Laboratory of Immunology, Institute of Pediatrics, Obstetrics and Gynecology Named After Academician O. Lukyanova of the National Academy of Medical Sciences of Ukraine, Mayborody St, 8, 04050, Kyiv, Ukraine.
"NADIYA" Clinic, Maksyma Kryvonosa St, 19a, 03037, Kyiv, Ukraine.
Placenta. 2023 Nov;143:62-68. doi: 10.1016/j.placenta.2023.10.002. Epub 2023 Oct 7.
Endometrial receptivity is largely determined by the immunophenotype of endometrium, especially uterine NK-cells (uNK). Immune component is directly involved in the formation of favourable microenvironment for the blastocyst implantation and placenta formation, but the way it changes during the maturation of endometrial tissue in healthy fertile women is still underexplored.
The endometrium was collected from 47 healthy oocyte donors after controlled ovarian stimulation: 23 women on the day of oocytes retrieval (OR) and 24 women on the term of implantation window (IW). The OR group was analysed, published previously and used as a comparison group to show the dynamic of changes. Isolated endometrial lymphocytes and peripheral blood samples were stained with monoclonal antibodies and analysed according to the three-color flow cytometry protocol.
The proportion of NK-cells (CD3CD56) in endometrium grew significantly in the implantation window compared to the oocytes retrieval day. NK-cells acquired a more differentiated phenotype from the day of OR until IW: the expression of CD8 and CD158a significantly increased, while the expression of HLA-DR significantly decreased. Significant correlations between peripheral blood and endometrial NK-cells were found in CD8 expression during OR and IW, CD335(p46)neg and CD335(p46)++ subsets during IW term.
Immunophenotype of receptive endometrium forms due to the accumulation of uNK-cells, which actively proliferate, become mature, differentiative, and ready to meet the embryo. Endometrial immunophenotype is peculiar and specific but not autonomic and isolated. Differentiation (CD8 on NK-cells), and activity (p46 on NK-cells) of peripheral blood lymphocytes is reflected in endometrial lymphocytes profile, and therefore the research of peripheral blood immunophenotype is relevant.
子宫内膜的接受性在很大程度上取决于子宫内膜的免疫表型，尤其是子宫自然杀伤细胞（uNK）。免疫成分直接参与为胚泡着床和胎盘形成创造有利的微环境，但在健康有生育能力的女性中，其在子宫内膜组织成熟过程中的变化方式仍未得到充分探索。
从 47 名接受控制性卵巢刺激的卵母细胞供体中采集子宫内膜：23 名妇女在取卵日（OR），24 名妇女在着床窗口期（IW）。分析了 OR 组，该组结果已发表并用作比较组，以显示变化的动态。分离子宫内膜淋巴细胞和外周血样本，用单克隆抗体染色，并根据三色流式细胞术方案进行分析。
与取卵日相比，着床窗口期子宫内膜中 NK 细胞（CD3CD56）的比例显著增加。NK 细胞从取卵日到着床窗口期获得了更分化的表型：CD8 和 CD158a 的表达显著增加，而 HLA-DR 的表达显著降低。在外周血和子宫内膜 NK 细胞中发现了在 OR 和 IW 期间 CD8 表达、在 IW 期间 CD335(p46)neg 和 CD335(p46)++亚群之间存在显著相关性。
接受性子宫内膜的免疫表型是由于 uNK 细胞的积累而形成的，uNK 细胞积极增殖、成熟、分化并准备迎接胚胎。子宫内膜免疫表型是独特和特异的，但不是自主和孤立的。外周血淋巴细胞的分化（NK 细胞上的 CD8）和活性（NK 细胞上的 p46）反映在子宫内膜淋巴细胞谱中，因此外周血免疫表型的研究是相关的。
