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单细胞转录组分析揭示了薄型子宫内膜的分子和细胞特征。

Single-cell transcriptome analysis uncovers the molecular and cellular characteristics of thin endometrium.

机构信息

Department of Obstetrics and Gynecology, Qingdao Medical College of Qingdao University, Qingdao, China.

Center for Reproductive Medicine, Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.

出版信息

FASEB J. 2022 Mar;36(3):e22193. doi: 10.1096/fj.202101579R.

Abstract

Infertility is a social and medical problem around the world and the incidence continues to rise. Thin endometrium (TE) is a great challenge of infertility treatment, even by in vitro fertilization and embryo transfer. It is widely believed that TE impairs endometrium receptivity. However, only a few studies have explained the molecular mechanism. Herein, in order to reveal the possible mechanism, we sampled endometrium from a TE patient and a control volunteer and got a transcriptomic atlas of 18 775 individual cells which was constructed using single-cell RNA sequencing, and seven cell types have been identified. The cells were acquired during proliferative and secretory phases, respectively. The proportion of epithelial cells and stromal cells showed a significant difference between the TE group and the control group. In addition, differential expressed genes (DEGs) in diverse cell types were revealed, the enriched pathways of DEGs were found closely related to the protein synthesis in TE of both proliferative and secretory phases. Some DEGs can influence cell-type ratio and impaired endometrial receptivity in TE. Furthermore, divergent expression of estrogen receptors 1 and progesterone receptors in stromal and epithelial cells were compared in the TE sample from the control. The cellular and molecular heterogeneity found in this study provided valuable information for disclosing the mechanisms of impaired receptivity in TE.

摘要

不孕是一个全球性的社会和医学问题,其发病率持续上升。薄型子宫内膜(TE)是不孕治疗的巨大挑战,即使采用体外受精和胚胎移植也是如此。人们普遍认为,TE 会损害子宫内膜的容受性。然而,只有少数研究解释了其分子机制。为此,我们从一位 TE 患者和一位对照志愿者的子宫内膜中取样,并使用单细胞 RNA 测序构建了 18775 个个体细胞的转录组图谱,鉴定出了 7 种细胞类型。这些细胞分别取自增殖期和分泌期。TE 组和对照组的上皮细胞和基质细胞比例有显著差异。此外,揭示了不同细胞类型中的差异表达基因(DEGs),富集途径与增殖期和分泌期 TE 中的蛋白质合成密切相关。一些 DEGs 可以影响细胞类型比例,并损害 TE 中的子宫内膜容受性。此外,还比较了 TE 样本中基质细胞和上皮细胞中雌激素受体 1 和孕激素受体的差异表达。本研究中发现的细胞和分子异质性为揭示 TE 中容受性受损的机制提供了有价值的信息。

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