Dietary soy protein supplementation during lactation ameliorates growth and stress-axis dysregulation in low birth weight rats

The Developmental Origins of Health and Disease (DOHaD) hypothesis highlights the pivotal role of early-life nutrition in shaping lifelong health and disease risk. Low birth weight (LBW) remains a major public health issue associated with increased susceptibility to metabolic and cardiovascular disease, underscoring the need for early nutritional interventions. We investigated whether dietary supplementation with soy protein isolate (SPI) during lactation could mitigate adverse developmental programming in a rat model of LBW induced by maternal calorie restriction. Dams received an SPI-supplemented diet during lactation, and offspring were evaluated for postnatal growth, circulating IGF-1 and corticosterone concentrations, and pituitary expression of Gas5 lncRNA, miR-23b, and Pomc. Stress responsiveness and glucocorticoid receptor sensitivity were also assessed. SPI supplementation restored postnatal growth and IGF-1 concentrations in female offspring, and in males, it normalized pituitary Gas5 lncRNA and Pomc mRNA expressions, reduced stress-induced corticosterone hypersecretion, and improved pituitary glucocorticoid sensitivity. These findings indicate that SPI intervention during lactation can partially reverse epigenetic dysregulation of the stress and somatotropic axes caused by fetal undernutrition. Nutritional modulation during lactation thus represents a critical window for early intervention in LBW offspring. SPI supplementation may enhance endocrine and metabolic resilience, providing a practical nutritional programming approach to reduce future disease risk, consistent with the DOHaD paradigm.