Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/47558
Title: Effects of moderate global maternal nutrient reduction on fetal baboon renal mitochondrial gene expression at 0.9 gestation
Authors: Pereira, Susana P
Oliveira, Paulo J
Tavares, Ludgero C
Moreno, António J
Cox, Laura A
Nathanielsz, Peter W
Nijland, Mark J
Keywords: Animals
Female
Genes, Mitochondrial
Kidney
Maternal Nutritional Physiological Phenomena
Mitochondria
Models, Animal
Papio
Pregnancy
RNA, Messenger
Gene Expression Regulation, Developmental
Gestational Age
Issue Date: 1-Jun-2015
Abstract: 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. MNR-related 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.
Peer review: yes
URI: http://hdl.handle.net/10316/47558
DOI: 10.1152/ajprenal.00419.2014
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais



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