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Suggestions on cleavage embryo and blastocyst vitrification/transfer based on expression profile of ACE2 and TMPRSS2 in current COVID‐19 pandemic
Molecular Reproduction and Development ( IF 2.7 ) Pub Date : 2021-02-24 , DOI: 10.1002/mrd.23456
Gui-Ping Cheng 1 , Shi-Meng Guo 1 , Li-Quan Zhou 1
Affiliation  

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is leading to an unprecedented worldwide health crisis. SARS‐CoV‐2 cell entry depends on ACE2 and TMPRSS2. Our objectives are to analysis the expression profile of ACE2 and TMPRSS2 in human spermatogenic cells, follicle cells, and preimplantation embryos, thereby providing mechanistic insights into viral entry and viral impact on reproduction. We found that ACE2 is mainly expressed during gametogenesis in spermatogonia and oocytes of antral follicles, granulosa cells of antral follicles and pre‐ovulatory follicles, while TMPRSS2 almost has no expression in spermatogenic cells, oocytes or granulosa cells. In preimplantation embryos, ACE2 is expressed in early embryos before eight‐cell stage, and trophectoderm of late blastocysts, while TMPRSS2 initiates its robust expression in late blastocyst stage. ACE2 and TMPRSS2 only show significant co‐expression in trophectoderm of late blastocysts in all above cell types. We speculate that trophectoderm of late blastocysts is susceptible to SARS‐CoV‐2, and that the chance of SARS‐CoV‐2 being passed on to offspring through gametes is very low. Therefore, we propose that fertility preservation for COVID‐19 patients is relatively safe and rational. We also recommend embryo cryopreservation and embryo transfer into healthy recipient mother at cleavage stage instead of blastocyst stage. Moreover, we unexpectedly found that co‐expression pattern of ACE2 and TMPRSS2 in oocytes and preimplantation embryos in human, rhesus monkey and mouse are totally different, so animal models have significant limitations for evaluating transmission risk of SARS‐CoV‐2 in reproduction.

中文翻译:

当前 COVID-19 大流行中基于 ACE2 和 TMPRSS2 表达谱的卵裂胚胎和囊胚玻璃化/移植建议

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的爆发正在导致前所未有的全球健康危机。SARS-CoV-2 进入细胞依赖于ACE2TMPRSS2。我们的目标是分析ACE2TMPRSS2在人类生精细胞、卵泡细胞和植入前胚胎中的表达谱,从而提供病毒进入和病毒对生殖影响的机制见解。我们发现ACE2主要在配子发生过程中在精原细胞和窦卵泡卵母细胞、窦卵泡颗粒细胞和排卵前卵泡中表达,而TMPRSS2在生精细胞、卵母细胞或颗粒细胞中几乎不表达。在植入前胚胎中,ACE2在八细胞期之前的早期胚胎和晚期囊胚的滋养外胚层中表达,而TMPRSS2在晚期囊胚阶段开始强烈表达。ACE2TMPRSS2仅在所有上述细胞类型的晚期囊胚的滋养外胚层中表现出显着的共表达。我们推测晚期囊胚的滋养外胚层对 SARS-CoV-2 敏感,并且 SARS-CoV-2 通过配子遗传给后代的机会非常低。因此,我们认为对COVID-19患者保留生育力是相对安全合理的。我们还建议在卵裂期(而不是囊胚期)将胚胎冷冻保存并移植到健康的受体母亲体内。此外,我们意外地发现,人类、恒河猴和小鼠的卵母细胞和植入前胚胎中ACE2TMPRSS2的共表达模式完全不同,因此动物模型在评估SARS-CoV-2在生殖中的传播风险方面具有显着的局限性。
更新日期:2021-03-25
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