Cardiac and placental mitochondrial characterization in a rabbit model of intrauterine growth restriction

Abstract

These findings may allow the design of dietary interventions to modulate Sirtuin3 expression and consequent regulation of mitochondrial imbalance associated with IUGR and derived cardiovascular remodeling.

Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling

“…Overall, these studies pointed out mitochondrial alterations as a potential target in IUGR but also highlighted the need for deep mitochondrial characterisation where Sirtuin3 implication may also be explored. Our group previously evidenced mitochondrial transcriptomic, ultrastructural and function alterations in the target tissue of CVR (heart) and placental insufficiency (placenta) in a rabbit model of IUGR . To validate these findings in human pregnancies, the present work hypothesised that similar mitochondrial disarrangements would be present in human placenta .…”

“…Our group previously evidenced mitochondrial transcriptomic, ultrastructural and function alterations in the target tissue of CVR (heart) and placental insufficiency (placenta) in a rabbit model of IUGR . To validate these findings in human pregnancies, the present work hypothesised that similar mitochondrial disarrangements would be present in human placenta . This information could generate fresh insights in disease aetiology that, in turn, could be useful to develop targeted interventions aimed to reverse this obstetric outcome.…”

“…The molecular basis of IUGR and CVR is still a matter of doubt, but major concerns are raised due to the high prevalence of this obstetric problem and the putative consequences in adulthood. Previous experimental studies pointed out that mitochondrial deficits play a relevant role in IUGR and associated CVR . However, few and contrasting studies were found in the literature investigating mitochondrial alterations in human pregnancies, pointing out the need for a wider study of mitochondrial involvement in patients with this obstetric complication.…”

“…The enzymatic activities of MRC complexes I, II, IV, I + III and II + III (CI, CII, CIV, CI + III and CII + III) were measured spectrophotometrically in placenta according to national standardised methods . Following the same protocols, the measurement of enzymatic activities of MRC in maternal PBMC and neonatal CBMC was restricted to CII and CIV based on previous results of mitochondrial function obtained from the animal model …”

Models of Intrauterine growth restriction and fetal programming in rabbits

“…There were also changes in the heart and kidneys in rabbit kits in response to surgical ligature of uteroplacental vessels. In particular, reduced uteroplacental blood flow decreased fetal heart weight and caused systolic and diastolic dysfunction (Schipke et al, ) in association with an increase in myocardial wall thickness, left ventricular hypovascularisation and hypertrophy, altered expression of metabolic genes, and disorganized cardiomyocyte ultrastructure (reduced sarcomere length and mitochondrial density; Gonzalez‐Tendero et al, ; Guitart‐Mampel et al, ; Gumus et al, ; Schipke et al, ; Torre et al, ). Utero‐placental insufficiency also reduced kidney weight, decreased renal glomeruli number and lead to glomerular capillary congestion and oxidative stress in developing rabbits kits (Bassan et al, ; Figueroa et al, ).…”