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

Abstract

Objectives: Zika virus (ZIKV) congenital infection has been linked tosevere birth defects, especially in the CNS. Recent in vivo studiesfound that placental structure is damaged after ZIKV infection, whichmight be responsible for spontaneous abortions and fetal growth restriction.However, it is still unknown how in utero ZIKV infection ismodulated by different environmental factors that could explain theasymmetrical distribution of malformations found along human populationsinfected with ZIKV. As part of a project analyzing the effectsof maternal undernutrition in a murine model of ZIKV infection, theaim of this study was to analyze histological and ultrastructuralchanges induced in the placenta by the combined action of proteinrestriction and ZIKV.Methods: C57BL/6 nulliparous female mice were fed by either a control(Co) diet with 20% protein content or an isocaloric low protein (LP) dietwith 6% of protein. Administration of both diets started 7-10 days beforemating and continued until E15. Infection was performed on E12 byintraperitoneal injection. Resulting experimental groups were: Co/Mock(Control diet, non-infected), Co/ZIKV (Control diet, ZIKV), LP/Mock (Lowprotein diet, non-infected), LP/ZIKV (Low protein/ZIKV). E15 placentaewere fixed in 4% paraformaldehyde for H&E and PAS-staining or inglutaraldehyde for high resolution optic (HRLM) and transmission electronmicroscopy (TEM).Results: While the junctional zone (JZ) of placentae from Co/ZIKV and LP/Mock was slightly altered, the JZ from LP/ZIKV was disorganized, hadmarked cell death and wide maternal blood spaces compared to Co/Mock.The labyrinth of LP/ZIKV was disorganized with poor trophoblastic adhesion,abundant necrosis and vascular alterations as maternal hemorrhage.By TEM analysis, the most important lesions corroborated in LP/ZIKVgroup were the cytoplasmic vacuolization and loss of labyrinthinetrophoblastic chromatin material.Conclusion: The combined effect of maternal undernutrition and ZIKVenhances placental structural damage with potential consequences in thedeveloping offspring.