Postnatal persistence of nonhuman primate sex-dependent renal structural and molecular changes programmed by intrauterine growth restriction.

BACKGROUND: Poor nutrition during fetal development programs postnatal kidney function. Understanding postnatal consequences in nonhuman primates (NHP) is important for translation to our understanding the impact on human kidney function and disease risk. We hypothesized that intrauterine growth restriction (IUGR) in NHP persists postnatally, with potential molecular mechanisms revealed by Western-type diet challenge. METHODS: IUGR juvenile baboons were fed a 7-week Western diet, with kidney biopsies, blood, and urine collected before and after challenge. Transcriptomics and metabolomics were used to analyze biosamples. RESULTS: Pre-challenge IUGR kidney transcriptome and urine metabolome differed from controls. Post-challenge, sex and diet-specific responses in urine metabolite and renal signaling pathways were observed. Dysregulated mTOR signaling persisted postnatally in female pre-challenge. Post-challenge IUGR male response showed uncoordinated signaling suggesting proximal tubule injury. CONCLUSION: Fetal undernutrition impacts juvenile offspring kidneys at the molecular level suggesting early-onset blood pressure dysregulation.

The non-human primate kidney transcriptome in fetal development.

BACKGROUND: Little is known about the repertoire of non-human primate kidney genes expressed throughout development. The present work establishes an understanding of the primate renal transcriptome during fetal development in the context of renal maturation. METHODS: The baboon kidney transcriptome was characterized at 60-day gestation (DG), 90 DG, 125 DG, 140 DG, 160 DG and adulthood (6-12 years) using gene arrays and validated by QRT-PCR. Pathway and cluster analyses were used to characterize gene expression in the context of biological pathways. RESULTS: Pathway analysis indicated activation of pathways not previously reported as relevant to kidney development. Cluster analysis also revealed gene splice variants with discordant expression profiles during development. CONCLUSIONS: This study provides the first detailed genetic analysis of the developing primate kidney, and our findings of discordant expression of gene splice variants suggest that gene arrays likely provide a simplified view and demonstrate the need to study the fetal renal proteome.