TABLE 2.
Cell sources and experimental findings in functional studies of uNK cells.
| Author | Year | Experiment/key findings | Cell source |
|---|---|---|---|
| Endometrial decidualization | |||
| Gong et al. (105) | 2014 | uNK cell conditioned medium induces gene expression associated with decidualization | 7–8 week decidual tissue |
| Zhang (106) | 2018 | Coculture of uNK cells and endometrial stromal cells resulted in decidualization | First trimester decidua |
| Spiral artery remodeling | |||
| Croy et al. (118) | 1997 | No spiral artery remodeling seen in mice without uNK cells | N/A |
| Craven et al. (117) | 1998 | Early structural changes in spiral arteries occur before extravillous trophoblast arrival | First trimester elective termination samples (mean gestational age, 9 weeks); late secretory phase endometrium from surgical pathology archives, postovulatory day 10 ± 2 |
| Guimond et al. (121) | 1998 | Features of spiral artery remodeling seen in uNK cell-deficient mice after reconstitution of uNK cells through bone marrow transplants | n/a |
| Eriksson et al. (33) | 2004 | Secretomics of uNK cells | Hysterectomy specimens (included women on hormone therapy and postmenopausally, 46 ± 11 years)—created uNK clones |
| Lash et al. (61) | 2006 | uNK cells secrete angiogenic factors; higher levels secreted by uNK cells isolated from 8–10-week decidua vs. 12–14-week decidua | 8–10 week decidua, 12–14 week decidua |
| Hanna et al. (111) | 2006 | uNK cells release angiogenic factors that support vascularization in vivo | First trimester decidua |
| Smith et al. (115) | 2009 | uNK cells infiltrate vascular smooth muscle layers and secrete MMPs known to participate in artery remodeling | 8–12-week decidua |
| Robson et al. (62) | 2012 | Supernatant from uNK cells isolated from 8–10-week decidua induces disruption of vascular smooth muscle cells and breakdown of ECM components; 12–14-week uNK cells do not have this effect | First trimester decidua |
| Fraser et al. (92) | 2012 | uNK cells from first trimester pregnancies with elevated uterine artery resistance indices do not induce EC apoptosis, while those from pregnancies with normal-resistance indices do | 9–14-week decidua |
| Trophoblast invasion | |||
| Hanna et al. (111) | 2006 | uNK cells release chemoattractants that promote EVT invasion in vitro and in vivo | First trimester decidua |
| Hu (114) | 2006 | uNK cells inhibit EVT invasion through secretion of interferon gamma | 6–12-week decidua |
| Lash et al. (107) | 2010 | 12–14-week uNK cell supernatant promotes EVT invasion; 8–10-week uNK cells do not have this effect | 8–10-week decidua, 12–14-week decidua |
| De Oliveira et al. (108) | 2010 | Promotion of EVT invasion by uNK cells is partially mediated by IL-8 | 8–10-week decidua, 12–14-week decidua |
| Fraser et al. (92) | 2012 | Treatment of EVTs with uNK cell conditioned medium isolated from first trimester pregnancies with elevated uterine artery resistance indices leads to lower mobility than from pregnancies with normal artery resistance | 9–14-week decidua |
| Xiong et al. (112) | 2013 | uNK cells secrete factors that enhance EVT invasion | 7–12-week decidua |
| Zhang et al. (113) | 2013 | Downregulation of uNK cell VEGF expression abrogates EVT migration | 6–20-week decidua |
| Wallace et al. (93) | 2015 | uNK cells from pregnancies with high umbilical artery resistance have decreased expression of HLA-binding cell-surface receptors | 9–14-week decidua |
| Tilburgs (143) | 2015 | A single EVT forms synapses with several uNK cells | 6–12-week decidua |
| Ma (109) | 2017 | uNK cell conditioned medium promotes trophoblast invasion and endothelial cell tube formation | 6–10-week decidua |
Note: ECM = extracellular matrix; EVT = extravillous trophoblast; HLA = human leukocyte antigen; IL = interleukin; MMPs = matrix metalloproteinases; uNK = uterine natural killer; VEGF = vascular endothelial growth factor.