High glucose disturbs different developmental parameters of the mouse blastocyst in vitro

Diabetic embryopathy is the leading cause of neonatal death and I or congenital malformations in diabetic mothers’infants. In response to the difficulties with pregnancy outcome, there has been much effort to extend understanding of the disruptive mechanisms involved in diabetic embryopathy. Most of our knowledge on the deleterious influence of maternal diabetes on embryo development comes from experimental studies on rodent embryos undergoing organogenesis. These studies have demonstrated the embryotoxicity of diabetic serum and the implication of glucose as a direct teratogen. Much less studies have been performed during the pré-implantation period of embryo development. However, there is increasing recognition that poorly controlled maternal diabetes before the time of implantation may be an important risk factor for fetal complications in the human population. One of the most determinant events that occur during the pré-implantation period is the first cell differentiation with the emergence of two stem cell lineages: the embryoblast or Inner Cell Mass which will form the fetus and the trophectoderm which will form the placenta. The changes induced in the uterine environment by maternal diabetes may disrupt at this stage of development, the differentiation and proliferation of both cell lineages that could have severe consequences on further embryo development. This study will investigate the influence of high glucose concentrations on the in vitro development of the mouse pré-implantation embryo and particularly the differential impact of glucose on the two cell lineages composing the blastocyst stage embryo. The first part of this work will present different developmental aspects of the pré-implantation embryo and particularly of the blastocyst stage embryo. We will also summarize observations reported in vivo and in vitro by previous studies of the deleterious impact of diabetes on rodent pré-implantation embryos. Finally, some concepts proposed to explain the diabetic embryopathy in the post-implantation rodent embryos would be presented. Personal contribution in this area of research will follow with three manuscripts investigating the impact of high glucose concentrations on mouse blastocyst cell death and differentiation. The main results and perpectives will be discussed in the final part of the thesis.Thèse de doctorat en sciences biomédicales (biologie du développement) (SBIM 3) --UCL, 200