Unraveling the Persistent Renal Impact of Intrauterine Growth Restriction and Catch-Up Growth: Integrating Morphological Insights with Metabolomic Profiling

Abstract

The study aimed to investigate the long-term effects of IUGR and consequent catch-up growth on metabolic health by using a comprehensive approach that included histopathological, immunohistochemical, biochemical, and metabolomics analyses. Sprague-Dawley pregnant rats either undergo bilateral uterine artery ligation or a sham surgery on the 19th day of gestation. The offspring reached catch-up growth, kidney samples were collected at postnatal weeks 2, 4, and 8 for analysis. IUGR rats exhibited a spectrum of changes including reduced glomeruli number, proliferating cell number, altered oxidative stress markers, various enzymes involved in Krebs cycle, mitochondrial dynamics, and energy metabolism. Examination of the 8-week-old cohort identified a broader spectrum of metabolic alterations, notably in the biosynthesis of phenylalanine, tyrosine, and tryptophan, phenylalanine, tyrosine, glyoxylate, dicarboxylate, pyruvate, alanine, aspartate, and glutamate metabolism, glycolysis/gluconeogenesis and citrate (TCA) cycle. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, hypertriglyceridemia, cardiovascular diseases, and mental retardation. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies to mitigate the risk of metabolic diseases in individuals with a history of IUGR.