MECHANISMS OF PREIMPLANTATION DEVELOPMENTAL PROGRAMMING BY CHOLINE

It is the goal of animal scientists to improve the efficiency at which agriculturally-important animals produce products useful for man. Most commonly, enhanced production has been achieved through a combination of two strategies: selection of genes that are optimal for production and provision of a postnatal environment that maximizes the opportunity for those genes to be expressed. There is a third strategy that is only now being explored - regulation of the processes of prenatal development to produce a neonate poised for optimal production. Developmental programming is the phenomenon whereby changes in the environment of the developing organism or of the gametes from which it is derived reprograms aspects of development to modify postnatal phenotype. Exploitation of the phenomenon of developmental programming offers new opportunities for enhancing animal growthwhile also avoiding some negative perceptions by consumers of some other methods to increase muscle growth (e.g., growth promotants that could be considered as hormones by consumers).While the concept of developmental programming is well established, strategies to use this phenomenon to enhance animal production are poorly developed. We still do not understand how specific components of the maternalenvironment act on the developing embryo or fetus to program characteristics of the animal after birth. Here we will do experiemnts to distinguish between two potential mechanisms. One possibility is that choline induces epigenetic changes in DNA or histones that persist into fetal and postnatal life and cause changes in somatic growth. Another possibility is that choline acts to modify processes involved in lineage formation affect organ formation and postnatal growth. To evaluate the first possibility, we will test whether there are aa set of epigenetic marks modified by choline that persist into fetal and postnatal life To test the second possibility, we will test whetther choline causes changes in the distribution of the day 21 embryo into specific cell lineages.Gaining an increased knowledge of how a molecule like choline programs postnatal development could provide insights that inform other strategies for programming.One pertinent question is whether it is the changes in the epigenome of the preimplantation period that drive actions of choline on postnatal phenotype or whether other modifications induced by choline are important. Understanding how the maternal environment of the preimplantation embryo affects its development in the short- and long-term makes the proposed research directly relevant to the goal of the Animal Reproduction Program to study embryonic and fetal development including interaction between the conceptus and its uterine environment.