Abstract
This study investigated the effect of agmatine (Agm) in proliferation of ovine trophecdoderm cells (oTr1) as well as the importance of the arginine decarboxylase (ADC) and agmatinase (AGMAT) alternative pathway for synthesis of polyamines in ovine conceptuses during the peri-implantation period of pregnancy. Morpholino antisense oligonucleotides (MAOs) were used to inhibit translation of mRNAs for ODC1 alone, AGMAT alone, and their combination. Rambouillet ewes (N = 50) were assigned randomly to the following treatments on Day 8 of pregnancy: MAO control (n = 10); MAO-ODC1 (n = 8); MAO-ADC (n = 6); MAO-ODC1:MAO-ADC (n = 9); or MAO-ODC1:MAO-AGMAT (n = 9). Ewes were ovario-hysterectomized on Day 16 of pregnancy to obtain uterine flushings, uterine endometrium, and conceptus tissues. Inhibition of translation of both ODC1 and AGMAT resulted in 22% of ewes having morphologically and functionally normal (elongated and healthy) conceptuses designated MAO-ODC1:MAO-AGMAT (A). But, 78% of the MAO-ODC1:MAO-AGMAT ewes had morphologically and functionally abnormal (not elongated and fragmented) conceptuses designated MAO-ODC1:MAO-AGMAT (B). The pregnancy rate was less (22%; P < 0.05) for MAO-ODC1:MAO-AGMAT ewes than for MAO-control (80%), MAO-ODC1 (75%), MAO-ADC (84%), and MAO-ODC1:MAO-ADC (44%) ewes. Moreover, inhibition of translational of both ODC1 and AGMAT mRNAs increased expression of ADC, SLC22A1, SLC22A2, and SLC22A3 mRNAs, as well as abundances of agmatine, putrescine, spermindine, and spermine in conceptus tissue. However, MAO-ODC1:AGMAT(B) ewes had greater abundances of agmatine, putrescine, and spermidine and reduced amounts of spermine in uterine flushes. Thus, in vivo knockdown of translation of ODC1 and AGMAT mRNAs increased expression of genes for the synthesis and transport of polyamines in ovine conceptuses during the peri-implantation period of pregnancy.
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Abbreviations
- ADC :
-
Arginine decarboxylase
- AGMAT:
-
Agmatinase
- Arg:
-
l-arginine
- Agm:
-
Agmatine
- OAZ:
-
Antienzyme
- MAO:
-
Morpholino
- IFNT:
-
Interferon tau
- IGF2:
-
Insulin growth factor type 2
- NO:
-
Nitric oxide
- ODC1 :
-
Ornithine decarboxylase
- SLC22A1:
-
Organic cationic transporter type 1
- SLC22A2:
-
Organic cationic transporter type 2
- SLC22A3:
-
Organic cationic transporter type 3
- SLC7A1:
-
Solute carrier family 7 member 1
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Acknowledgements
Funding from the Sustainability Strategy 2013–2014, from CODI University of Antioquia (UdeA), Medellín, Colombia Scholarship “Becas Doctorado UdeA 2014” was used to support YYL, a PhD student in Veterinary Science, Faculty of Agrarian Science, Antioquia University). Funding for the research and related activities was from the Agriculture and Food Research Initiative Competitive Grants (2016-67015-24958 to FWB and 2015-67015-23276 to GW) from the USDA National Institute of Food and Agriculture.
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All experimental and surgical procedures were approved by the Institutional Animal Care and Use Committee at Texas A&M University.
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Handling Editor: F. Erdmann.
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Lenis, Y.Y., Elmetwally, M.A., Tang, W. et al. Functional roles of agmatinase during the peri-implantation period of pregnancy in sheep. Amino Acids 50, 293–308 (2018). https://doi.org/10.1007/s00726-017-2515-1
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DOI: https://doi.org/10.1007/s00726-017-2515-1