Zika virus (ZIKV) is a sexually transmitted viral infection most frequently transmitted by mosquitoes. The source of infectious virions in the male reproductive tract has yet to be elucidated. The goals of the studies included developing and characterizing two mouse models for reproductive transmission studies and demonstration of sexual transmission of virus via artificial insemination. The mouse strains used in the study lacked receptors to interferon molecules, key signaling proteins of the host immune response. Inflammation severity was assessed during acute disease, 5-11 days after infection using a novel histopathology grading system. ZIKV proteins and genome were initially detected in epididymal epithelial cells in males. Inflammation was first observed in the epididymis and progressed to the testicle in both AG129 and Ifnar-/- males. Infection of Ifnar-/- mice may better recapitulate Zika virus pathology in humans due to milder histopathologic lesions, the presence of histologically normal sperm in epididymal tubules, and an ability to survive the acute phase of disease. In further studies, male Ifnar-/- mice were challenged subcutaneously with ZIKV. Artificial insemination fluid derived from experimentally infected males showed positive sexual transmission at 7 days post infection (DPI) but not 35 or 70 DPI. These studies show passage of virus from epididymal flush and seminal plasma to females via insemination during acute ZIKV disease in males and provides a model for sexual transmission of ZIKV.

Orientador: Fabiana Ferreira de Souza / Resumo: Este estudo teve como objetivo avaliar os efeitos da ação imediata e por 10 dias consecutivos, da injeção intratesticular de 20% de CaCl2 associada a 0,5% de DMSO nas características espermáticas, na temperatura, biometria e histologia testicular, nas alterações macroscópicas do escroto e tecidos subjacentes, na proteômica do líquido epididimal e do espermatozóides, e nos efeitos tardios sobre a fertilidade em ratos Wistar. Foram utilizados 96 ratos machos e 24 fêmeas, com 80 a 90 dias de idade, respectivamente. Os machos foram divididos em dois grupos (controle e tratado), pesados e, as temperaturas corporal e escrotal aferidas (tempo 0). Os ratos receberam uma injeção intratesticular de 0,1 mL de NaCl a 0,9% (controle/CTR; n = 6) ou 0,1 mL de 20% de CaCl2 associado com 0,5% de DMSO (grupo tratado; n = 90); o grupo tratado foi dividido em 15 subgrupos, de acordo com o momento da eutanásia (2, 4, 8 e 12 h; D1-D10 e D100; n = 6/grupo). A temperatura corpórea e testicular, parâmetros seminais, biometria testicular, dor, avaliação testicular macroscópica e histológica foram realizadas às 2, 4, 8 e 12 h, a cada 24 h por 10 dias consecutivos e aos 100 dias. A análise proteômica dos espermatozóides foi realizada 2 h e D1, enquanto a proteômica do fluído epidimal às 2 h, D1, D5, D7 e D10. Aos 80 dias, os machos (CTR e tratado D100) foram pareados com 3 fêmeas para o teste de fertilidade. O tratamento com 20% de CaCl2 associado com 0,5% de DMSO prejudicou os parâmetros seminais com m... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study aimed to evaluate immediate effect of intratesticular injection of CaCl2 20% associated with DMSO 0.5% on sperm characteristics, testicular temperature, biometry and histology, macroscopic scrotal and adjacent tissue changes, epididymal fluid and spermatozoa proteomics, and the late effect of fertility on Wistar rats. We used 96 male and 24 female Wistar rats, 80 to 90 days old respectively. Males were divided into two groups (control and treated); weighed, and body and scrotal temperatures measured (time 0). Rats received an intratesticular injection of 0.1 mL of NaCl 0.9% (control/CTR; n = 6) or CaCl2 20% associated with DMSO 0.5% (treated group; n = 90); treated group was divided into 15 subgroups depending on euthanasia time (2, 4, 8 and 12 h; D1–D10 and D100; n = 6). Body and testicular temperature, seminal characteristics, testicular biometry, pain, macroscopic and histological testicular evaluations were performed at 2, 4, 8 and 12 h, every 24 h for 10 consecutive days and at 100 days. Spermatozoa proteomics analysis was done 2 h and D1 while epididymal fluid at 2 h, D1, D5, D7 and D10. At 80th day, male (CTR and treated D100) were couple with 3 female. The treatment with CaCl2 20% associated with DMSO 0.5% impaired seminal parameters with minimal systemic effects and increased scrotal temperature at 2, 4, 8 and 12 h in the treated group. At D100 was azoospermia, testicular atrophy and negative fertility test. Rats in the CTR group at D100 were normospermic ... (Complete abstract click electronic access below) / Doutor