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

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 imp...

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Published in:Scientific reports 2022-06, Vol.12 (1), p.10262-10262, Article 10262
Main Authors: 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.
Format: Article
Language:English
Subjects:
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ABC transporter
ABCA1 protein
ATP-binding protein
Breast cancer
Cell death
Cell proliferation
Cognitive ability
Double-stranded RNA
Fetuses
Humanities and Social Sciences
Inflammation
Interleukin 6
Maternal behavior
Monocyte chemoattractant protein 1
multidisciplinary
Offspring
Placenta
Plasma levels
Polyinosinic:polycytidylic acid
Pregnancy
Science
Science (multidisciplinary)
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-14248-0