Abstract

Limited 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.

Details

Title
Mid-pregnancy poly(I:C) viral mimic disrupts placental ABC transporter expression and leads to long-term offspring motor and cognitive dysfunction
Author
Monteiro, V. R. S. 1 ; Andrade, C. B. V. 2 ; Gomes, H. R. 1 ; Reginatto, M. W. 1 ; Império, G. E. 3 ; Fontes, K. N. 1 ; Spiess, D. A. 1 ; Rangel-Junior, W. S. 1 ; Nascimento, V. M. O. 1 ; Lima, C. O. S. 1 ; Sousa, R. P. C. 1 ; Bloise, F. F. 1 ; Matthews, S. G. 4 ; Bloise, E. 5 ; Pimentel-Coelho, P. M. 1 ; Ortiga-Carvalho, T. M. 1 

 Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brasil (GRID:grid.8536.8) (ISNI:0000 0001 2294 473X) 
 Universidade Estadual Do Rio de Janeiro, Departamento de Histologia e Embriologia, Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro, Brasil (GRID:grid.412211.5) (ISNI:0000 0004 4687 5267) 
 Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada (GRID:grid.416166.2) (ISNI:0000 0004 0473 9881) 
 Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada (GRID:grid.416166.2) (ISNI:0000 0004 0473 9881); University of Toronto, Department of Physiology, Faculty of Medicine, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); University of Toronto, Department of Obstetrics and Gynaecology, Faculty of Medicine, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); University of Toronto, Department of Medicine, Faculty of Medicine, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938) 
 Universidade Federal de Minas Gerais, Departamento de Morfologia, Belo Horizonte, Brasil (GRID:grid.8430.f) (ISNI:0000 0001 2181 4888) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2677958019
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.