PMID- 35715474 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20220819 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 12 IP - 1 DP - 2022 Jun 17 TI - Mid-pregnancy poly(I:C) viral mimic disrupts placental ABC transporter expression and leads to long-term offspring motor and cognitive dysfunction. PG - 10262 LID - 10.1038/s41598-022-14248-0 [doi] LID - 10262 AB - 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. CI - (c) 2022. The Author(s). FAU - Monteiro, V R S AU - Monteiro VRS AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Andrade, C B V AU - Andrade CBV AD - Departamento de Histologia e Embriologia, Instituto de Biologia Roberto Alcantara Gomes, Universidade Estadual Do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Gomes, H R AU - Gomes HR AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Reginatto, M W AU - Reginatto MW AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Imperio, G E AU - Imperio GE AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada. FAU - Fontes, K N AU - Fontes KN AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Spiess, D A AU - Spiess DA AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Rangel-Junior, W S AU - Rangel-Junior WS AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Nascimento, V M O AU - Nascimento VMO AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Lima, C O S AU - Lima COS AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Sousa, R P C AU - Sousa RPC AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Bloise, F F AU - Bloise FF AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Matthews, S G AU - Matthews SG AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada. AD - Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada. AD - Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Toronto, Toronto, Canada. AD - Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada. FAU - Bloise, E AU - Bloise E AD - Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil. FAU - Pimentel-Coelho, P M AU - Pimentel-Coelho PM AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Ortiga-Carvalho, T M AU - Ortiga-Carvalho TM AD - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. taniaort@biof.ufrj.br. LA - eng GR - 148368/CIHR/Canada GR - OPP1107597/GATES/Bill & Melinda Gates Foundation/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220617 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Membrane Transport Proteins) RN - 0 (Neoplasm Proteins) RN - O84C90HH2L (Poly I-C) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism MH - *ATP-Binding Cassette Transporters/metabolism MH - Animals MH - *Cognitive Dysfunction/metabolism MH - Female MH - Membrane Transport Proteins/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neoplasm Proteins/metabolism MH - Placenta/metabolism MH - Poly I-C/pharmacology MH - Pregnancy PMC - PMC9205917 COIS- The authors declare no competing interests. EDAT- 2022/06/18 06:00 MHDA- 2022/06/22 06:00 PMCR- 2022/06/17 CRDT- 2022/06/17 23:21 PHST- 2022/02/15 00:00 [received] PHST- 2022/06/03 00:00 [accepted] PHST- 2022/06/17 23:21 [entrez] PHST- 2022/06/18 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] PHST- 2022/06/17 00:00 [pmc-release] AID - 10.1038/s41598-022-14248-0 [pii] AID - 14248 [pii] AID - 10.1038/s41598-022-14248-0 [doi] PST - epublish SO - Sci Rep. 2022 Jun 17;12(1):10262. doi: 10.1038/s41598-022-14248-0.