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

摘要: Poor maternal nutrition in pregnancy affects fetal development, predisposing offspring to cardiometabolic diseases. The role of mitochondria during development on later-life cardiac dysfunction caused by nutrient reduction (MNR) remains unexplored. We hypothesized that MNR gestation causes bioenergetic deficits, compromising mitochondrial metabolism and reserve capacity. To enable human translation, we developed a primate baboon model (Papio spp.) moderate which mothers receive 70% control pregnancy, resulting intrauterine growth restriction (IUGR) later exhibiting myocardial remodeling heart failure at equivalent ∼25 years. Term were necropsied following cesarean-section, left ventricle (LV) samples collected. adversely impacted LV sex-dependent fashion. Increased plasma aspartate aminotransferase, creatine phosphokinase (CPK), elevated cortisol levels concomitant with decreased blood insulin male measured. resulted two-fold increase DNA (mtDNA). increased transcripts for several respiratory chain (NDUFB8, UQCRC1, cytochrome c) adenosine triphosphate (ATP) synthase proteins. However, complex I II/III activities significantly decreased, possibly contributing the 73% ATP content lipid peroxidation. showed sparse disarranged cristae dysmorphology. Conclusion: disruption fitness likely contributes documented developmental programming adult dysfunction, indicating programmed inability deliver sufficient energy tissues as chronic mechanism failure.