Morphological lesions caused by ZIKV infection in the placenta of undernourished mouse dams

BARBEITO, CLAUDIO G.; BARBEITO - ANDRÉS, JIMENA; FERREIRA, J. C. C. G.; CRISTOFOLINI, A; FIORIMANTI, MR; HIGA, LUIZA M.; BELLIO, MARIA; TANURI, AMILCAR; MERKIS, C; CEBRAL, ELISA; GARCEZ, PATRICIA P.

Simposio; International Federation of Placenta Associations 2019; 2019

Objectives: Zika virus (ZIKV)congenital infection has been linked to severe birth defects, especially in theCNS. Recent in vivo studies found that placental structure is damaged afterZIKV infection, which might be responsible for spontaneous abortions and fetalgrowth restriction. However, it is still unknown how in utero ZIKV infection ismodulated by different environmental factors that could explain the asymmetricaldistribution of malformations found along human populations infected with ZIKV.As part of a project analyzing the effects of maternal undernutrition in amurine model of ZIKV infection, the aim of this study was to analyzehistological and ultrastructural changes induced in the placenta by thecombined action of protein restriction and ZIKV. Methods: C57BL/6 nulliparousfemale mice were fed by either a control (Co) diet with 20% protein content oran isocaloric low protein (LP) diet with 6% of protein. Administration of bothdiets started 7-10 days before mating and continued until E15. Infection wasperformed on E12 by intraperitoneal injection.Resulting experimental groups were: Co/Mock (Control diet, non-infected),Co/ZIKV (Control diet, ZIKV), LP/Mock (Low protein diet, non-infected), LP/ZIKV(Low protein/ZIKV). E15 placentae were fixed in 4% paraformaldehyde for H&Eand PAS-staining or in glutaraldehyde for high resolution optic (HRLM) andtransmission electron microscopy (TEM). Results: While the junctional zone (JZ)of placentae from Co/ZIKV and LP/Mock was slightly altered, the JZ from LP/ZIKVwas disorganized, had marked cell death and wide maternal blood spaces comparedto Co/Mock. The labyrinth of LP/ZIKV was disorganized with poor trophoblasticadhesion, abundant necrosis and vascular alterations as maternal hemorrhage. ByTEM analysis, the most important lesions corroborated in LP/ZIKV group were thecytoplasmic vacuolization and loss of labyrinthine trophoblastic chromatinmaterial. Conclusion: The combined effect of maternal undernutrition and ZIKV enhancesplacental structural damage with potential consequences in the developingoffspring.