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Title: Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling
Author: Guitart Mampel, Mariona
Juárez Flores, Diana Luz
Youssef, Lina
Morén Núñez, Constanza
Garcia Otero, Laura
Roca Agujetas, Vicente
Catalán García, Marc
González Casacuberta, Ingrid
Tobías Baraja, Ester
Milisenda, José
Grau Junyent, Josep M. (Josep Maria)
Crispi Brillas, Fàtima
Gratacós Solsona, Eduard
Cardellach, Francesc
Garrabou Tornos, Glòria
Keywords: Bioenergètica
Issue Date: 2-Apr-2019
Publisher: John Wiley & Sons
Abstract: 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 mitochondrial 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/β-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.
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It is part of: Journal of Cellular and Molecular Medicine, 2019, vol. 23, num. 6, p. 3962-3973
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ISSN: 1582-1838
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
Articles publicats en revistes (Medicina)

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