Postnatal persistence of sex-dependent renal developmentally programmed structural and molecular changes in nonhuman primates

摘要: Background: Poor nutrition during development programs kidney function. No studies on postnatal consequences of decreased perinatal exist in nonhuman primates (NHP) for translation to human renal disease. Our baboon model moderate maternal nutrient restriction (MNR) produces intrauterine growth restricted (IUGR) and fetal phenotype. We hypothesized that the IUGR phenotype persists postnatally, influencing responses a high-fat, high-carbohydrate, high-salt (HFCS) diet. Methods: Pregnant baboons ate chow (Control; CON) or 70% control intake from 0.16 gestation through lactation. MNR offspring were at birth. At weaning, all (CON females males, n=3/group) chow. ~4.5 years age, blood, urine, biopsies collected before after 7-week HFCS diet challenge. Kidney function, unbiased gene expression, untargeted urine metabolomics evaluated. Results: female male transcriptome metabolome differed CON 3.5 years, prior HFCS. After challenge, we observed sex-specific exposure-specific creatinine, metabolites, signaling pathways. Conclusions: previously showed mTOR dysregulation kidneys. Before HFCS, expression analysis indicated postnatally females. response uncoordinated pathway suggestive proximal tubule injury. To our knowledge, this is first study comparing juvenile NHP impact life caloric mismatch. Perinatal history needs be taken into account when assessing disease risk.