Iron overload in Plasmodium berghei-infected placenta as a pathogenesis mechanism of fetal death

Penha-Gonçalves, Carlos; Gozzelino, Raffaella; de Moraes, Luciana V.

Publication

Iron overload in Plasmodium berghei-infected placenta as a pathogenesis mechanism of fetal death

2014-07-01Journal article

dc.contributor.author	Penha-Gonçalves, Carlos
dc.contributor.author	Gozzelino, Raffaella
dc.contributor.author	de Moraes, Luciana V.
dc.date.accessioned	2015-10-06T15:38:19Z
dc.date.available	2015-10-06T15:38:19Z
dc.date.issued	2014-07-01
dc.description	This deposit is composed by the main article, and it hasn't any supplementary materials associated.
dc.description.abstract	Plasmodium infection during gestation may lead to severe clinical manifestations including abortion, stillbirth, intrauterine growth retardation, and low birth weight. Mechanisms underlying such poor pregnancy outcomes are still unclear. In the animal model of severe placental malaria (PM), in utero fetal death frequently occurs and mothers often succumb to infection before or immediately after delivery. Plasmodium berghei-infected erythrocytes (IEs) continuously accumulate in the placenta, where they are then phagocytosed by fetal-derived placental cells, namely trophoblasts. Inside the phagosomes, disruption of IEs leads to the release of non-hemoglobin bound heme, which is subsequently catabolized by heme oxygenase-1 into carbon monoxide, biliverdin, and labile iron. Fine-tuned regulatory mechanisms operate to maintain iron homeostasis, preventing the deleterious effect of iron-induced oxidative stress. Our preliminary results demonstrate that iron overload in trophoblasts of P. berghei-infected placenta is associated with fetal death. Placentas which supported normally developing embryos showed no iron accumulation within the trophoblasts. Placentas from dead fetuses showed massive iron accumulation, which was associated with parasitic burden. Here we present preliminary data suggesting that disruption of iron homeostasis in trophoblasts during the course of PM is a consequence of heme accumulation after intense IE engulfment. We propose that iron overload in placenta is a pathogenic component of PM, contributing to fetal death. The mechanism through which it operates still needs to be elucidated.	pt_PT
dc.description.sponsorship	FCT: Portugal (EXPL-IMI-IMU-0428/2013), SFRH/BPD/44256/2008, SFRH/BPD/44486/2008.	pt_PT
dc.identifier	10.3389/fphar.2014.00155
dc.identifier.citation	Penha-Gonçalves C, Gozzelino R and de Moraes LV (2014) Iron overload in Plasmodium berghei-infected placenta as a pathogenesis mechanism of fetal death. Front. Pharmacol. 5:155. doi: 10.3389/fphar.2014.00155	pt_PT
dc.identifier.doi	10.3389/fphar.2014.00155
dc.identifier.doi	10.3389/fphar.2014.00155
dc.identifier.uri	http://hdl.handle.net/10400.7/369
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Frontiers Research Foundation	pt_PT
dc.relation.publisherversion	http://journal.frontiersin.org/article/10.3389/fphar.2014.00155/abstract	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	pregnancy malaria	pt_PT
dc.subject	heme	pt_PT
dc.subject	iron	pt_PT
dc.subject	fetal death	pt_PT
dc.subject	trophoblast	pt_PT
dc.title	Iron overload in Plasmodium berghei-infected placenta as a pathogenesis mechanism of fetal death	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.endPage	13	pt_PT
oaire.citation.startPage	1	pt_PT
oaire.citation.title	Frontiers in Pharmacology	pt_PT
oaire.citation.volume	5	pt_PT
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT