Biologia reprodutiva de machos adultos nascidos de mães infectadas por Zika Vírus

Abstract

Zika virus (ZIKV), belonging to the Flaviviridae family, is transmitted primarily by the bite of the Aedes aegypt mosquito. ZIKV causes an infection that is primarily asymptomatic or presents mild symptoms; however, infection of pregnant women results in cases of microcephaly in the offspring. Recently, our research group demonstrated that murine infants born from mothers infected during pregnancy present substantial testicular alterations. In this context, the present study aimed to investigate the presence of viral proteins and detail the causes of testicular alterations in mice born from mothers infected with ZIKV during gestation. Two experimental groups were created in which pregnant mice (at day 5.5 post-coitus) were exposed to PBS and ZIKV viral load (106 Plaque Forming Units). Twelve weeks after the offspring were born, viral proteins were investigated in the gonads, and biometric, testicular, hormonal, and gamete analyses were performed. Interestingly, ZIKV-exposed offspring showed NS1 protein in different testicular cells (mainly Leydig cells, Sertoli cells, and germ cells). The infected offspring showed lower testicular weight and anogenital index, consistent with the drastic reduction of the testicular steroidogenic pathway, compromising plasma and intratesticular testosterone production. In addition, we can mention the failure in the signaling of Leydig cells with Sertoli cells and macrophages. We observed defeats in the sperm differentiation phase (which is highly androgen-dependent), and as a consequence, we identified head defects, protamination failures, DNA fragmentation, and changes in the dielectric properties of spermatozoa. In the present study, we further demonstrate those sperm dielectric properties associated with artificial intelligence modeling are promising for establishing a rapid diagnostic test for sperm changes due to viral infection. The results obtained provide an essential warning of potential fertility problems in individuals born to ZIKV-infected mothers during pregnancy.