Sfakianoudis Konstantinos, Rapani Anna, Grigoriadis Sokratis, Pantou Agni, Maziotis Evangelos, Kokkini Georgia, Tsirligkani Chrysanthi, Bolaris Stamatis, Nikolettos Konstantinos, Chronopoulou Margarita, Pantos Konstantinos, Simopoulou Mara
Centre for Human Reproduction, Genesis Athens Clinic, 14-16, Papanikoli, 15232 Athens, Greece.
Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece.
Biomedicines. 2021 Oct 9;9(10):1425. doi: 10.3390/biomedicines9101425.
Uterine natural killer (uNK) cells constitute a unique uterine leucocyte subpopulation facilitating implantation and maintaining pregnancy. Herein, we critically analyze current evidence regarding the role of uNK cells in the events entailed in recurrent implantation failure (RIF) and recurrent miscarriages (RM). Data suggest an association between RIF and RM with abnormally elevated uNK cells' numbers, as well as with a defective biological activity leading to cytotoxicity. However, other studies do not concur on these associations. Robust data suggesting a definitive causative relationship between uNK cells and RIF and RM is missing. Considering the possibility of uNK cells involvement on RIF and RM pathophysiology, possible treatments including glucocorticoids, intralipids, and intravenous immunoglobulin administration have been proposed towards addressing uNK related RIF and RM. When considering clinical routine practice, this study indicated that solid evidence is required to report on efficiency and safety of these treatments as there are recommendations that clearly advise against their employment. In conclusion, defining a causative relationship between uNK and RIF-RM pathologies certainly merits investigation. Future studies should serve as a prerequisite prior to proposing the use of uNK as a biomarker or prior to targeting uNK cells for therapeutic purposes addressing RIF and RM.
子宫自然杀伤（uNK）细胞构成了一个独特的子宫白细胞亚群，有助于着床和维持妊娠。在此，我们批判性地分析了关于uNK细胞在反复着床失败（RIF）和反复流产（RM）相关事件中作用的现有证据。数据表明，RIF和RM与uNK细胞数量异常升高以及导致细胞毒性的生物学活性缺陷之间存在关联。然而，其他研究并不认同这些关联。目前尚无有力数据表明uNK细胞与RIF和RM之间存在明确的因果关系。考虑到uNK细胞可能参与RIF和RM的病理生理过程，已提出了包括使用糖皮质激素、脂肪乳剂和静脉注射免疫球蛋白在内的可能治疗方法，以解决与uNK相关的RIF和RM问题。在考虑临床常规实践时，本研究表明，由于有明确建议反对使用这些治疗方法，因此需要确凿证据来报告这些治疗方法的有效性和安全性。总之，确定uNK与RIF - RM病理之间的因果关系无疑值得研究。在将uNK用作生物标志物或针对uNK细胞进行治疗以解决RIF和RM问题之前，未来的研究应作为前提条件。
