Alteration of the embryonic microenvironment and sex-specific responses of the preimplantation embryo related to a maternal high-fat diet in the rabbit model

Abstract

The maternal metabolic environment can be detrimental to the health of the offspring. In a previous work, we showed that maternal high-fat (HH) feeding in rabbit induced sex-dependent metabolic adaptation in the fetus and led to metabolic syndrome in adult offspring. As early development representing a critical window of susceptibility, in the present work we aimed to explore the effects of the HH diet on the oocyte, preimplantation embryo and its microenvironment. In oocytes from females on HH diet, transcriptomic analysis revealed a weak modification in the content of transcripts mainly involved in meiosis and translational control. The effect of maternal HH diet on the embryonic microenvironment was investigated by identifying the metabolite composition of uterine and embryonic fluids collected in vivo by biomicroscopy. Metabolomic analysis revealed differences in the HH uterine fluid surrounding the embryo, with increased pyruvate concentration. Within the blastocoelic fluid, metabolomic profiles showed decreased glucose and alanine concentrations. In addition, the blastocyst transcriptome showed under-expression of genes and pathways involved in lipid, glucose and amino acid transport and metabolism, most pronounced in female embryos. This work demonstrates that the maternal HH diet disrupts the in vivo composition of the embryonic microenvironment, where the presence of nutrients is increased. In contrast to this nutrient-rich environment, the embryo presents a decrease in nutrient sensing and metabolism suggesting a potential protective process. In addition, this work identifies a very early sex-specific response to the maternal HH diet, from the blastocyst stage.

The Effect of Maternal Exposure to a Diet High in Fats and Cholesterol on the Placental Function and Phenotype of the Offspring in a Rabbit Model: A Summary Review of About 15 Years of Research

“…The difference in adipophilin gene expression observed between the 16-20 cell and blastocyst stages could be due to a rapid regulatory loop aimed at limiting the accumulation of droplets in the embryo, as it is known that a decrease in adipophilin reduces the formation of lipid droplets [56]. Furthermore, it could also be an adaptive response to the maternal H environment related to the contents of the uterine fluid, because the H environment differed from the C group [57], or to an alteration of follicular fluid contents in the oocyte, as evidenced in humans [58] and cattle [59].…”