Fig. 1

Potential mechanisms of steroid hormones action on the uNK cells. Through classical steroid receptors (e.g. GR, ERRβ), non-classical pathways or intermediary cells in the surrounding, progesterone and estrogen probably affect gene transcription, secondary messenger and membrane potential to regulate the activities of uNK cells. Among them, non-classical pathways referring to ion channels (e.g. SLC) and membrane-bound receptors are mainly contributed to rapid actions of the hormones. For progesterone, PGMRC1 and mPR are two potential candidates of membrane-bound receptors on the uNK cells and function as G protein-coupled receptors to activate or inhibit downstream G protein. For estrogen, its membrane-bound receptors may be coupled to mGluR2 and initiate intracellular signaling pathway of mGluR2 to regulate uNK cells activities. Otherwise, both progesterone and estrogen are likely to reduce IL-18 level in endometrial stromal cell (SC) and dendritical cells (DC) to inhibit cytotoxicity of uNK cells and improve pregnant outcomes