2016 Elsevier Inc. All rights reserved. Embryonic mortality is a major constraint to reproductive performance in all mammals. Estimates of embryonic death in most mammals, including swine, sheep, cattle, and humans, ranges from 20% to 40%, with two-thirds of the losses occurring during the peri-implantation period of pregnancy. During that stage of pregnancy, the dialog between the mammalian conceptus (embryo/fetus and associated membranes) and maternal uterus involves signaling for pregnancy recognition and maintenance of pregnancy as 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. This review provides a framework for studies of constituents, including hexose sugars (i.e., glucose and fructose), extracellular matrix proteins (e.g., secreted phosphoprotein 1), amino acids (e.g., arginine, leucine, and glutamine), and their metabolites (e.g., nitric oxide and polyamines) that independently and cooperatively activate nutrient-sensing cell signaling pathways, particularly mechanistic target of rapamycin (mTOR), the master regulator of cell growth (proliferative growth via mTORC1 and spatial growth via mTORC2), for growth, development, and survival of conceptuses, as well as for the optimization of culture media for in vitro studies of conceptus development. Understanding the relationships between cell signaling pathways and developmental events is critical for enhancing conceptus development, implantation, and placentation, thereby increasing the probability for birth of healthy offspring.
