Effects of the environment on early mammalian embryo. Consequences for adult phenotype
Effets de l’environnement sur l’embryon de mammifères, conséquences pour le phénotype adulte
Résumé
In Mammals, fetal environment is known to affect adult health, giving rise to the DOHaD concept (Developmental Origin of Health and Disease). More recently, this concept of sensitivity to the environment with long term consequences has been extended to the periconceptional period. Especially, preimplantation period of development has been shown to be very sensitive to environmental conditions. This was quite unexpected since in most mammalian species, preimplantation development has been obtained in vitro and is compatible with full term development after transfer to a recipient mother. One of the most specific examples of such long term effect has been developed in the mouse model where females were fed a low protein diet for 3.5 days from fertilization onwards. This maternal diet skewed cell allocation to the first embryonic lineages at the blastocyst stage and induced a compensatory fetal and perinatal growth positively correlated to cardivascular, metabolic and behavioural abnormalities. In vitro development of mammalian embryo has also been reported to have long term effects, which is particularly worrisome within the framework of Assisted Reproductive Technologies. To analyze the effect of different environments on epigenetics modifications and on gene expression during the preimplantation period of development, we used the rabbit embryo as a model of early mammalian embryo with a delayed onset of embryonic genome activation, which is the case in most mammals (including human) except the mouse. In the rabbit, in vivo developed embryos can be easily recovered at each stage of development. We showed that the kinetics of embryonic genome de-methylation during the preimplantation development varies with embryo culture conditions and differs from in vivo development. We also modified the embryo environment in vivo by feeding rabbit females with an hyperlipidic/hypercholesterolemic diet. We showed that gene expression and trophoblast function were altered as soon as the blastocyst stage in such females.