Grant: Operating Grant

There is strong evidence that the mother's nutrition, health, and environment during the earliest stages of pregnancy immediately after conception can significantly affect the health of the embryo and the fetus and placenta into which it develops. Also, the treatment of human infertility by assisted reproduction technologies (ART), in which multiple eggs are obtained from women, fertilized, and cultured for an extended period before being transferred into the uterus, has been very effective and produced millions of babies, but there is increasing evidence that how eggs and very early embryos are handled during ART can cause health problems in the fetus, placenta, and offspring. In this work, we will be investigating mechanisms that may be important in causing such problems, concentrating on one set of biochemical pathways that we have studied in embryos that may be involved in setting up patterns of gene expression in the fetal/placental unit that can then last throughout life. This pathway involves "methyl groups." Methyl groups are transferred to many other compounds in cells including DNA (the genes), and such "methylation" is instrumental in determining which genes are active. We have found that the methyl groups in embryos come not only from folic acid like in most cells, but also from a compound called betaine. We hope to show that creating the conditions in which these pathways can function normally in eggs and very early embryos will prevent some of the problems that arise in fetuses and placentas during pregnancy, and in babies.