Assistant Professor University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma, United States
Background: Selenium (Se) plays a central role in the proper functioning of multiple systems, including immunity, inflammation, redox regulation, and antioxidant defense. Healthy infants accrete Se through the placenta during the 3rd trimester of pregnancy and are born with sufficient Se levels, whereas, preterm are born Se deficient. Recently, increased oxidative stress and decreased Gpx4, antioxidant selenoprotein, were reported in necrotizing enterocolitis, (NEC). Mechanisms by which maternal Se contributes to neonatal gut development and endogenous antioxidant responses are unknown. Objective: The presents studies were designed to test the hypothesis that maternal Se deficiency will attenuate offspring antioxidant capacities and increase baseline intestinal inflammation, resulting in disrupted intestinal growth. Design/Methods: C3H/HeN mice were fed Se-sufficient (SeS; 0.4 ppm Na2SeO3) or Se-deficient (SeD; < 0.01 ppm Na2SeO3) diets from weaning, and subsequently bred to create SeS and SeD litters. SeS and SeD pups were nursed by dams of corresponding diets from birth through Day 14. Upon sacrifice, small intestines were collected, measured for length, H&E stained, snap frozen for protein analysis and preserved with RNA later. Data (mean±SD) were analyzed by students t-test (p < 0.05). Results: Murine models of Se deficiency have demonstrated stunted growth throughout development, and our preliminary data support this finding with a 20% (p < 0.0001) reduction in body weight at Day 14. However, examining intestinal length corrected for body weight, the SeD pups have increased intestinal length (2.746±0.089 vs 2.232±0.180 cm/g). Ki67 protein expression, a marker of cell proliferation, supported these observations; SeD pups showed increased expression, normalized to β-actin (0.752±0.02 vs 0.585±0.068; p< 0.0015). SeD pups exhibited decrease GPX, antioxidant protein expression, normalized to β-actin compared to SeS controls; Gpx1 (0.0±0 vs 1.235±0.239; p< 0.0001) and GpX4 (0.0±0 vs 0.797±0.356; p< 0.001), leading to potential oxidative stress and injury. Preliminary cytokine expression levels show dysregulation (IL1β and IL6 decrease in SeD pups). Confirmatory experiments are ongoing.
Conclusion(s): Our findings suggest a critical role for Se in modulating perinatal intestinal development. Gpx1 & 4 decreases suggest an increased risk for oxidative stress, and potential risk of tissue injury. Given the prevalence of Se deficiency in preterm infants, further investigation into the contribution of the morphological changes and aberrant antioxidant response in the gut prior to and during NEC is essential.
