Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFα expression in Sprague-Dawley rats

Abstract

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.

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

“…On the other hand, invariant NKT cells, which can inhibit tumor angiogenesis via IFNγ, were significantly reduced in low when compared to normal protein diet placentas, with lower mRNA expression in IFNγ expression, indicating the occurrence of angiogenesis in low protein diet placenta, as evidenced by the greater density of CD31/PECAM (platelet endothelial cell adhesion molecule). Although maternal low protein diet could lead to angiogenesis, the compensatory angiogenesis did not contribute to the nutrition supply, but the opposite, placental dysfunction that is caused by inappropriate polarization may lead to fetal growth retardation and other negative effects aforementioned [50]. …”

Fetal programming of neuropsychiatric disorders

“…Certain nutrients play a major role in regulating development of normal cognition during intrauterine life (Kretchmer et al, ). Maternal low protein intake seems to be at the basis of the insurgence of a pro‐inflammatory environment, leading to inhibition of placental tissue growth and neonatal low birth weight (Vomhof‐Dekrey et al, ). Maternal diet low in choline, an essential nutrient, increases the risk of neural tube defects in the developing fetal brain, leading to low performance on cognitive tests in children (Fig.…”

Lipidomic Analysis of TRPC1 Ca2+-Permeable Channel-Knock Out Mouse Demonstrates a Vital Role in Placental Tissue Sphingolipid and Triacylglycerol Homeostasis Under Maternal High-Fat Diet

“…The neutral lipid products quantified above implicate several enzymatic pathways for CE, TAG and fatty acid synthesis which could be addressed using transcriptomic analysis ( 46 ). Placental inflammation and vascular development could be assessed as we have in prior work ( 47 ). Limitations in sample availability preclude following up on these lines of inquiry for this study.…”