Liu Anna, Ruetalo Natalia, Raja Xavier Janet P, Lankapalli Aditya Kumar, Admard Jakob, Camarena-Sainz Miguel, Brucker Sara Y, Singh Yogesh, Schindler Michael, Salker Madhuri S
Department of Women's Health, Eberhard-Karls University Tuebingen, Calwerstr. 7/6, 72076 Tuebingen, Germany.
Institute for Medical Virology, Department of Molecular Virology, University Hospital Tuebingen, Elfriede-Aulhorn-Str. 6, 72076 Tuebingen, Germany.
Clin Sci (Lond). 2025 Feb 19;139(4):CS20241215. doi: 10.1042/CS20241215.
Vertical transmission of SARS-CoV-2 during human pregnancy remains highly controversial as most studies have focused on the third trimester or the peripartum period. Given the lack of early trimester data, determining the prevalence of vertical transmission during early pregnancy and assessing the potential risks for fetal morbidity and mortality pose a challenge. Therefore, we analysed the impact of SARS-CoV-2 infection on an endometrial 3D spheroid model system. The 3D spheroids are capable of decidualization and express angiotensin-converting enzyme 2 (ACE2) as well as transmembrane protease serine 2 (TMPRSS2), rendering them susceptible to SARS-CoV-2 infection. Employing this 3D cell model, we identified that SARS-CoV-2 can infect both non-decidualized and decidualized endometrial spheroids. Infection significantly increased the chemokine Monocyte chemoattractant protein-1 (MCP-1) compared to non-infected spheroids. Decidualized spheroids exhibited upregulated Interleukin (IL)-8 levels. Furthermore, RNA sequencing revealed dysregulation of several genes involved in tissue-specific immune response, Fc receptor signalling, angiotensin-activated signalling and actin function. Gene expression changes varied between SARS-CoV-2 infected non-decidualized and decidualized spheroids and genes associated with the innate immune system (CD38, LCN2 and NR4A3) were dysregulated as a potential mechanism for immune evasion of SARS-CoV-2. Altogether, our study demonstrates that endometrial spheroids are a useful model to examine the clinical implications of SARS-CoV-2 vertical transmission, warranting further investigations.
SARS-CoV-2在人类孕期的垂直传播仍极具争议，因为大多数研究都集中在孕晚期或围产期。鉴于缺乏孕早期的数据，确定孕早期垂直传播的发生率以及评估胎儿发病和死亡的潜在风险是一项挑战。因此，我们分析了SARS-CoV-2感染对子宫内膜三维球体模型系统的影响。三维球体能够发生蜕膜化，并表达血管紧张素转换酶2（ACE2）以及跨膜蛋白酶丝氨酸2（TMPRSS2），使其易受SARS-CoV-2感染。利用这个三维细胞模型，我们发现SARS-CoV-2可以感染未蜕膜化和已蜕膜化的子宫内膜球体。与未感染的球体相比，感染显著增加了趋化因子单核细胞趋化蛋白-1（MCP-1）。已蜕膜化的球体白细胞介素（IL）-8水平上调。此外，RNA测序揭示了参与组织特异性免疫反应、Fc受体信号传导、血管紧张素激活信号传导和肌动蛋白功能的几个基因的失调。SARS-CoV-2感染的未蜕膜化和已蜕膜化球体之间的基因表达变化不同，与先天免疫系统相关的基因（CD38、LCN2和NR4A3）失调，这是SARS-CoV-2免疫逃逸的潜在机制。总之，我们的研究表明，子宫内膜球体是研究SARS-CoV-2垂直传播临床意义的有用模型，值得进一步研究。
