Arginine and Secreted Phosphoprotein 1 Mediate Cell Signaling to Enhance Conceptus Development and Survival
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Embryonic death losses of 20 to 30 percent in sheep can be reduced by supplemental dietary arginine through undefined mechanisms. Knockdown ornithine decarboxylase (ODC1) mRNA translation results in normal and abnormal conceptuses. Normal conceptuses increase production of polyamines via the arginine decarboxylase (ADC) and agmatinase (AGMAT) pathway, whereas abnormal conceptuses do not activate that pathway for production of polyamines. Therefore, this application focuses on products of arginine metabolism, specifically agmatine and putrescine, acting in concert with secreted phosphoprotein 1 (SPP1), that activate mechanistic target of rapamacin (MTORC1 and MTORC2) cell signaling to stimulate proliferation, migration, cytoskeletal organization and gene expression required for implantation and expression of IFNT for pregnancy recognition. We hypothesize that arginine, agmatine and polyamines alone or with SPP1 activate MTORC1 and MTORC2 to stimulate conceptus development and that progesterone therapy from Day 2 of pregnancy increases transport of arginine and secretion of SPP1 by uterine glandular epithelia to accelerate conceptus development. Specific objectives are to determine cell signaling pathway(s) activated by arginine, agmatine and polyamines that stimulate development and gene expression by conceptuses; effects of knockdown of translation of ADC and AGMAT mRNAs on conceptus development; effects of SPP1 on cytoskeletal organization and conceptus elongation; and effects of circulating concentrations of progesterone from Day 2 of pregnancy on conceptus development.