Author(s): Molás, Rafaela Batista [UNESP] ; Ribeiro, Milene Rocha [UNESP] ; Ramalho dos Santos, Maria Juliana C ; Borbely, Alexandre Urban ; Oliani, Denise Vaz ; Oliani, Antonio Hélio ; Nadkarni, Suchita ; Nogueira, Maurício Lacerda ; Moreli, Jusciele Brogin ; Oliani, Sonia Maria [UNESP]
Date: 2020
Persistent ID: http://hdl.handle.net/11449/201124
Origin: Oasisbr
Subject(s): Annexin A1; Human placenta; Inflammation; Leukocytes; Syncytiotrophoblast
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
The association of Zika virus infection (ZIKV) with congenital malformation and neurological sequelae brought a significant global concern. Recent studies have shown that maternal viral infection leads to inflammation in the placental tissue. In this context, the antiinflammatory protein annexin 1 (ANXA1) has a major determination of the resolution of inflammation and it has been positively associated with antiparasitic activity in infected placental explants. Although these effects have been explored to some degree, ANXA1 expression and potential properties have not yet been fully elucidated in placentas infected with ZIKV. This study was conducted to evaluate the histopathology, inflammatory process and elucidate if ANXA1 were differently expressed in placentas of ZIKV-infected mothers. Three classification groups were used in this study: Neg/Neg (mother and placenta negative for the virus), Pos/Neg (infected mother, but no virus detected in placenta) and Pos/Pos (mother and placenta infected with ZIKV). ANXA1 was expressed in syncytiotrophoblast cells of all studied groups, and its expression was decreased in Pos/Neg group, which displayed also an increase of the inflammatory response, as evinced from the recruitment of inflammatory cells, increased levels of placenta cytokines, and evidence of impaired tissue repair. The presence of ZIKV in placentas of Pos/Pos group shows structural alterations, including detachment and disorganization of the trophoblastic epithelium. In summary, our results suggest that maternal infection with ZIKV, even without direct tissue infection, leads to a placental inflammatory response probably related to the modulation of ANXA1. After placental infection, structural changes - including inflammatory cells influx - are observed leading to placental dysfunction and reduced fetal weight. Our study sheds additional light on the outcomes of ZIKV infection in trophoblast and reveals a potential involvement of ANXA1 in the placental biology.
Department of Biology School of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)
Cell Biology Laboratory Institute of Health and Biological Sciences Federal University of Alagoas
Department of Gynecology and Obstetrics São José Do Rio Preto School of Medicine (FAMERP)
The William Harvey Research Institute Barts and the London School of Medicine Queen Mary University of London
Department of Dermatological Infectious and Parasitic Diseases São José Do Rio Preto School of Medicine (FAMERP)
Faceres School of Medicine
Post-graduation in Structural and Functional Biology Federal University of São Paulo (UNIFESP)
Department of Biology School of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)
FAPESP: 2016/02012-4
FAPESP: 2017/09136-3
FAPESP: 2018/07895-7
CNPq: 308144/2014-7
