Sex-dependent vulnerability of fetal nonhuman primate cardiac mitochondria to moderate maternal nutrient reduction.

Autor:	Pereira SP; CNC-Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3004-504, Portugal.; University of Coimbra, Department of Life Sciences, Coimbra 3000-456, Portugal.; Center for Pregnancy and Newborn Research, University of Texas Health Science Center at San Antonio, San Antonio 78229-3900, TX, U.S.A., Tavares LC; CNC-Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3004-504, Portugal.; University of Coimbra, Department of Life Sciences, Coimbra 3000-456, Portugal., Duarte AI; CNC-Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3004-504, Portugal., Baldeiras I; CNC-Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3004-504, Portugal.; Neurological Clinic, Faculty of Medicine, University of Coimbra, Coimbra 3000-354, Portugal., Cunha-Oliveira T; CNC-Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3004-504, Portugal., Martins JD; CNC-Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3004-504, Portugal., Santos MS; CNC-Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3004-504, Portugal.; University of Coimbra, Department of Life Sciences, Coimbra 3000-456, Portugal., Maloyan A; Center for Pregnancy and Newborn Research, University of Texas Health Science Center at San Antonio, San Antonio 78229-3900, TX, U.S.A., Moreno AJ; University of Coimbra, Department of Life Sciences, Coimbra 3000-456, Portugal., Cox LA; Department of Genetics, Texas Biomedical Research Institute, San Antonio 78245-0549, TX, U.S.A., Li C; Wyoming Pregnancy and Life Course Health Center, University of Wyoming, Laramie 82071-3684, WY, U.S.A., Nathanielsz PW; Wyoming Pregnancy and Life Course Health Center, University of Wyoming, Laramie 82071-3684, WY, U.S.A., Nijland MJ; Center for Pregnancy and Newborn Research, University of Texas Health Science Center at San Antonio, San Antonio 78229-3900, TX, U.S.A., Oliveira PJ; CNC-Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3004-504, Portugal.
Jazyk:	angličtina
Zdroj:	Clinical science (London, England : 1979) [Clin Sci (Lond)] 2021 May 14; Vol. 135 (9), pp. 1103-1126.
DOI:	10.1042/CS20201339
Abstrakt:	Poor 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. (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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