Epigenetic disruption of placental genes bychronic maternal cafeteriadiet in rats

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

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

Cafeteria (CAF) diet is an experimental rodent model which reflectsvariety, palatability, and energy density food of western diet habits.Previous results indicated that CAF diet alters fertility and pregnancyperformance, although the mechanism involved remains unknown.Our aim was to study the effects of a maternal CAF diet on feto-placentalparameters on embryonic day 21 (E21) and analysed the implicationsof key placental systems: insulin growth factor (IGF) andvascular endothelial growth factor (VEGF). Female Wistar rats werefed with control (CON) diet (pellets) or CAF diet (i.e.: cheese snacks,sweet biscuits, and chocolate) from weaning. After 14th week offeeding, females were mated and half of the animals of each groupwere euthanized at E21. We determined fetal weight and length, andplacental weight and index (placental weight/fetal weight ratio). Therest of the animals were maintained until delivery with the respectivediet to assess the weight of pups at birth. Placentas were collectedfor mRNA quantification of IGF1, IGF1R, IGF2, IGF2R, VEGF andVEGFR 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-WhitneyU test was performed. CAF diet produced a decrease of placentalweight and index on E21 and a low weight of pups at birth. In addition,we found an upregulation of IGF2 and down regulation of VEGFplacental mRNA expression in CAF dams. Importantly, these changeswere associated with modifications in DNA methylation levels oftheir respective promoter regions. These results indicate that maternalCAF diet impairment of placental growth and pups weight at birthcould be explained, at least in part, with an epigenetic disruptionof IGF and VEGF systems. Identifying how epigenetic targets aredysregulated by diet factors will allow the development of preventionstrategies to improve human and animal reproductive health.