Early-life malnutrition results in structural alterations in the kidney, predisposing offspring to later life renal dysfunction. Kidneys of growth restricted adults at birth have substantial variation in nephron endowment. Animal models indicate renal structural and functional consequences in offspring exposed to suboptimal intrauterine nutrition. Mitochondrial bioenergetics play a key role in renal energy metabolism, growth and function. We hypothesized that moderate maternal nutrient reduction (MNR) would adversely impact fetal renal mitochondrial expression in a well-established non-human primate model which produces intra-uterine growth reduction (IUGR) at term. Female baboons were fed normal chow (C) or 70% of C diet (MNR). Fetal kidneys were harvested at cesarean-section at 0.9 gestation (165 days gestation). Human Mitochondrial Energy Metabolism and the Human Mitochondria Pathway PCR Arrays were used to analyze mitochondrial-relevant mRNA expression. In situ protein content was detected by immunohistochemistry. Despite the smaller overall size, fetal kidney:body weight ratio was not affected. We demonstrated fetal gender-specific differential mRNA expression encoding mitochondrial metabolite transport and dynamics proteins. MNR-related differential gene expression was more evident in female (F), with 16 transcripts significantly altered, including 14 down-regulated and 2 up-regulated. MNR impacted 10 transcripts in male (M) fetuses, with 7 down-regulated and 3 up-regulated. Alteration in mRNA levels was accompanied by a decrease in mitochondrial protein COX6C, a cytochrome c oxidase subunit. In conclusion, transcripts encoding fetal renal mitochondrial energy metabolism proteins are nutrition-sensitive in a gender-dependent manner. We speculate these differences lead to decreased mitochondrial fitness that contributes to renal dysfunction in later life.
- fetal programming
- non-human primate
- Copyright © 2014, American Journal of Physiology - Renal Physiology