Fu Xiaoying, Guo Xiaoyan, Xu Han, Li Yini, Jin Bihui, Zhang Xirong, Shu Chongyi, Fan Yuhang, Yu Yiqi, Tian Yuqing, Tian Jiao, Shu Jing
Center for Reproductive Medicine, Department of Reproductive Endocrinology, Affiliated People's Hospital, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Center for Reproductive Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Reprod Biol Endocrinol. 2024 Jul 31;22(1):90. doi: 10.1186/s12958-024-01263-1.
Reduced endometrium thickness and receptivity are two important reasons for recurrent implantation failure (RIF). In order to elucidate differences between these two types of endometrial defects in terms of molecular signatures, cellular interactions, and structural changes, we systematically investigated the single-cell transcriptomic atlas across three distinct groups: RIF patients with thin endometrium (≤ 6 mm, TE-RIF), RIF patients with normal endometrium thickness (≥ 8 mm, NE-RIF), and fertile individuals (Control).
The late proliferative and mid-secretory phases of the endometrium were collected from three individuals in the TE-RIF group, two in the NE-RIF group, and three in the control group. The study employed a combination of advanced techniques. Single-cell RNA sequencing (scRNA-seq) was utilized to capture comprehensive transcriptomic profiles at the single-cell level, providing insights into gene expression patterns within specific cell types. Scanning and transmission electron microscopy were employed to visualize ultrastructural details of the endometrial tissue, while hematoxylin and eosin staining facilitated the examination of tissue morphology and cellular composition. Immunohistochemistry techniques were also applied to detect and localize specific protein markers relevant to endometrial receptivity and function.
Through comparative analysis of differentially expressed genes among these groups and KEGG pathway analysis, the TE-RIF group exhibited notable dysregulations in the TNF and MAPK signaling pathways, which are pivotal in stromal cell growth and endometrial receptivity. Conversely, in the NE-RIF group, disturbances in energy metabolism emerged as a primary contributor to reduced endometrial receptivity. Additionally, using CellPhoneDB for intercellular communication analysis revealed aberrant interactions between epithelial and stromal cells, impacting endometrial receptivity specifically in the TE-RIF group.
Overall, our findings provide valuable insights into the heterogeneous molecular pathways and cellular interactions associated with RIF in different endometrial conditions. These insights may pave the way for targeted therapeutic interventions aimed at improving endometrial receptivity and enhancing reproductive outcomes in patients undergoing ART. Further research is warranted to validate these findings and translate them into clinical applications for personalized fertility treatments.
Not applicable.
子宫内膜厚度降低和容受性下降是反复种植失败（RIF）的两个重要原因。为了阐明这两种类型的子宫内膜缺陷在分子特征、细胞相互作用和结构变化方面的差异，我们系统地研究了三个不同组别的单细胞转录组图谱：子宫内膜薄（≤6mm）的RIF患者（TE-RIF）、子宫内膜厚度正常（≥8mm）的RIF患者（NE-RIF）和有生育能力的个体（对照组）。
从TE-RIF组的3名个体、NE-RIF组的2名个体和对照组的3名个体中收集子宫内膜的增殖晚期和分泌中期样本。本研究采用了多种先进技术相结合的方法。利用单细胞RNA测序（scRNA-seq）在单细胞水平上捕获全面的转录组图谱，深入了解特定细胞类型内的基因表达模式。采用扫描电子显微镜和透射电子显微镜观察子宫内膜组织的超微结构细节，苏木精-伊红染色有助于检查组织形态和细胞组成。还应用免疫组织化学技术检测和定位与子宫内膜容受性和功能相关的特定蛋白质标志物。
通过对这些组间差异表达基因的比较分析和KEGG通路分析，TE-RIF组在TNF和MAPK信号通路中表现出明显的失调，这两条通路在基质细胞生长和子宫内膜容受性中起关键作用。相反，在NE-RIF组中，能量代谢紊乱是子宫内膜容受性降低的主要原因。此外，使用CellPhoneDB进行细胞间通讯分析发现，上皮细胞和基质细胞之间存在异常相互作用，这在TE-RIF组中对子宫内膜容受性产生了特异性影响。
总体而言，我们的研究结果为不同子宫内膜条件下与RIF相关的异质分子途径和细胞相互作用提供了有价值的见解。这些见解可能为旨在改善子宫内膜容受性和提高接受辅助生殖技术（ART）治疗患者生殖结局的靶向治疗干预铺平道路。有必要进行进一步的研究来验证这些发现，并将其转化为个性化生育治疗的临床应用。
不适用。
