Assessment of prenatal cerebral and cardiac metabolic changes in a rabbit model of fetal growth restriction based on ¹³ C-labelled substrate infusions and ex vivo multinuclear HRMAS

© 2018 Simões et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background We have used a previously reported rabbit model of fetal growth restriction (FGR), reproducing perinatal neurodevelopmental and cardiovascular impairments, to investigate the main relative changes in cerebral and cardiac metabolism of term FGR fetuses during nutrient infusion. Methods FGR was induced in 9 pregnant New Zealand rabbits at 25 days of gestation: one horn used as FGR, by partial ligation of uteroplacental vessels, and the contralateral as control (appropriate for gestation age, AGA). At 30 days of gestation, fasted mothers under anesthesia were infused i.v. with 1- 13 C-glucose (4 mothers), 2- 13 C-acetate (3 mothers), or not infused (2 mothers). Fetal brain and heart samples were quickly harvested and frozen down. Brain cortex and heart apex regions from 30 fetuses were studied ex vivo by HRMAS at 4C, acquiring multinuclear 1D and 2D spectra. The data were processed, quantified by peak deconvolution or integration, and normalized to sample weight. Results Most of the total 13 C-labeling reaching the fetal brains/hearts (80–90%) was incorporated to alanine and lactate (cytosol), and to the glutamine-glutamate pool (mitochondria). Acetate-derived lactate (Lac C2C3) had a slower turnover in FGR brains (~ -20%). In FGR hearts, mitochondrial turnover of acetate-derived glutamine (Gln C4) was slower (-23%) and there was a stronger accumulation of phospholipid breakdown products.