Malaria in pregnancy regulates P‐glycoprotein (P‐gp/ Abcb1a ) and ABCA1 efflux transporters in the Mouse Visceral Yolk Sac

Martinelli, L. M. et al. (2020) Malaria in pregnancy regulates P‐glycoprotein (P‐gp/ Abcb1a ) and ABCA1 efflux transporters in the Mouse Visceral Yolk Sac. Journal of Cellular and Molecular Medicine, 24(18), pp. 10636-10647. (doi: 10.1111/jcmm.15682) (PMID:32779889) (PMCID:PMC7521277)

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Abstract

Malaria in pregnancy (MiP) induces intrauterine growth restriction (IUGR) and preterm labour (PTL). However, its effects on yolk sac morphology and function are largely unexplored. We hypothesized that MiP modifies yolk sac morphology and efflux transport potential by modulating ABC efflux transporters. C57BL/6 mice injected with Plasmodium berghei ANKA (5 × 105 infected erythrocytes) at gestational day (GD) 13.5 were subjected to yolk sac membrane harvesting at GD 18.5 for histology, qPCR and immunohistochemistry. MiP did not alter the volumetric proportion of the yolk sac's histological components. However, it increased levels of Abcb1a mRNA (encoding P-glycoprotein) and macrophage migration inhibitory factor (Mif chemokine), while decreasing Abcg1 (P < 0.05); without altering Abca1, Abcb1b, Abcg2, Snat1, Snat2, interleukin (Il)-1β and C-C Motif chemokine ligand 2 (Ccl2). Transcripts of Il-6, chemokine (C-X-C motif) ligand 1 (Cxcl1), Glut1 and Snat4 were not detectible. ABCA1, ABCG1, breast cancer resistance protein (BCRP) and P-gp were primarily immunolocalized to the cell membranes and cytoplasm of endodermic epithelium but also in the mesothelium and in the endothelium of mesodermic blood vessels. Intensity of P-gp labelling was stronger in both endodermic epithelium and mesothelium, whereas ABCA1 labelling increased in the endothelium of the mesodermic blood vessels. The presence of ABC transporters in the yolk sac wall suggests that this fetal membrane acts as an important protective gestational barrier. Changes in ABCA1 and P-gp in MiP may alter the biodistribution of toxic substances, xenobiotics, nutrients and immunological factors within the fetal compartment and participate in the pathogenesis of malaria-induced IUGR and PTL.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Da Silva Filho, Dr Joao
Creator Roles:
Authors: Martinelli, L. M., Fontes, K. N., Reginatto, M. W., Andrade, C. B. V., Monteiro, V. R. S., Gomes, H. R., Silva‐Filho, J. L., Pinheiro, A. A. S., Vago, A. R., Almeida, F. R. C. L., Bloise, F. F., Matthews, S. G., Ortiga‐Carvalho, T. M., and Bloise, E.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Cellular and Molecular Medicine
Publisher:Wiley
ISSN:1582-1838
ISSN (Online):1582-4934
Published Online:11 August 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Journal of Cellular and Molecular Medicine 24(18): 10636-10647
Publisher Policy:Reproduced under a Creative Commons License

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