PMID- 32779889 OWN - NLM STAT- MEDLINE DCOM- 20210512 LR - 20210512 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 24 IP - 18 DP - 2020 Sep TI - Malaria in pregnancy regulates P-glycoprotein (P-gp/Abcb1a) and ABCA1 efflux transporters in the Mouse Visceral Yolk Sac. PG - 10636-10647 LID - 10.1111/jcmm.15682 [doi] AB - 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 x 10(5) 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)-1beta 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. CI - (c) 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Martinelli, Lilian M AU - Martinelli LM AD - Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. FAU - Fontes, Klaus 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, Mila 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 - Andrade, Cherley 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 - Monteiro, Victoria 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 - Gomes, Hanailly R AU - Gomes HR AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Silva-Filho, Joao 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. FAU - Pinheiro, Ana 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 - Vago, Annamaria R AU - Vago AR AD - Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. FAU - Almeida, Fernanda R C L AU - Almeida FRCL AD - Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. FAU - Bloise, Flavia F AU - Bloise FF AD - Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Matthews, Stephen G AU - Matthews SG AD - Department of Physiology, University of Toronto, Toronto, ON, Canada. AD - Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada. AD - Department of Medicine, University of Toronto, Toronto, ON, Canada. AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. FAU - Ortiga-Carvalho, Tania 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. FAU - Bloise, Enrrico AU - Bloise E AUID- ORCID: 0000-0003-0275-8686 AD - Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. LA - eng GR - OPP1107597/GATES/Bill & Melinda Gates Foundation/United States GR - Foundation-148368/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200811 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (ABCA1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP Binding Cassette Transporter, Subfamily B) RN - 0 (Cytokines) RN - 0 (Membrane Transport Proteins) RN - 0 (RNA, Messenger) RN - 9EI49ZU76O (multidrug resistance protein 3) SB - IM MH - ATP Binding Cassette Transporter 1/*biosynthesis/genetics MH - ATP Binding Cassette Transporter, Subfamily B/*biosynthesis/genetics MH - Animals MH - Biological Transport MH - Cytokines/biosynthesis/genetics MH - Female MH - Fetal Growth Retardation/etiology MH - *Gene Expression Regulation MH - Inflammation MH - Malaria/complications/genetics/*metabolism MH - Membrane Transport Proteins/biosynthesis/genetics MH - Mice MH - Mice, Inbred C57BL MH - Organ Size MH - Plasmodium berghei MH - Pregnancy MH - Pregnancy Complications, Infectious/genetics/*metabolism MH - RNA, Messenger/biosynthesis/genetics MH - Yolk Sac/*metabolism/ultrastructure PMC - PMC7521277 OTO - NOTNLM OT - Plasmodium berghei ANKA OT - ABCA1 OT - ABCG1 OT - Breast Cancer Resistance Protein (BCRP) OT - P-glycoprotein (P-gp) OT - malaria in pregnancy (MiP) OT - yolk sac COIS- The authors confirm that there are no conflicts of interest. EDAT- 2020/08/12 06:00 MHDA- 2021/05/13 06:00 PMCR- 2020/09/01 CRDT- 2020/08/12 06:00 PHST- 2019/12/28 00:00 [received] PHST- 2020/06/09 00:00 [revised] PHST- 2020/07/09 00:00 [accepted] PHST- 2020/08/12 06:00 [pubmed] PHST- 2021/05/13 06:00 [medline] PHST- 2020/08/12 06:00 [entrez] PHST- 2020/09/01 00:00 [pmc-release] AID - JCMM15682 [pii] AID - 10.1111/jcmm.15682 [doi] PST - ppublish SO - J Cell Mol Med. 2020 Sep;24(18):10636-10647. doi: 10.1111/jcmm.15682. Epub 2020 Aug 11.