Location: Healthy Body Weight ResearchTitle: Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats Author
Submitted to: Journal of Reproductive Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2016
Publication Date: 11/1/2016
Publication URL: http://handle.nal.usda.gov/10113/5852157
Citation: Dekrey, E.E., Roemmich, J.N., Larson, K.J. 2016. Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats. Journal of Reproductive Immunology. 118:9-17.
Interpretive Summary: A maternal low protein diet can reduce offspring birth weight which can lead to rapid weight gain of fat tissue during adolescence and into adulthood and increase the risk for insulin resistance. The placenta functions to provide nutrients for the fetus. Placental function is dependent on regulation of immune cell populations and growth and blood vessel factors. We hypothesize that a maternal low protein diet leads to a dysregulation of immune cell populations, inflammation, and growth factors. Using a rat model, we found that a maternal low protein diet led to a decrease in the weight and efficiency of the placenta. The maternal low protein diet increased immune cell, growth and blood vessel factors of FGF2, VEGFR-1, IGF2, and M2 TNFa+ macrophages. There was a decrease the immune cells, M1 macrophages and iNKT cells, which normally inhibit blood vessel formation. These results indicate that a maternal low protein diet forces the placenta to increase mechanisms of blood vessel formation in order to compensate and fulfill the nutrient demand of the fetus.
Technical Abstract: A maternal low-protein (LP) diet results in low birth weight, increased offspring rapid adipose tissue catch-up growth, adult obesity, and insulin resistance in Sprague-Dawley rats. The placenta functions to fulfill the fetus’ nutrient demands. Placental function is dependent on regulation of immune cell populations and growth and angiogenic factors. Therefore, we hypothesize that a maternal LP diet leads to placental dysfunction through dysregulation of immune cell populations, cytokine production, and growth/angiogenic factors. Obese-prone Sprague-Dawley dams were fed 8% LP or 20% normal protein diets for 3 weeks prior to breeding and through pregnancy. Maternal LP diet led to a decrease in placental weight and efficiency. LP diet placentas had an increase in angiogenic factors, FGF2, VEGFR-1, IGF2, M2 macrophages producing TNFa and a decrease in M1 macrophages and iNKT cells. These results suggest that prenatal protein restriction forces the placenta to upregulate compensating mechanisms of angiogenesis in order to fulfill the nutrient demands of the fetus.