Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, People's Republic of China.
NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, People's Republic of China.
Theranostics. 2022 Sep 6;12(15):6527-6547. doi: 10.7150/thno.74053. eCollection 2022.
Despite great advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) cannot be effectively avoided. Notably, cellular characteristics and communication that regulate endometrial receptivity and differentiation, and its disorders in RIF at window of implantation (WOI) remain rudimentary. In this study, we profiled the endometrial cells present at the WOI timing in RIF patients and healthy controls using single-cell RNA sequencing (scRNA-seq) and provided a detailed molecular and cellular map of a healthy and RIF endometrium at the WOI. In the current study, the endometrium from RIF patient (n = 6; age range, 32 - 35 years) and control (Ctrl) (n = 3; age range, 29 - 35 years) groups were studied at a single-cell resolution. single-cell RNA-seq and analysis were performed on the endometrium of patients with RIF and Ctrl. Immunofluorescence, flow cytometry assays, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to verify cellular identity and function. We profiled the transcriptomes of 60222 primary human endometrial cells isolated from control and RIF patients at a single-cell resolution. We discovered dramatic differential expression of endometrial receptivity-related genes in four major endometrial fibroblast-like cells from RIF patients compared to the control endometrium. We observed that CD49aCXCR4NK cells were diminished in proportion with RIF. The decrease in subset of CD63PGR endometrial epithelial cells with high levels of progesterone receptor, autophagy and exosomes should contribute to the decrease in subset of NK cells. Additionally, we characterized aberrant molecular and cellular characteristics and endometrial cell-cell communication disorders in RIF patients. Our study provides deeper insights into endometrial microenvironment disorder of RIF that are potentially applicable to improving the etiological diagnosis and therapeutics of unexplained RIF.
尽管辅助生殖技术(ART)取得了重大进展,但反复着床失败(RIF)仍无法有效避免。值得注意的是,调节子宫内膜容受性和分化的细胞特征和通讯,以及其在着床窗口期(WOI)的紊乱,仍然很基础。在这项研究中,我们使用单细胞 RNA 测序(scRNA-seq)对 RIF 患者和健康对照组的 WOI 时间点的子宫内膜细胞进行了分析,并提供了 WOI 时健康和 RIF 子宫内膜的详细分子和细胞图谱。在本研究中,我们以单细胞分辨率研究了 RIF 患者(n = 6;年龄范围,32-35 岁)和对照组(Ctrl)(n = 3;年龄范围,29-35 岁)组的子宫内膜。对 RIF 和 Ctrl 患者的子宫内膜进行了单细胞 RNA-seq 分析。进行了免疫荧光、流式细胞术检测和定量实时聚合酶链反应(qRT-PCR)以验证细胞的身份和功能。我们以单细胞分辨率对来自对照和 RIF 患者的 60222 个原发性人子宫内膜细胞的转录组进行了分析。我们发现,与对照子宫内膜相比,RIF 患者的四种主要子宫内膜成纤维细胞样细胞中,子宫内膜容受性相关基因的表达存在显著差异。我们观察到,与 RIF 相比,CD49aCXCR4NK 细胞的比例减少。具有高水平孕激素受体、自噬和外泌体的 CD63PGR 子宫内膜上皮细胞亚群的减少,可能导致 NK 细胞亚群的减少。此外,我们还描述了 RIF 患者异常的分子和细胞特征以及子宫内膜细胞间通讯紊乱。我们的研究提供了对 RIF 子宫内膜微环境紊乱的更深入了解,这可能有助于改善不明原因 RIF 的病因诊断和治疗。
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