Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 6, Pages 3962-3973Publisher
WILEY
DOI: 10.1111/jcmm.14282
Keywords
bioenergetics; foetal growth; mitochondria; Sirt 3
Categories
Funding
- CIBERER (an initiative of ISCIII)
- Fundacio la Marato de TV3 [87/C/2015]
- Erasmus + Programme of the European Union [20130040]
- Fondo de Investigacion Sanitaria [FIS PI11/01199, PI14/00226, PI15/00817, PI15/00903, PI15/00130, INT16/00168]
- CIBERER
- InterCIBER [PIE1400061]
- Instituto de Salud Carlos III
- Suports a Grups de Recerca and CERCA Programme [SGR893/2017, SGR928/2017]
- CONACyt
- laCaixa Foundation
- Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK)
- Fundacio Privada Cellex [CP042187]
Ask authors/readers for more resources
Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single-site, cross-sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I-stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondria) DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI-stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/beta-actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI-stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new-borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available