Journal Article Ahead of print 1 citation
PubMed: 42402324 DOI: 10.1016/j.yexcr.2026.115122
Early-Life Cardiovascular Programming by Maternal Protein Restriction: Electrophysiological, Structural, and Molecular Alterations in Female Rats.
Exp Cell Res
Authors: Luísa C Gomes, Matheus N Fioretto, Lucas S Lemos, Luísa A Barata, Flávia A Maciel, Isabelle T Ribeiro, Ana Luiza S de Abreu, Luiz Marcos F Portela, Isabella L Bravo, Erick G Stoppa, Raffael Greggio Willmann, Maycon Tavares E Silva, Clélia Akiko H Lima, José Ricardo de A Miranda, Wellerson Rodrigo Scarano, Luis A Justulin
Affiliations
- Department of Cellular and Molecular Biology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
- Department of Cellular and Molecular Biology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
- Department of Physiology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
- Department of Cellular and Molecular Biology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil; Brazilian National Institute of Science and Technology in DOHaD.
Abstract
Maternal malnutrition is a major risk factor for adverse health outcomes in offspring, including cardiovascular disorders. According to the Developmental Origins of Health and Disease (DOHaD) concept, adverse conditions during critical developmental windows can induce long-lasting physiological adaptations that increase disease susceptibility later in life. Among the experimental models used to investigate these mechanisms, maternal protein restriction (MPR) has been associated with metabolic, cardiovascular, and hypertensive phenotypes in offspring, some of which emerge early in life. Therefore, this study evaluated the effects of MPR on the cardiovascular morphophysiology of female offspring at postnatal day 21 (PND21). Pregnant rats were allocated to either a Control group (CTR), receiving a normoprotein diet (17% protein), or a Gestational and Lactational Low-Protein group (GLLP), receiving a low-protein diet (6% protein) throughout gestation and lactation. At PND21, female offspring underwent electrocardiographic assessment and were subsequently euthanized for morphological, molecular, and oxidative stress analyses. Female offspring from the GLLP group exhibited reduced body weight and body length, whereas absolute heart weight was preserved, resulting in increased relative heart weight and suggesting disproportionate somatic growth. Electrocardiographic analysis revealed a shortened P-R interval and decreased heart rate, indicating early alterations in cardiac electrical activity. Morphologically, cardiomyocyte architecture was preserved; however, reduced nuclear width and increased collagen and elastin deposition were observed, indicating early extracellular matrix remodeling without significant changes in reticular fibers. At the molecular level, GLLP offspring exhibited reduced PRDX3 expression, accompanied by decreased catalase (CAT) activity, reduced glutathione (GSH) levels, and lower lipid peroxidation (TBARS), suggesting alterations in redox regulation and antioxidant homeostasis during early cardiac development. Collectively, these findings demonstrate that MPR induces early structural, molecular, oxidative, and electrophysiological alterations in the hearts of female offspring. These adaptations may represent early programming events that increase susceptibility to cardiovascular dysfunction later in life, reinforcing the importance of maternal nutrition in shaping cardiovascular health across generations.
MeSH
Heart, Diet, Cell Biology