Gladstone Institutes, San Francisco, CA, USA.
Zouves Fertility Center, Foster City, CA, USA.
Sci Rep. 2022 Sep 14;12(1):15451. doi: 10.1038/s41598-022-18906-1.
The spread of SARS-CoV-2 has led to a devastating pandemic, with infections resulting in a range of symptoms collectively known as COVID-19. The full repertoire of human tissues and organs susceptible to infection is an area of active investigation, and some studies have implicated the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood, and particularly the impact on early embryogenesis and establishment of a pregnancy are not known. In this work, we explore the susceptibility of early human embryos to SARS-CoV-2 infection. By using RNA-seq and immunofluorescence, we note that ACE2 and TMPRSS2, two canonical cell entry factors for SARS-CoV-2, are co-expressed in cells of the trophectoderm in blastocyst-stage preimplantation embryos. For the purpose of viral entry studies, we used fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, and we observe robust infection of trophectoderm cells. This permissiveness could be attenuated with blocking antibodies targeting S or ACE2. When exposing human blastocysts to the live, fully infectious SARS-CoV-2, we detected cases of infection that compromised embryo health. Therefore, we identify a new human target tissue for SARS-CoV-2 with potential medical implications for reproductive health during the COVID-19 pandemic and its aftermath.
SARS-CoV-2 的传播导致了一场毁灭性的大流行,感染导致了一系列被称为 COVID-19 的症状。人类组织和器官易受感染的全部范围是一个活跃的研究领域,一些研究表明生殖系统也是如此。COVID-19 对人类生殖的影响仍知之甚少,特别是对早期胚胎发生和妊娠建立的影响尚不清楚。在这项工作中,我们探讨了早期人类胚胎对 SARS-CoV-2 感染的易感性。通过使用 RNA-seq 和免疫荧光,我们注意到 ACE2 和 TMPRSS2 这两种 SARS-CoV-2 的经典细胞进入因子在囊胚期植入前胚胎的滋养外胚层细胞中共同表达。为了进行病毒进入研究,我们使用了带有 SARS-CoV-2 刺突(S)糖蛋白的荧光报告病毒假型,我们观察到滋养外胚层细胞的强烈感染。这种易感性可以通过针对 S 或 ACE2 的阻断抗体来减弱。当将活的、具有完全感染力的 SARS-CoV-2 暴露于人类囊胚时,我们检测到了一些感染病例,这些感染病例损害了胚胎的健康。因此,我们确定了 SARS-CoV-2 的一个新的人类靶组织,这对 COVID-19 大流行及其后果期间的生殖健康具有潜在的医学意义。