Second Affiliated Hospital, School of Medicine, Zhejiang University, Department of Reproductive Medicine, Hangzhou, China.
Ministry of Education (MOE) Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Front Endocrinol (Lausanne). 2023 Jul 12;14:1185147. doi: 10.3389/fendo.2023.1185147. eCollection 2023.
Autoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the endometrial receptivity remains to be elucidated. In this study, we used single-cell RNA sequencing (scRNA-seq) to dissect immune microenvironment in endometrium of AITD patients during window of implantation (WOI).
We collected CD45 immune cell populations of endometrium samples of unexplained infertile women with AITD (=3), as well as samples of AITD controls (=3). The cells were then processed with 10X Genomics Chromium for further analysis.
We characterized 28 distinct immune cell subtypes totally, and uncovered differences in the composition and gene expression patterns between AITD patients and controls. The proportions of T CD4, cNK, ILC3, T CD8 , T CD8 Cytotoxic and ILC3 cells were increased, and CD366 uNK1 was decreased in AITD patients. And the abnormal expression of and chemokines was observed in AITD patients. In addition, uNK and T CD8 Cytotoxic cells showed lower cytotoxicity but activation of immune response. Genes enriched in cell adhesion of ILC3 and Tregs were downregulated, while the number of ILC3 and Tregs were increased.
Immune imbalance exists in endometrium during WOI, which may impact embryo implantation.
自身免疫性甲状腺疾病（AITD）已知与女性不明原因不孕有关。虽然抗甲状腺抗体的存在被推测为导致着床失败的免疫失衡的标志物，但影响子宫内膜容受性的潜在机制仍有待阐明。在这项研究中，我们使用单细胞 RNA 测序（scRNA-seq）来剖析 AITD 患者着床窗口期（WOI）子宫内膜中的免疫微环境。
我们收集了 3 名患有 AITD 的不明原因不孕女性和 3 名 AITD 对照组的子宫内膜样本中的 CD45 免疫细胞群。然后，用 10X Genomics Chromium 对这些细胞进行进一步分析。
我们总共鉴定出 28 种不同的免疫细胞亚型，并发现 AITD 患者和对照组之间的组成和基因表达模式存在差异。AITD 患者的 T CD4、cNK、ILC3、T CD8、T CD8 细胞毒性和 ILC3 细胞的比例增加，而 CD366 uNK1 减少。并且在 AITD 患者中观察到异常表达的 和趋化因子。此外，uNK 和 T CD8 细胞毒性细胞表现出较低的细胞毒性但激活免疫反应。ILC3 和 Tregs 细胞黏附相关基因富集下调，而 ILC3 和 Tregs 数量增加。
在 WOI 期间，子宫内膜中存在免疫失衡，这可能会影响胚胎着床。
