The pathological damage in testicular tissue of Syrian golden hamster associated with SARS-CoV-2 infection

Abstract

We previously found that wild-type SARS-CoV-2 infection of hamster model led to testicular damage in addition to respiratory tissue damages, and the testicular tissue damage lasted until 120 days post infection. However, whether the later SARS-CoV-2 variant could also cause similar damage to testis and the underlying pathogenic mechanism are largely unknown. In this study, we employed hamster models to study the testicular damage induced by Omicron BA.5 infection. We found that BA.5 caused mild testicular histological changes at 4 dpi. Similar to wild-type SARS-CoV-2 infection, BA.5 infection resulted in a decreased sperm cells count, reduced testes weight and size accompanied with reduced serum testosterone and increased FSH at 42 days post infection. Histological examination showed extensive cell necrosis and depletion of spermatogenic cells. Furthermore, in vivo and ex vivo experiments was conducted to elucidate the mechanism of testicular damage caused by SARS-CoV-2. Intratesticular injection of SARS-CoV-2 showed only a few virus positive cells in the interstitial tissue regardless of the expression of ACE2 and TMPRSS2 in the testicular tissue. Ex vivo inoculation of SARS-CoV-2 in the isolated testicular cells further verified that testicular cells do not support the replication of SARS-CoV-2. These findings indicated that direct virus infection of testis tissue is unlikely the cause. Importantly, we found IgG deposition in seminiferous tubules of Omicron BA.5-infected hamsters at the chronic stage. Besides, antibodies that binds testicular proteins could be detected in the serum of SARS-CoV-2-infected hamsters. These results suggest that autoimmune mechanism may play a role on the pathological damage in testicular tissue of the infected hamsters.