Maternal diets have been shown to affect fetal development and postnatal health. However, their effects on early preimplantation embryo remain less documented. Feeding rabbit females with hyperlipidic (8%), hypercholesterolemic (0.2%) diet (HH diet) from 10 weeks of age resulted in intrauterine growth retardation of the progeny as soon as day 9 post fertilization.1 We thus wondered whether early embryo was affected by this maternal diet. Therefore, we compared the transcriptome of embryos developed in HH-fed females with that of their control (C) counterparts at the stage just following the onset of embryonic genome activation (16–20 cell stage). Our transcriptome analyses evidenced the overexpression of ADIPOPHILIN in HH embryos. ADIPOPHILIN encodes for a protein involved in the early steps of lipid droplets formation from the endoplasmic reticulum. Its overexpression at embryonic genome activation stage was confirmed by quantitative RT-PCR analyses. It seems to be transient as transcript quantification at the blastocyst stage did not detect significant differences between HH and C embryos. However, very interestingly, immuno- cytochemical analysis of ADIPOPHILIN localization at the blastocyst stage showed that ADIPOPHILIN colocalized with Nile Red-stained lipid droplets in the cytoplasm of trophoblast cells in HH embryos. Such lipid droplets accumulation was not found in control embryos. Later on, during gestation, HH conceptuses displayed similar lipid droplets in the labyrinthine zone of their placenta, whereas C conceptuses did not. Thus, our results evidenced that embryo gene expression may be sensitive to maternal diet as early as embryonic genome activation stage, and gene deregulation may be involved in early perturbation of extraembryonic tissues that persists during pregnancy.