Author:
Monteiro V. R. S.,Andrade C. B. V.,Gomes H. R.,Reginatto M. W.,Império G. E.,Fontes K. N.,Spiess D. A.,Rangel-Junior W. S.,Nascimento V. M. O.,Lima C. O. S.,Sousa R. P. C.,Bloise F. F.,Matthews S. G.,Bloise E.,Pimentel-Coelho P. M.,Ortiga-Carvalho T. M.
Abstract
AbstractLimited information is available about the effect of mid-pregnancy viral infections on the placental expression of efflux transporters and offspring behavior. We hypothesized that maternal exposure to polyinosinic-polycytidylic acid [poly(I:C)], a synthetic double-stranded RNA viral mimic, would impair placental cell turnover, the expression of selected ABC transporters and adult offspring behavior. C57BL/6 mice were administered poly(I:C) (10 mg/Kg;ip) or vehicle at gestational day (GD) 13.5 (mid-pregnancy). Dams were euthanized for blood collection 4 h after injection, fetal and placental collection at GD18.5 or allowed to deliver spontaneously at term. At GD 13.5, poly(I:C) induced an acute pro-inflammatory response characterized by an increase in maternal plasma levels of IL-6, CXCL-1 and CCL-2/MCP-1. At GD 18.5, poly(I:C) decreased cell proliferation/death in the labyrinthine and increased cell death in the junctional zones, characterizing a disruption of placental cell turnover. Abca1 and Abcg1 immunolabelling was decreased in the labyrinthine zone, whereas Abca1, Abcg1 and breast cancer resistance transporter (Bcrp) expression increased in the junctional zone. Moreover, adult offspring showed motor and cognitive impairments in the Rotarod and T-water maze tests. These results indicate that viral infection during mid-pregnancy may disrupt relevant placental efflux transporters, as well as placental cell turnover and offspring behavior in adult life.
Funder
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Canadian Institutes of Health Research
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Bill and Melinda Gates Foundation
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
Publisher
Springer Science and Business Media LLC
Cited by
10 articles.
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