Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/95125
DC FieldValueLanguage
dc.contributor.authorPereira, Susana P-
dc.contributor.authorTavares, Ludgero C-
dc.contributor.authorDuarte, Ana I.-
dc.contributor.authorBaldeiras, Inês-
dc.contributor.authorCunha-Oliveira, Teresa-
dc.contributor.authorMartins, João D-
dc.contributor.authorSantos, Maria S-
dc.contributor.authorMaloyan, Alina-
dc.contributor.authorMoreno, Antonio J.-
dc.contributor.authorCox, Laura A-
dc.contributor.authorLi, Cun-
dc.contributor.authorNathanielsz, Peter W-
dc.contributor.authorNijland, Mark J-
dc.contributor.authorOliveira, Paulo J.-
dc.date.accessioned2021-06-30T13:51:02Z-
dc.date.available2021-06-30T13:51:02Z-
dc.date.issued2021-05-14-
dc.identifier.issn0143-5221pt
dc.identifier.issn1470-8736pt
dc.identifier.urihttp://hdl.handle.net/10316/95125-
dc.description.abstractPoor maternal nutrition in pregnancy affects fetal development, predisposing offspring to cardiometabolic diseases. The role of mitochondria during fetal development on later-life cardiac dysfunction caused by maternal nutrient reduction (MNR) remains unexplored. We hypothesized that MNR during gestation causes fetal cardiac bioenergetic deficits, compromising cardiac mitochondrial metabolism and reserve capacity. To enable human translation, we developed a primate baboon model (Papio spp.) of moderate MNR in which mothers receive 70% of control nutrition during pregnancy, resulting in intrauterine growth restriction (IUGR) offspring and later exhibiting myocardial remodeling and heart failure at human equivalent ∼25 years. Term control and MNR baboon offspring were necropsied following cesarean-section, and left ventricle (LV) samples were collected. MNR adversely impacted fetal cardiac LV mitochondria in a sex-dependent fashion. Increased maternal plasma aspartate aminotransferase, creatine phosphokinase (CPK), and elevated cortisol levels in MNR concomitant with decreased blood insulin in male fetal MNR were measured. MNR resulted in a two-fold increase in fetal LV mitochondrial DNA (mtDNA). MNR resulted in increased transcripts for several respiratory chain (NDUFB8, UQCRC1, and cytochrome c) and adenosine triphosphate (ATP) synthase proteins. However, MNR fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, possibly contributing to the 73% decreased ATP content and increased lipid peroxidation. MNR fetal LV showed mitochondria with sparse and disarranged cristae dysmorphology. Conclusion: MNR disruption of fetal cardiac mitochondrial fitness likely contributes to the documented developmental programming of adult cardiac dysfunction, indicating a programmed mitochondrial inability to deliver sufficient energy to cardiac tissues as a chronic mechanism for later-life heart failure.pt
dc.language.isoengpt
dc.publisherPortland Presspt
dc.rightsembargoedAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectCardiac metabolic flexibilitypt
dc.subjectCardiometabolic diseasept
dc.subjectHeartpt
dc.subjectMaternal nutrition & fetal developmentpt
dc.subjectSexual dimorphismpt
dc.titleSex-dependent vulnerability of fetal nonhuman primate cardiac mitochondria to moderate maternal nutrient reductionpt
dc.typearticle-
degois.publication.firstPage1103pt
degois.publication.lastPage1126pt
degois.publication.issue9pt
degois.publication.titleClinical Sciencept
dc.relation.publisherversionhttps://portlandpress.com/clinsci/article-abstract/135/9/1103/228457/Sex-dependent-vulnerability-of-fetal-nonhumanpt
dc.peerreviewedyespt
dc.identifier.doi10.1042/CS20201339pt
degois.publication.volume135pt
dc.date.embargo2022-05-14*
uc.date.periodoEmbargo365pt
item.fulltextCom Texto completo-
item.grantfulltextembargo_20220514-
item.languageiso639-1en-
crisitem.author.deptCNC - Center for Neuroscience and Cell Biology-
crisitem.author.deptInstitute of Interdisciplinary Research-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-1168-2444-
crisitem.author.orcid0000-0002-8106-7308-
crisitem.author.orcid0000-0002-7382-0339-
crisitem.author.orcid0000-0002-5201-9948-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
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This item is licensed under a Creative Commons License Creative Commons