cells during early pregnancy

Han Gong, Yilu Chen, Jingjie Xu, Xingxing Xie, Dainan Yu, Bei Yang, Haibin Kuang

Uterine natural killer (uNK) cells are short-lived, terminally differentiated and the most abundant lymphocytes in the uterus which play a crucial role in the spiral arteriole modification and establishment of successful pregnancy. Dysregulation of uNK cells has been linked to gestational implications such as recurrent pregnancy loss, preeclampsia and fetal growth retardation. There is evidence showing that progesterone and estrogen can regulate the recruitment, proliferation, differentiation and function of uNK cells via direct action on intracellular nuclear receptors or through intermediary cells in the uterus during early pregnancy. As the deepening of related research in this field, the role of conceptus in such regulation has received extensive attention, it utilizes endocrine signaling (hCG), juxtacrine signaling (HLA-C, HLA-E, HLA-G) and paracrine signaling (cytokines) to facilitate the activities of uNK cells. In addition, under the influence of ovarian hormones, conceptus can increase expression of PIBF and HLA-G molecules to reduce cytotoxicity of uNK cells and promote angiogenesis. In this review, we aim to concentrate on the novel findings of ovarian hormones in the regulation of uNK cells, emphasize the regulatory role of conceptus on uNK cells and highlight the proposed issues for future research in the field.