Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Intranasal or Intratesticular Route Induces Testicular Damage
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Intranasal or Intratesticular Route Induces Testicular Damage
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DOI：
10.1093/cid/ciac142
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发表时间：
2022-02-18
影响因子：
11.8
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
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作者：
Li, Can;Ye, Zhanhong;Yuen, Kwok-Yung
背景 严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 在睾丸损伤发病机制中的作用尚不确定。方法 我们以甲型H1N1流感病毒pdm09为对照，通过鼻内或直接睾丸接种，研究了野生型SARS-CoV-2及其变种攻击仓鼠睾丸的病毒学、病理学和免疫学变化。结果 除了自限性呼吸道感染外，鼻内SARS-CoV-2攻击还导致感染后4-7天精子数量、血清睾酮和抑制素B急剧下降；感染后 42-120 天睾丸大小和重量以及血清性激素慢性减少。随着病毒接种量的增加，出现急性组织病理学损伤，包括睾丸炎症程度加重、出血、坏死、生精小管变性以及有序精子发生的破坏。发现支持细胞和间质细胞变性和死亡。尽管睾丸中的病毒载量和 SARS-CoV-2 核衣壳蛋白表达明显低于肺组织，但直接睾丸内注射 SARS-CoV-2 显示间质细胞和附睾上皮细胞表达核衣壳，而 A(H1N1)pdm09 对照的鼻内或睾丸内攻击未显示睾丸感染或损伤。感染后7至120天，生精小管变性和凋亡、免疫复合物沉积以及生精细胞和精子的耗竭持续存在。 Omicron 和 Delta 变体的鼻内攻击也可能引起类似的睾丸变化。这种睾丸损伤可以通过疫苗接种来预防。结论 尽管仓鼠患有自限性肺炎，但 SARS-CoV-2 仍可引起急性睾丸损伤，并随后导致慢性不对称睾丸萎缩和相关的激素变化。对可能的性腺功能减退和生育能力低下的认识对于管理男性恢复期 2019 年冠状病毒病非常重要。尽管仓鼠患有自限性肺炎，但严重急性呼吸综合征冠状病毒 2 型鼻内感染仍会导致睾丸损伤和相关的激素变化。对可能的性腺功能减退症和生育能力低下的认识对于管理男性恢复期 2019 年冠状病毒病非常重要。
Background The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pathogenesis of testicular damage is uncertain. Methods We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by wild-type SARS-CoV-2 and its variants with intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control. Results Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, serum testosterone and inhibin B at 4-7 days after infection; and chronic reduction in testicular size and weight, and serum sex hormone at 42-120 days after infection. Acute histopathological damage with worsening degree of testicular inflammation, hemorrhage, necrosis, degeneration of seminiferous tubules, and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and death of Sertoli and Leydig cells were found. Although viral loads and SARS-CoV-2 nucleocapsid protein expression were markedly lower in testicular than in lung tissues, direct intratesticular injection of SARS-CoV-2 demonstrated nucleocapsid expressing interstitial cells and epididymal epithelial cells, While intranasal or intratesticular challenge by A(H1N1)pdm09 control showed no testicular infection or damage. From 7 to 120 days after infection, degeneration and apoptosis of seminiferous tubules, immune complex deposition, and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. This testicular damage can be prevented by vaccination. Conclusions SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent coronavirus disease 2019 in men.Severe acute respiratory syndrome coronavirus 2 intranasal infection causes testicular damage and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent coronavirus disease 2019 in males.