EPIGENETIC DISRUPTION OF PLACENTAL GENES BY CHRONIC MATERNAL CAFETERIA DIET IN RATS

GASTIAZORO, MP; STOKER, C.; VARAYOUD J; ROSSETTI, MF; SCHUMACHER, R; DURANDO, M.; RAMOS JG

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Cafeteria (CAF) diet is an experimental rodent model which reflects variety, palatability, and energy density food of western diet habits. Previous results indicated that CAF diet alters fertility and pregnancy performance, although the mechanism involved remains unknown. Our aim was to study the effects of a maternal CAF diet on feto-placental parameters on embryonic day 21 (E21) and analysed the implications of key placental systems: insulin growth factor (IGF) and vascular endothelial growth factor (VEGF). Female Wistar rats were fed with control (CON) diet (pellets) or CAF diet (i.e.: cheese snacks, sweet biscuits, and chocolate) from weaning. After 14th week of feeding, females were mated and half of the animals of each group were euthanized at E21. We determined fetal weight and length, and placental weight and index (placental weight/fetal weight ratio). The rest of the animals were maintained until delivery with the respective diet to assess the weight of pups at birth. Placentas were collected for mRNA quantification of IGF1, IGF1R, IGF2, IGF2R, VEGF and VEGFR and for DNA methylation analysis of their promoter regions. Feto-placental parameters were analyzed using Student´s T test; for mRNA expression and DNA methylation levels a Mann-Whitney U test was performed. CAF diet produced a decrease of placental weight and index on E21 and a low weight of pups at birth. In addition, we found an upregulation of IGF2 and down regulation of VEGF placental mRNA expression in CAF dams. Importantly, these changes were associated with modifications in DNA methylation levels of their respective promoter regions. These results indicate that maternal CAF diet impairment of placental growth and pups weight at birth could be explained, at least in part, with an epigenetic disruption of IGF and VEGF systems. Identifying how epigenetic targets are dysregulated by diet factors will allow the development of prevention strategies to improve human and animal reproductive health.