Cell-Specific Expression of Enzymes for Serine Biosynthesis and Glutaminolysis in Farm Animals

During the peri-implantation period, conceptuses [embryo and placental membranes, particularly the trophectoderm (Tr)] of farm animals (e.g., sheep and pigs) rapidly elongate from spherical to tubular to filamentous forms. In concert with Tr outgrowth during conceptus elongation, the Tr of sheep and pig conceptuses attaches to the endometrial luminal epithelium (LE) to initiate placentation. In sheep, binucleate cells (BNCs) begin to differentiate from the mononuclear trophectoderm cells and migrate to the endometrial LE to form syncytial plaques. These events require Tr cells to expend significant amounts of energy to undergo timely and extensive proliferation, migration and fusion. It is likely essential that conceptuses optimally utilize multiple biosynthetic pathways to convert molecules such as glucose, fructose, and glutamine (components of histotroph transport by sheep and pig endometria into the uterine lumen), into ATP, amino acids, ribose, hexosamines and nucleotides required to support early conceptus development and survival. Elongating and proliferating conceptus Tr cells potentially act, in a manner similar to cancer cells, to direct carbon generated from glucose and fructose away from the TCA cycle for utilization in branching pathways of glycolysis, including the pentose phosphate pathway, one-carbon metabolism, and hexosamine biosynthesis. The result is a limited availability of pyruvate for maintaining the TCA cycle within mitochondria, and Tr cells replenish TCA cycle metabolites via a process known as anaplerosis, primarily through glutaminolysis to convert glutamine into TCA cycle intermediates. Here we describe the cell-specific expression of enzymes required for serine biosynthesis, one-carbon metabolism and glutaminolysis at the uterine-placental interface of sheep and pigs, and propose that these biosynthetic pathways are essential to support early placental development including Tr elongation, cell migration, cell fusion and implantation by ovine and porcine conceptuses.