High fat maternal diet impacts the nutrient sensing signaling network in rabbit blastocyst
Résumé
The periconceptional period is recognised as a particularly vulnerable period for environ mental programming. Maternai nutrition during developmental stages may trigger effects on several physiological functions of the organism. We have previously shown that a maternai lipid and cholesterol-enriched diet (HH diet) administred to rabbit does from prepubertal period and throughout gestation induces fetal growth retardation and components of the metabolic syndrome in adult offspring. HH diet induces lipid droplet accumulation at the blastocyst stage. We aimed to identify the impact of maternai HH diet on rabbit blastocyst gene expression. We perforrned transcriptomic profiles of blastocysts obtained frorn rabbit does fed with either a HH diet (n=15) or a control diet (n=l2). For this purpose, customized rabbit rnicroarray (Agilent Technologies, GEO platform GPL16709) was used. Statistical analysis (Lirnma) revealed 4 probes differentially expressed in HH vs control blastocysts (padj< 0.05). We were able to annotate 26 genes, 16 up and 10 down-regulatecl. Functional classification based on GO terrns indicated that differentially expressed genes are mainly implicated in lipid transporter activity (RBP4, SCP2) and glucose metabolic process (RBP4, PGD, OMAl) . In addition to this approach, we used Gene Set Enrichment Analysis (GSEA) to identify significant enrichment of gene sets (FDR< 0.25, p< 0.05). Beyond the confirmation of deregulation of glucose and lipid metabolisms, GSEA highlighted enrichrnent of rnTORCl, a rnaster growth regulator that senses growth factors, arnino acids, energy status levels to regulate cell growth, proliferation and lipid metabolism. In conclusion, we demonstrated that maternal HH diet altered nutrient sensing and cellular rnetabolism in blastocyst. These transcriptomic datas will be soon inte grated with metabolornic datas obtained on HH and control blastocoelic fluids using ultrasouncl biomicroscopy puncture by NMR.