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Functional roles of ornithine decarboxylase and arginine decarboxylase during the peri-implantation period of pregnancy in sheep

摘要Background: Polyamines stimulate DNA transcription and mRNA translation for protein synthesis in trophectoderm cells, as well as proliferation and migration of cells; therefore, they are essential for development and survival of conceptuses (embryo/fetus and placenta). The ovine conceptus produces polyamines via classical and non-classical pathways. In the classical pathway, arginine (Arg) is transformed into ornithine, which is then decarboxylated by ornithine decarboxylase (ODC1) to produce putrescine which is the substrate for the production of spermidine and spermine. In the non-classical pathway, Arg is converted to agmatine (Agm) by arginine decarboxylase (ADC), and Agm is converted to putrescine by agmatinase (AGMAT). Methods: Morpholino antisense oligonucleotides (MAOs) were designed and synthesized to inhibit translational initiation of the mRNAs for ODC1 and ADC, in ovine conceptuses.Results: The morphologies of MAO control, MAO-ODC1, and MAO-ADC conceptuses were normal. Double knockdown of ODC1 and ADC (MAO-ODC1:ADC) resulted in two phenotypes of conceptuses; 33% of conceptuses appeared to be morphologically and functionally normal (phenotype a) and 67% of the conceptuses presented an abnormal morphology and functionality (phenotype b). Furthermore, MAO-ODC1:ADC (a) conceptuses had greater tissue concentrations of Agm, putrescine, and spermidine than MAO control conceptuses, while MAO-ODC1:ADC (b) conceptuses only had greater tissue concentrations of Agm. Uterine flushes from ewes with MAO-ODC1:ADC (a) had greater amounts of arginine, aspartate, tyrosine, citrulline, lysine, phenylalanine, isoleucine, leucine, and glutamine, while uterine flushes of ewes with MAO-ODC1:ADC (b) conceptuses had lower amount of putrescine, spermidine, spermine, alanine, aspartate, glutamine, tyrosine, phenylalanine, isoleucine, leucine, and lysine.Conclusions: The double-knockdown of translation of ODC1 and ADC mRNAs was most detrimental to conceptus development and their production of interferon tau (IFNT). Agm, polyamines, amino acids, and adequate secretion of IFNT are critical for establishment and maintenance of pregnancy during the peri-implantation period of gestation in sheep.

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作者单位 Department of Animal Science, Texas A&M University, College Station, TX 77843-2471, USA;Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, TX 77843, USA;Centauro Research Group, School of Veterinary Medicine, Faculty of Agrarian Science, Universidad de Antioquia, Calle 70 No, 52-21 Medellín, Colombia;Faculty of Agricultural Sciences, Calle 222 No. 55-37, UDCA, Bogota, Colombia [1] Department of Animal Science, Texas A&M University, College Station, TX 77843-2471, USA;Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, TX 77843, USA [2] Department of Animal Science, Texas A&M University, College Station, TX 77843-2471, USA;Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, TX 77843, USA;National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA [3] Department of Animal Science, Texas A&M University, College Station, TX 77843-2471, USA [4] Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA [5]
DOI 10.1186/s40104-017-0225-x
发布时间 2018-08-01(万方平台首次上网日期,不代表论文的发表时间)
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