Maternal lipid and cholesterol-enriched diet disrupts fetal development and placental function in a rabbit model
2013
Tarrade, Anne | Aubrière, Marie-Christine | Morel, Olivier | Charpentier, Nicole | Dahirel, Michele | Bertrand-Michel, J. | Chavatte Palmer, Pascale
We have shown that maternal administration of a lipid (8%) and cholesterol (0.2%)-enriched diet (HH diet) in a rabbit model leads to intrauterine growth factor (IUGR) and increased offspring susceptibility to excess body fat, overweight and hypertension in adults.1 To examine the link between the fetal development and metabolic consequences in later life, placental development has been explored. Female rabbits were fed with a control (C) or HH diet from 10 weeks of age and throughout gestation. At 28 days of gestation, dams were anesthetized and a laparotomy was performed to collect placenta and plasma. Fetal weight in HH group was significantly reduced compared with C. Total cholesterol and triglycerides concentrations in HH fetuses were significantly increased by 1.2- and 2.3-fold, respectively, compared with C. The structural analysis of HH placentas revealed an abnormal accumulation of light vesicles, identified as lipid droplets in the trophoblast layer. Total content of cholesterol esters and triglycerides were also significantly increased in HH placentas. The expression of genes involved in placental growth, vascularization and nutrient transfer has been studied. HH placentas were characterized by a significant decrease in LDL- receptor, CD36, LXR-a, ABC-G1, SLC38A1 and SLC38A2 transcripts. The downregulation of LXR-a mRNA was correlated with a decrease in protein expression. These data demonstrate that maternal HH diet reduced cholesterol transport through the placenta as evidenced by placental gene expression and cholesterol ester accumulation. In contrast, fatty acid transport was not regulated, which could explain the excess of body fat in adults.
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