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Embryo-fetal and early-life protein restriction programs pulmonary structure and molecular parameters in both dams
Flávia Alessandra Maciel1, Matheus Naia Fioretto1, Luisa Annibal Barata1
1Department of Cellular and Molecular Biology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
Insights
Maternal protein restriction negatively impacts lung health in both mothers and female offspring. This nutritional adversity during development may link to later respiratory diseases.
Area of Science:
- * Developmental biology
- * Respiratory medicine
- * Nutritional science
Background:
- * The Developmental Origins of Health and Disease (DOHaD) theory links early-life conditions to adult disease susceptibility.
- * Maternal protein restriction (MPR) is known to impair offspring lung development.
- * Effects of MPR on maternal lung health and female offspring remain understudied.
Purpose of the Study:
- * To investigate the impact of MPR on lung structure and metabolism in dams and female offspring.
- * To identify potential mechanisms linking nutritional adversity to respiratory disease.
Main Methods:
- * Sprague Dawley rats were fed control or low-protein diets during gestation and lactation.
- * Pulmonary tissues from dams and female offspring were analyzed using histological, biochemical, molecular, zymographic, and in silico methods.
- * Assessments included collagen, mast cells, gene expression, enzyme activity, and lipid peroxidation.
Main Results:
- * MPR induced collagen deposition and mast cell increases in maternal lungs, with reduced reticular fibers.
- * Female offspring showed reduced alveolar diameter, mast cell density, and reticular fibers.
- * MPR altered gene expression related to smooth muscle and energy metabolism in offspring lungs, with increased MMP-2 activity.
Conclusions:
- * MPR adversely affects maternal lung structure, potentially impacting ventilatory function.
- * MPR leads to delayed lung development, ECM remodeling, and metabolic disturbances in female offspring.
- * Findings highlight MPR as a risk factor for respiratory issues, supporting the DOHaD theory.
Abstract:
The Developmental Origins of Health and Disease (DOHaD) theory proposes that adverse conditions during critical developmental windows can increase disease susceptibility throughout life. Maternal protein restriction (MPR) is a well-established experimental model that impairs offspring lung development, affecting pulmonary structure, metabolism, and molecular pathways from early life to aging. However, little is known about its effects on maternal pulmonary health and female offspring, representing an important gap in the literature. Therefore, this study investigated the effects of MPR on lung structure and metabolism in dams at the end of lactation and in female offspring at weaning. Sprague Dawley rats were fed either a control diet (17% protein) or a low-protein diet (6% protein) throughout gestation and lactation. Dams and female offspring were euthanized at weaning, and pulmonary alterations were assessed through histological, biochemical, molecular, zymographic, and in silico analyses. MPR increased collagen deposition, mast cell density, and Acta expression, while reducing reticular fibers in maternal lungs, accompanied by a trend toward increased lipid peroxidation. In female offspring, MPR reduced alveolar diameter, mast cell density, and reticular fibers, while increasing collagen deposition, MMP-2 activity, PI3K and MyoD expression, and decreasing mTOR expression as well as Nduf transcript levels. No significant alterations in antioxidant parameters were observed in either dams or offspring. Integrative analyses indicate that MPR promotes structural remodeling in maternal lungs, potentially compromising ventilatory function. In female offspring, MPR induces delayed pulmonary development, extracellular matrix remodeling, alterations in smooth muscle-related pathways, and disturbances in energy metabolism. Together, these findings demonstrate that maternal protein resQ1triction adversely affects pulmonary health in both dams and female offspring, revealing potential mechanisms linking early-life nutritional adversity to the developmental origins of respiratory disease.
