Epigenetic disruption of placental genes by chronic maternal cafeteria diet in rats

Abstract

Maternal diet has impact on reproduction, fetal development and offspring behavior, although molecular mechanisms remained unknown. Our aims were to assess (1) the effects of a cafeteria (CAF) diet (western diet habits) on female reproductive performance, fetal and placental parameters on gestational day 21 and litter size and pup weight at birth; and (2) placental messenger RNA (mRNA) expression and epigenetic regulation of Insulin-Like Growth Factor (Igf) and Vascular Endothelial Growth Factor (Vegf) and their receptors. Female Wistar rats were fed with control or CAF diet from weaning until parturition. At week 14 after diets started, females were mated and half of the animals were euthanized on gestational day 21 to evaluate reproductive parameters including the pregnancy rate, number of corpora lutea, implantation sites and resorption sites. Moreover, fetal weight and length, placental weight, and placental index were recorded. Placentas were collected for mRNA quantification and DNA methylation analysis. The remaining animals were allowed to give birth and the number and weight of the pups were evaluated. CAF diet did not affect reproductive performance or fetal weight and length. However, CAF-fed animals showed a decrease in placental weight and index and the pups exhibited a low birth weight. Additionally, we found an upregulation of Igf2 and a down regulation of Vegf placental mRNA expression in CAF dams, associated with methylation status changes of their promoters. We conclude that female chronic CAF diet consumption impairs feto-placental development and could be explained by an epigenetic disruption of Igf and Vegf systems.