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Biol Reprod. 2016 Sep;95(3):71. doi: 10.1095/biolreprod.115.137943. Epub 2016 Aug 10.

Uterine Histotroph and Conceptus Development. II. Arginine and Secreted Phosphoprotein 1 Cooperatively Stimulate Migration and Adhesion of Ovine Trophectoderm Cells via Focal Adhesion-MTORC2 Mediated Cytoskeleton Reorganization.

Biology of reproduction

Xiaoqiu Wang, Greg A Johnson, Robert C Burghardt, Guoyao Wu, Fuller W Bazer

Affiliations

  1. Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, Texas Department of Animal Science, Texas A&M University, College Station, Texas.
  2. Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas.
  3. Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, Texas Department of Animal Science, Texas A&M University, College Station, Texas [email protected].

PMID: 27512152 DOI: 10.1095/biolreprod.115.137943

Abstract

In all mammalian species, critical events, including uterine receptivity and development of the conceptus (embryo/fetus and its associated extraembryonic membranes), must be intricately orchestrated and carefully timed during the window of implantation. Otherwise, failure of conceptuses to implant is inevitable, which accounts for 50%-75% of failures to establish pregnancy. Unlike human and rodent blastocysts, the blastocysts of pigs and ruminants undergo rapid transitions from spherical to tubular and filamentous conceptuses in response to histotroph during the peri-implantation period of pregnancy. Both arginine and secreted phosphoprotein 1 (SPP1; also known as osteopontin) are multifunctional molecules that increase significantly in ovine uterine histotroph during early pregnancy; however, little is known about their relationship and synergistic effects on conceptus development. Therefore, we conducted in vitro experiments using our established ovine trophectoderm cell line (oTr1) isolated from Day 15 ovine conceptuses to determine their migratory and adhesive responses to individual and combined effects of arginine and recombinant SPP1 (rSPP1) that contains an Arg-Gly-Asp (RGD) binding sequence. Migration and adhesion of oTr1 cells were significantly stimulated by rSPP1, whereas arginine alone only induced a significant increase in cell migration. However, the combination of arginine and rSPP1 had an additive effect on migration, and a synergistic effect on adhesion of oTr1 cells. Those cooperative effects of arginine and SPP1 were mediated by focal adhesion assembly-MTORC2-cytoskeletal reorganization and MAPK pathways. Collectively, results suggest that arginine and SPP1 in histotroph affect cellular events required for rapid elongation of ovine conceptuses during the peri-implantation period of pregnancy.

© 2016 by the Society for the Study of Reproduction, Inc.

Keywords: MTORC2; SPP1; arginine; cytoskeleton reorganization; sheep; trophectoderm

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