PMID- 31391498 OWN - NLM STAT- MEDLINE DCOM- 20201027 LR - 20210110 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 9 IP - 1 DP - 2019 Aug 7 TI - Dysregulation of placental ABC transporters in a murine model of malaria-induced preterm labor. PG - 11488 LID - 10.1038/s41598-019-47865-3 [doi] LID - 11488 AB - Malaria in Pregnancy (MiP) is characterized by placental accumulation of Plasmodium-infected erythrocytes, intrauterine growth restriction (IUGR) and preterm delivery (PTD). Placental ATP-binding cassette (ABC) transporters mediate the efflux of nutrients, cytokines and xenobiotics. The expression and activity of these transporters are highly responsive to infection. We hypothesized that MiP would perturb the expression of placental ABC transporters, promoting PTD. Peripheral blood, spleens, livers and placentas of pregnant mice, infected with Plasmodium berghei ANKA on gestational day (GD) 13.5, were collected and analyzed on GD18.5. The primary consequences of human MiP, including IUGR, PTD (20%) and placental inflammation, were recapitulated in our mouse model. Electron microscopy revealed attenuated presence of labyrinthine microvilli and dilated spongiotrophoblasts -granular endoplasmic reticulum cisternae. Additionally, a decrease in placental Abca1 (ABCA1), Abcb1b (P-glycoprotein), Abcb9 and Abcg2 (BCRP) expression was observed in MiP mice. In conclusion, MiP associated with PTD impairs placental ABC transporters' expression, potentially modulating placental nutrient, environmental toxin and xenobiotic biodistribution within the fetal compartment, and may, at some degree, be involved with pregnancy outcome in MiP. FAU - Fontes, K N AU - Fontes KN AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Reginatto, M W AU - Reginatto MW AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Silva, N L AU - Silva NL AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Andrade, C B V AU - Andrade CBV AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Bloise, F F AU - Bloise FF AUID- ORCID: 0000-0002-5207-2896 AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Monteiro, V R S AU - Monteiro VRS AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Silva-Filho, J L AU - Silva-Filho JL AD - Laboratory of Immunology and Biochemistry of Parasitic Diseases, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. AD - Laboratory of Tropical Diseases, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, State University of Campinas, Campinas, Brazil. FAU - Imperio, G E AU - Imperio GE AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. AD - Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada. FAU - Pimentel-Coelho, P M AU - Pimentel-Coelho PM AD - Laboratory of Cellular and Molecular Neurobiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Pinheiro, A A S AU - Pinheiro AAS AD - Laboratory of Immunology and Biochemistry of Parasitic Diseases, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Matthews, S G AU - Matthews SG AD - Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada. AD - Department of Obstetrics & Gynaecology, Faculty of Medicine, University of Toronto, Toronto, Canada. AD - Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada. AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada. FAU - Bloise, E AU - Bloise E AD - Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil. FAU - Ortiga-Carvalho, T M AU - Ortiga-Carvalho TM AUID- ORCID: 0000-0002-0225-1132 AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. taniaort@biof.ufrj.br. LA - eng GR - 148368/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190807 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Xenobiotics) SB - IM MH - ATP-Binding Cassette Transporters/*metabolism MH - Animals MH - Disease Models, Animal MH - Female MH - Humans MH - Malaria/*complications/immunology/parasitology MH - Maternal-Fetal Exchange/immunology MH - Mice MH - Nutrients/metabolism MH - Obstetric Labor, Premature/*immunology/parasitology/pathology MH - Placenta/metabolism/*pathology MH - Plasmodium berghei/*immunology MH - Pregnancy MH - Xenobiotics/metabolism PMC - PMC6685947 COIS- The authors declare no competing interests. EDAT- 2019/08/09 06:00 MHDA- 2020/10/28 06:00 PMCR- 2019/08/07 CRDT- 2019/08/09 06:00 PHST- 2019/04/12 00:00 [received] PHST- 2019/07/25 00:00 [accepted] PHST- 2019/08/09 06:00 [entrez] PHST- 2019/08/09 06:00 [pubmed] PHST- 2020/10/28 06:00 [medline] PHST- 2019/08/07 00:00 [pmc-release] AID - 10.1038/s41598-019-47865-3 [pii] AID - 47865 [pii] AID - 10.1038/s41598-019-47865-3 [doi] PST - epublish SO - Sci Rep. 2019 Aug 7;9(1):11488. doi: 10.1038/s41598-019-47865-3.