Qi Ruofan, Guan Rui, Cai Shengyun, Xu Mingjuan, Yang Wen-Jui, Wang Chi Chiu
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, China.
Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Front Genet. 2023 Oct 3;14:1246725. doi: 10.3389/fgene.2023.1246725. eCollection 2023.
To evaluate the dynamic expression profiling alterations of SARS-CoV-2-associated molecules within the fertile human endometrium throughout the menstrual cycle. Furthermore, to explore the inherent vulnerability of the endometrium to SARS-CoV-2 infection among women experiencing recurrent pregnancy failure, including both recurrent implantation failures (RIF) and recurrent pregnancy losses (RPL). The present study employed multiple datasets to investigate the expression patterns of SARS-CoV-2-associated genes. Firstly, a single-cell RNA-sequencing dataset comprising endometrial samples from 19 healthy women across the menstrual cycle was utilized. Additionally, two microarray datasets encompassing 24 women with RIF, and 24 women with RPL during the peri-implantation phase were included. To complement these analyses, immunohistochemical (IHC) staining was performed on endometrial samples collected from 30 women with RIF, 30 women with RPL, and 20 fertile controls recruited specifically during the implantation period. The investigation revealed a moderate expression percentage of CTSL (22%), TMPRSS4 (15%), FURIN (16%) and MX1 (9%) in endometrium. Conversely, the expression percentages of ACE2 (1%) and TMPRSS2 (4%) were relatively low. Notably, the expression of BSG exhibited an increment towards the window of implantation, reaching its peak during the middle secretary phase. Furthermore, a significant reduction ( < 0.05) in TMPRSS2 expression was observed in the RIF group compared to the control group. While the expression of BSG was significantly increased ( < 0.05) in the RPL group, findings that were corroborated by the IHC staining results. The findings of this study indicate a noteworthy upregulation of BSG expression in the endometrium of women with RPL. These results suggest an augmented susceptibility of endometrium to SARS-CoV-2 infection, potentially contributing to unfavorable pregnancy outcomes.
评估整个月经周期中可育人类子宫内膜内与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）相关分子的动态表达谱变化。此外，探讨复发性妊娠失败（包括反复种植失败（RIF）和反复妊娠丢失（RPL））女性子宫内膜对SARS-CoV-2感染的内在易感性。本研究采用多个数据集来研究与SARS-CoV-2相关基因的表达模式。首先，利用了一个单细胞RNA测序数据集，该数据集包含19名健康女性在整个月经周期的子宫内膜样本。此外，还纳入了两个微阵列数据集，分别涵盖24名在着床期患有RIF的女性和24名患有RPL的女性。为补充这些分析，对从30名患有RIF的女性、30名患有RPL的女性以及专门在着床期招募的20名可育对照者收集的子宫内膜样本进行了免疫组织化学（IHC）染色。调查显示，组织蛋白酶L（CTSL，22%）、跨膜丝氨酸蛋白酶4（TMPRSS4，15%）、弗林蛋白酶（FURIN，16%）和Mx蛋白1（MX1，9%）在内膜中的表达百分比适中。相反，血管紧张素转换酶2（ACE2，1%）和跨膜丝氨酸蛋白酶2（TMPRSS2，4%）的表达百分比相对较低。值得注意的是，基底细胞粘附分子（BSG）的表达朝着着床窗增加，在分泌中期达到峰值。此外，与对照组相比，RIF组中TMPRSS2的表达显著降低（<0.05）。而RPL组中BSG的表达显著增加（<0.05），免疫组织化学染色结果证实了这一发现。本研究结果表明，RPL女性子宫内膜中BSG表达有显著上调。这些结果表明子宫内膜对SARS-CoV-2感染的易感性增加，可能导致不良妊娠结局。
