Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFα expression in Sprague-Dawley rats.
A maternal low-protein (LP) diet in Sprague-Dawley rats results in low birth weight, rapid adipose tissue catch-up growth, adult obesity, and insulin resistance. The placenta functions to fulfill the fetus' nutrient demands. Adequate angiogenic factor concentrations help to ensure normal growth and vasculature development of the placenta and, in turn, optimum maternal-to-fetal nutrient delivery. Maternal malnutrition creates a proinflammatory environment that leads to inhibition of placental tissue growth. Therefore, we hypothesized that a maternal LP diet will lead to abnormal angiogenesis via dysregulation of immune cells resulting in increased secretion of proinflammatory cytokines and reduced angiogenic factor expression. Sprague-Dawley dams were fed 8% LP or 20% normal protein diets for 3 weeks prior to breeding and throughout pregnancy. Placenta from dams fed a LP diet weighed less; had increased M2 macrophages producing TNFα, decreased M1 macrophages and iNKT cells; greater angiogenic factor (FGF2, VEGFR-1, IGF2) expression and protein content, and greater CD31/PECAM (platelet endothelial cell adhesion molecule) expression. Prenatal protein restriction may induce the placenta to upregulate compensatory mechanisms of angiogenesis in order to meet the nutrient demands of the fetus.
USDA -ARS, Human Nutrition Research Center, Grand Forks, ND 58203, United States; University of North Dakota, School of Medicine and Health Sciences, Department of Surgery, Grand Forks, ND 58202, United States.
Emilie
E
Vomhof-DeKrey
University of North Dakota, School of Medicine and Health Sciences, Department of Biology, Grand Forks, ND 58202, United States.
Diane
D
Darland
University of North Dakota, School of Medicine and Health Sciences, Department of Basic Sciences, Grand Forks, ND 58202, United States.
Othman
O
Ghribi
USDA -ARS, Human Nutrition Research Center, Grand Forks, ND 58203, United States.
Amy
A
Bundy
USDA -ARS, Human Nutrition Research Center, Grand Forks, ND 58203, United States.
James
J
Roemmich
USDA -ARS, Human Nutrition Research Center, Grand Forks, ND 58203, United States. Electronic address: kate.claycombe@ars.usda.gov.
Kate
K
Claycombe
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018753:Diet, Protein-Restricted; D005260:Female; D008264:Macrophages / Q000502:physiology*; D044342:Malnutrition / Q000276:immunology*; D018811:Maternal Exposure / Q000009:adverse effects; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000276:immunology*; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha
Angiogenesis; Fibroblast growth factor; Low protein diet; M1 and M2 macrophages; iNKT cells