Abstract：
Although several testicular alterations promoted by coronavirus infection have been demonstrated, the extent, causes, and players of testicular pathogenesis are not totally understood. The present study aimed to investigate the short-term effects on male fertility of intranasally administered murine hepatitis virus strain 3 (MHV-3), a member of the genus Betacoronavirus, which causes a severe systemic acute infection. This mouse model might be used as a in vivo prototype for investigating the impact of betacoronavirus on the endocrine and exocrine testicular functions with the advantage to be performed in a biosafety level 2 condition. Herein, we performed virological, histopathological, and molecular studies regarding the testicular spermatogenesis and the spermatic quality analyses in an MHV-3-infected C57BL/6 mice. The main outcomes showed that MHV-3 infects mouse testis and induces a testicular inflammatory state, impairing the steroidogenic pathway. The infection led to several alterations in the testicular parenchyma, such as: seminiferous epithelium sloughing, retention of residual bodies, germ cell apoptosis, alterations in intercellular junction proteins, and worse spermatogenic parameters. Moreover, the levels of plasmatic testosterone as well as the quality of sperm production reduced. Therefore, the present data suggest that the viral/inflammatory impairment of the steroidogenic pathway and the consequent imbalance of androgen levels is critical in testicular pathology, disturbing the SC barrier function and the germ cell differentiation. Our study is important for comprehending the effects of beta coronavirus infections on testis function in order to develop treatments that could prevent virus-mediated male infertility.
摘要：
尽管已经证明了冠状病毒感染促进的几种睾丸改变，程度,原因,睾丸发病机制的参与者还没有完全理解。本研究旨在研究对男性生育能力的短期影响鼻内给药鼠肝炎病毒株3（MHV-3），Betacoronavirus属的成员，导致严重的全身急性感染。该小鼠模型可用作体内原型，用于研究β冠状病毒对内分泌和外分泌睾丸功能的影响，并具有在生物安全性2级条件下进行的优势。在这里，我们进行了病毒学，组织病理学,以及有关MHV-3感染的C57BL/6小鼠睾丸精子发生和精子质量分析的分子研究。主要结果显示MHV-3感染小鼠睾丸并诱导睾丸炎症状态,损害类固醇生成途径。感染导致睾丸实质的一些改变，如:生精上皮脱落，残体的保留，生殖细胞凋亡，细胞间连接蛋白的改变，和更差的生精参数。此外，血浆睾酮水平以及精子生产质量降低。因此,目前的数据表明，类固醇生成途径的病毒/炎症损害以及随之而来的雄激素水平失衡在睾丸病理学中至关重要。干扰SC屏障功能和生殖细胞分化。我们的研究对于理解β冠状病毒感染对睾丸功能的影响，以开发可以预防病毒介导的男性不育的治疗方法非常重要。
