Cell Signaling During Mammalian Early Embryo Development

Bazer, Fuller W, Johnson, Gregory A, Wu, G, Fuller W. Bazer, Gregory A. Johnson, G. Wu, Bazer, Fuller W., Johnson, Gregory A., Wu, G.

The dialogue between the mammalian conceptus (embryo/fetus and associated membranes) involves signaling for pregnancy recognition and maintenance of pregnancy during the critical peri-implantation period of pregnancy when the stage is set for implantation and placentation that precedes fetal development. Uterine epithelial cells secrete and/or transport a wide range of molecules, including nutrients, collectively referred to as histotroph that are transported into the fetal-placental vascular system to support growth and development of the conceptus. The availability of uterine-derived histotroph has long-term consequences for the health and well-being of the fetus and the prevention of Developmental Origins of Health and Disease (DOHAD). Although mechanisms responsible for differential growth and development of the conceptus resulting in DOHAD phenomena remain unclear, epigenetic events involving methylation of DNA are likely mechanisms. Histotroph includes serine and methionine which can contribute to the one carbon pool, and arginine, lysine and histidine residues which may be targets of methylation. It is also clear that supplementing the diet with arginine enhances fetal-placental development in rodents, swine and humans through mechanisms that remain to be elucidated. However, molecules secreted by conceptuses such as interferon tau in ruminants, estrogens and interferons in pigs and chorionic gonadotrophin, along with progesterone, regulate expression of genes for nutrient transporters. Understanding mechanisms whereby select nutrients regulate expression of genes in cell signaling pathways critical to conceptus development, implantation and placentation is required for improving successful establishment and maintenance of pregnancy in mammals.