Medical Faculty, Department of Physiology and Immunology, University of Rijeka, Rijeka, Croatia.
Division of Rheumatology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism "Thalassotherapia" Opatija, Opatija, Croatia.
Am J Reprod Immunol. 2018 Sep;80(3):e12978. doi: 10.1111/aji.12978. Epub 2018 May 18.
Granulysin (GNLY) is a cytotoxic molecule mostly present in decidual natural killer (NK) cells. Blighted ovum (BO) and missed abortion (MA) represent the early pathological pregnancies with hindered development of the embryoblast or a dead embryo. We investigated the GNLY-mediated apoptotic mechanism potentially responsible for delayed termination of pregnancy.
We performed immunohistological and immunofluorescence labeling of decidual tissues (GNLY, Apaf-1, NF-κB). NKG2A expression was analyzed by flow cytometry and GNLY mRNA by RT-qPCR.
The GNLY labeling intensity (H score) was lower in the nuclei of trophoblast cells in BO and MA. GNLY gene levels were inversely detected in BO and MA. A decreased decidual NK cell percentage was found in MA. NK cells from pathological pregnancies expressed lower NKG2A levels. The highest frequency of Apaf-1 was found in trophoblast cells of MA. NF-kB was highly expressed in decidual cells of BO.
The reduced activation of GNLY-mediated killing might be implicated in the slower rejection of trophoblast cells in BO and MA. A decreased authentic decidual NK cell number could be responsible for low cytotoxicity against trophoblast cells in MA. In BO, trophoblast cells have a higher survival potential due to increased NF-kB expression.
颗粒溶素 (GNLY) 是一种主要存在于蜕膜自然杀伤 (NK) 细胞中的细胞毒性分子。枯萎卵 (BO) 和稽留流产 (MA) 代表了胚胎发育受阻或胚胎死亡的早期病理性妊娠。我们研究了可能导致妊娠终止延迟的 GNLY 介导的凋亡机制。
我们对蜕膜组织进行了免疫组织化学和免疫荧光标记 (GNLY、Apaf-1、NF-κB)。通过流式细胞术分析 NKG2A 表达，通过 RT-qPCR 分析 GNLY mRNA。
BO 和 MA 中滋养层细胞的 GNLY 标记强度（H 评分）较低。BO 和 MA 中检测到 GNLY 基因水平降低。MA 中存在较少的蜕膜 NK 细胞百分比。来自病理性妊娠的 NK 细胞表达较低水平的 NKG2A。MA 中 Apaf-1 的频率最高。BO 中的 NF-kB 在蜕膜细胞中高表达。
GNLY 介导的杀伤活性降低可能与 BO 和 MA 中滋养层细胞的较慢排斥有关。MA 中蜕膜 NK 细胞数量减少可能导致对滋养层细胞的细胞毒性降低。在 BO 中，由于 NF-kB 表达增加，滋养层细胞具有更高的生存潜力。
