Long-term effects of maternal protein restriction on adrenal proteomic profile and steroidogenesis in male offspring rats

Abstract

Maternal protein restriction (MPR) can significantly affect offspring's early development and aging, impacting several organs, including the adrenal glands. This study evaluated the adrenal proteomic profile in male rat offspring exposed to MPR during pregnancy and lactation. Male offspring were divided into two groups: Control (CTR), born to dams fed a normoprotein diet (17 % protein), and Gestational and Lactational Low-Protein (GLLP), born to dams fed a low-protein diet (6 % protein) throughout gestation and lactation, and after received control diet. Offspring were euthanized at postnatal day (PND) 21 or PND 540. Blood samples and adrenal glands were processed for histological, metabolic, molecular, and proteomic assessments. At PND21, the GLLP group exhibited reduced adrenal gland mass and cortical thickness. At PND21, the proteomic landscape showed that the most impacted biological pathways were associated with decreased steroid hormone synthesis, increased glucose metabolism, and stress response. At PND540, the main impacts were increased apoptotic pathway, stress response, and steroid hormone synthesis, with decreased glucose metabolism. At PND 540, the GLLP group showed higher adrenal collagen content and elevated apoptosis. Age-related changes included decreased peroxiredoxin 3 and increased expression of aldosterone synthase (Cyp11b2). Furthermore, steroid 11-Beta-Hydroxylase (Cyp11b1) expression decreased at PND540, alongside reduced serum aldosterone and elevated serum corticosterone levels. These results suggest that MPR modulates the adrenal glands' proteomic profile, serving as a pivotal mechanism underpinning diverse systemic diseases. It influences adrenal morphophysiology early in life, with long-lasting consequences for cellular stress, immune response, and catabolic pathways in male offspring with aging.