title: Uterine histotroph and conceptus development. I. cooperative effects of arginine and secreted phosphoprotein 1 on proliferation of ovine trophectoderm cells via activation of the PDK1-Akt/PKB-TSC2-MTORC1 signaling cascade.
abstract: The greatest limitation to reproductive performance in most mammals, including humans, is embryonic mortality, which, in general, claims 20%-40% of the embryos during the peri-implantation period of pregnancy. Both arginine and secreted phosphoprotein 1 (SPP1) are multifunctional molecules that increase significantly in ovine uterine histotroph during early pregnancy. However, little is known about the relationship and underlying mechanisms for synergistic effects of arginine and SPP1, if any, on conceptus (embryo/fetus and associated extraembryonic membranes) development. Therefore, we conducted in vitro experiments using our established ovine trophectoderm cell line (oTr1) isolated from Day 15 ovine conceptuses to determine their proliferative response to individual and synergistic effects of arginine and recombinant SPP1 (rSPP1) that contains an RGD binding sequence. At physiological concentrations, arginine (0.2 mM) stimulated oTr1 cell proliferation 1.7-fold (P < 0.05) at 48 h, whereas rSPP1 (10 ng/ml) had no such effect. However, an additive effect on oTr1 cell proliferation was induced by combination of arginine and SPP1 as compared to the control (2.1-fold increase; P < 0.01), arginine alone (1.3-fold increase; P < 0.05), and rSPP1 alone (1.5-fold increase; P < 0.01). This additive effect was mediated through cooperative activation of the PDK1-Akt/PKB-TSC2-MTORC1 cell signaling cascade. Collectively, results suggest that arginine and SPP1 in histotroph act cooperatively to enhance survival, growth, and development of ovine conceptuses.
authors.affiliation: Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, Texas Department of Animal Science, Texas A&M University, College Station, Texas.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Johnson
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Burghardt
authors.affiliation: Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, Texas Department of Animal Science, Texas A&M University, College Station, Texas.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.affiliation: Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, Texas Department of Animal Science, Texas A&M University, College Station, Texas fbazer@cvm.tamu.edu.
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D053495:Osteopontin / Q000494:pharmacology*; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D053495:Osteopontin; D001120:Arginine; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: MTORC1; SPP1; arginine; sheep; trophectoderm