Omics-based molecular signatures of adrenal, kidney, and lung development in male rat offspring exposed to maternal protein restriction.

BACKGROUND AND AIMS: Maternal malnutrition remains a global social and public health challenge, with long-lasting effects on offspring's health, as proposed by the Developmental Origins of Health and Disease (DOHaD) theory. Here, we investigated the impact of maternal protein restriction (MPR) during gestation and lactation on the global proteomic profiles of the kidneys, lungs, and adrenal glands in post-weaning male rats.

METHODS

Using in silico strategies applied to the proteomic profile, integrating curated databases and complementary statistical approaches, we performed a multiscale biological mapping encompassing macrobiological processes (biological pathways), microbiological levels (cellular, molecular, biochemical, and nuclear features), developmental disease susceptibility, epigenetic regulation, and cell-type-specific localization of shared biomarkers, which were further supported by gene expression validation.

RESULTS

Thirty-six differentially expressed proteins (DEP) were commonly dysregulated across the three organs, enriching pathways related to cellular transport, stress response, chaperone, amino acid metabolism, pyruvate metabolism, the Krebs cycle, and cell cycle regulation (adjusted p-value <0.05). Enrichment analyses indicated alterations in cytoskeletal and nuclear components, with molecular functions involving GTP binding, nucleoside activity, ubiquitination, RNA processing, and redox homeostasis (p < 0.05). Biochemical pathways highlighted disruptions in NAD/NADH balance, energy metabolism, oxygen transport, and purine/pyrimidine metabolism (based on p-value and FDR), with chromosomal enrichment. Interaction networks revealed clusters involving cytoskeletal organization, hemostasis, and energy metabolism, with strong epigenetic associations involving miR-3064-3p/3065-3p (TUBA1A), miR-350/3585-5p (MDH1), and miR-455-3p/92a-1-5p (H2AZ1). These three proteins emerged as potential early-life molecular markers of MPR.

CONCLUSIONS

Overall, this study provides a systems-level overview of MPR effects on adrenal, kidney, and lung development, identifying shared proteomic signatures and candidate biomarkers predictive of developmental impairment and long-term risk for chronic metabolic disease.