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 biochemical pathway that we have identified 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 the metabolism of a compound called betaine. A part of the betaine molecule called a methyl group is transferred to many other compounds in cells, and such "methylation" is instrumental in setting gene expression patterns among other important processes. We hope to show that creating the conditions in which this pathway can function normally in very early embryos will prevent some of the problems that arise in fetuses and placentas during pregnancy, and in babies.