Mid-pregnancy poly(I:C) viral mimic disrupts placental ABC transporter expression and leads to long-term offspring motor and cognitive dysfunction.

Autor: Monteiro VRS; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Andrade CBV; Departamento de Histologia e Embriologia, Instituto de Biologia Roberto Alcantara Gomes, Universidade Estadual Do Rio de Janeiro, Rio de Janeiro, Brasil., Gomes HR; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Reginatto MW; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Império GE; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada., Fontes KN; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Spiess DA; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Rangel-Junior WS; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Nascimento VMO; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Lima COS; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Sousa RPC; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Bloise FF; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Matthews SG; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada.; Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Toronto, Toronto, Canada.; Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada., Bloise E; Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil., Pimentel-Coelho PM; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Ortiga-Carvalho TM; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. taniaort@biof.ufrj.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Jun 17; Vol. 12 (1), pp. 10262. Date of Electronic Publication: 2022 Jun 17.
DOI: 10.1038/s41598-022-14248-0
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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