The prevalence of Type 2 Diabetes is continuously increasing worldwide. Nowadays younger populations are affected, including women of childbearing age. The in utero exposure to hyperglycemia and/or hyperinsulinemia is associated with metabolic perturbations during the life course of the individual including an increased risk to develop metabolic diseases at adult age, as described by the developmental origins of health and disease (DOHaD). One of the most sensitive periods of the in utero life corresponds to the preimplantation period. Preimplantation development is characterized by highly regulated events, including the first cell differentiation of the inner cell mass (ICM), the future individual, and the trophectoderm (TE), that contributes to the formation of the placenta.
In this context, we are interested in the effect of hyperglycemia and/or hyperinsulinemia exposure on preimplantation embryos, but more precisely on the ICM and TE. Hence, we developed an in vitro model of rabbit embryos exposed to high glucose and/or high insulin from 1-cell to the blastocyst stage. In vitro-developed blastocysts were collected, and the ICM and TE were isolated to perform transcriptome profiling by RNA-seq. Transcriptome analysis indicates the deregulation of signaling pathways and biological processes implicated in transcription, translation, chromatin remodeling, cell differentiation, energy metabolism, and cell allocation. To better characterize the effects observed, our next step will be to map the landscape of chromatin accessibility of the ICM and TE by ATAC-seq and to integrate the ATAC-seq profiles to the transcriptome profiles to determine whether changes in chromatin dynamics correlate with the gene expression changes. Investigating the effects of high glucose and/or high insulin during the first stages of embryonic development could help better understand the molecular mechanisms behind the establishment of programming to disease later in life.
