Grant: Project 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 damage eggs before fertilization and can cause health problems in the fetus, placenta, and offspring. In this work, we will be investigating mechanisms that may be important in preventing such problems. We are focusing on a molecule called betaine, which is a modified form of the common amino acid glycine. Betaine is supplied in the diet, for example by wheat germ, spinach, and shellfish. It can also be synthesized in the body from the vitamin, choline. We have previously found that betaine has important roles in mammalian eggs and very early embryos. One function is to control cell size, which turns out to be particularly critical for early embryo health. Another role is in supplying the molecules needed for controlling gene activity in later embryos, just before they implant in the uterus. We also have new evidence that betaine is also involved in the normal function of mitochondria, which are the part of the cell that makes energy, in eggs. How betaine is supplied to the egg and embryo, where it comes from, and the consequences of its dysregulation, are still poorly understood. We hope to show that creating the conditions in which these mechanisms can function normally in eggs and very early embryos will produce healthy eggs and embryos.