Effects of moderate global maternal nutrient reduction on fetal baboon renal mitochondrial gene expression at 0.9 gestation

Abstract

Pereira SP, Oliveira PJ, Tavares LC, Moreno AJ, Cox LA, Nathanielsz PW, Nijland MJ. Effects of moderate global maternal nutrient reduction on fetal baboon renal mitochondrial gene expression at 0.9 gestation. Am J Physiol Renal Physiol 308: F1217-F1228, 2015. First published March 11, 2015 doi:10.1152/ajprenal.00419.2014.-Early life malnutrition results in structural alterations in the kidney, predisposing offspring to later life renal dysfunction. Kidneys of adults who were growth restricted at birth have substantial variations in nephron endowment. Animal models have indicated 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 nonhuman primate model that produces intrauterine growth reduction at term. Female baboons were fed normal chow diet or 70% of control diet (MNR). Fetal kidneys were harvested at cesarean section at 0.9 gestation (165 days gestation). Human Mitochondrial Energy Metabolism and Human Mitochondria Pathway PCR Arrays were used to analyze mitochondrially relevant mRNA expression. In situ protein content was detected by immunohistochemistry. Despite the smaller overall size, the fetal kidney weight-to-body weight ratio was not affected. We demonstrated fetal sex-specific differential mRNA expression encoding mitochondrial metabolite transport and dynamics proteins. MNRrelated differential gene expression was more evident in female fetuses, with 16 transcripts significantly altered, including 14 downregulated and 2 upregulated transcripts. MNR impacted 10 transcripts in male fetuses, with 7 downregulated and 3 upregulated transcripts. The alteration in mRNA levels was accompanied by a decrease in mitochondrial protein cytochrome c oxidase subunit VIc. In conclusion, transcripts encoding fetal renal mitochondrial energy metabolism proteins are nutrition sensitive in a sex-dependent manner. We speculate that these differences lead to decreased mitochondrial fitness that contributes to renal dysfunction in later life. mitochondria; kidney; fetal programming; nonhuman primate; gene expression SUBOPTIMAL PRENATAL DEVELOPMENT predisposes to adult onset diseases such as hypertension, diabetes, cardiovascular, and renal disease (2,9,42,64). Importantly, there is clear evidence that the developing nonhuman primate kidney is sensitive to decreased maternal nutrition (45). Poor intrauterine nutrition is associated with reduced nephron number in both animals and humans (29,35,41,62). Analysis of renal autopsies of adults born with low birth weight has shown substantial variations in renal composition (26). Remarkably, little attention has been given to the possible involvement of mitochondria as putative mediators between maternal nutrient reduction (MNR) and altered renal development in their offspring. This is surpr...

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

“…Sex-dependent changes in renal mitochondrial function were observed in the baboon model of maternal undernutrition [16]. Using a swine model of maternal undernutrition, Gonzalez-Bulnes et al [92] showed that female conceptuses had higher viability rates and lower incidence of severe growth retardation.…”

“…Maternal low protein diet results in high blood pressure in offspring [10], altered endocrine function [9], immune function [7], and renal development [11]. Same long-term consequences of maternal malnutrition were observed in long-gestation, precocial species including r, sheep [12, 13] and nonhuman primates [14-16]. The pig is currently considered a reliable large animal model for translational research in IUGR as result of deficiencies in maternal nutritional supply or placental development [17].…”

Effect of moderate, 30 percent global maternal nutrient reduction on fetal and postnatal baboon phenotype

“…We have demonstrated that this moderate degree of MNR leads to intrauterine growth restriction (IUGR) at term . We have also reported altered development of the placenta, fetal kidney, fetal brain, fetal liver, fetal skeletal muscle, and fetal heart . In postnatal life, these IUGR offspring show cognitive and behavioral changes, accelerated aging of the heart, and a pre‐diabetic metabolic phenotype when compared to controls.…”

Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation

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