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Unveiling the Role of MX1 and MX2 Gene Expression in Early Pregnancy of Kari Ewes: Insights into INF-tau Signaling and Potential as a Predictive Biomarker for Pregnancy Detection in Domestic Ruminants

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Open Access
Article Type Original Article
Subject Biology Group
OCLC JBRES Record
Taimur Khan, Ihtesham-ul-haq, Muhammad Shahab, Sohail Ahmad, Sher Hayat Khan* and Guojun Zheng*
Issue: Volume4-Issue8
Pages: 1170-1178
Received: 2023-07-06
Accepted: 2023-08-09
Published: 2023-08-10

Abstract

Myxovirus resistance (MX) genes are relevant to a family of interferon (IFN)-stimulated genes. In domestic ruminants such as ewes and cattle, the MX genes have two isoforms called the Myxovirus Resistance 1 (MX1) gene and the Myxovirus Resistance 2 (MX2) gene. INF-tau (INFt) is released from embryonic trophoblast cells in the early days of pregnancy and induces expression of MX genes in the uterine endometrium. In the present study, we summarized the relative expression of the MX1 and MX2 genes during the early days of pregnancy in Kari ewes. Blood samples were taken from inseminated and non-inseminated (control) ewes on different days. Peripheral Blood Monocytes (PBMC) were isolated, and with the addition of MX1 and MX2 gene primers, complementary deoxyribonucleic acid (cDNA) was synthesized by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The cDNA was then amplified by rounds of PCR amplification. The amplified product was run on a 2% Agarose gel. The results showed expression of the MX1 and MX2 genes only in pregnant ewes, while no expression was observed in non-pregnant or control ewes. Expression in pregnant ewes was observed on days 14, 16, 17, and 18 after insemination. When comparing the MX1 and MX2 genes, the expression of the MX2 gene was relatively higher than that of the MX1 gene on all experimental days. The result suggested that INF-tau MX genes are expressed during the early days of pregnancy and are involved in the establishment of pregnancy. These results justify the development of this biomarker as a predictive tool for the early detection of pregnancy in ewes and other domestic ruminants.

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© 2023 Khan T, et al. Distributed under Creative Commons CC-BY 4.0 Creative CommonsAttribution

How to cite this article

Khan T, Ihtesham-ul-haq, Shahab M, Ahmad S, Khan SH, Zheng G. Unveiling the Role of MX1 and MX2 Gene Expression in Early Pregnancy of Kari Ewes: Insights into INF-tau Signaling and Potential as a Predictive Biomarker for Pregnancy Detection in Domestic Ruminants. 2023 Aug 10; 4(8): 1170-1178. doi: 10.37871/jbres1783, Article ID: JBRES1783, Available at: https:// www.jelsciences.com/articles/jbres1783.pdf

Subject area(s)

Molecular BiomarkersGenetics

References

  1. Gray CA, Burghardt RC, Johnson GA, Bazer FW, Spencer TE. Evidence that absence of endometrial gland secretions in uterine gland knockout ewes compromises conceptus survival and elongation. Reproduction. 2002 Aug;124(2):289-300. PMID: 12141942.
  2. Bazer FW, Spencer TE, Johnson GA, Burghardt RC, Wu G. Comparative aspects of implantation. Reproduction. 2009 Aug;138(2):195-209. doi: 10.1530/REP-09-0158. Epub 2009 Jun 5. PMID: 19502456.
  3. Groebner AE, Rubio-Aliaga I, Schulke K, Reichenbach HD, Daniel H, Wolf E, Meyer HH, Ulbrich SE. Increase of essential amino acids in the bovine uterine lumen during preimplantation development. Reproduction. 2011 May;141(5):685-95. doi: 10.1530/REP-10-0533. Epub 2011 Mar 7. PMID: 21383026.
  4. Forde N, Simintiras CA, Sturmey R, Mamo S, Kelly AK, Spencer TE, Bazer FW, Lonergan P. Amino acids in the uterine luminal fluid reflects the temporal changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle. PLoS One. 2014 Jun 24;9(6):e100010. doi: 10.1371/journal.pone.0100010. PMID: 24960174; PMCID: PMC4069017.
  5. Thatcher W, Meyer M, Danet-Desnoyers G. Maternal recognition of pregnancy. Journal of Reproduction and Fertility-Supplements only. 1995;49:15-28.
  6. Hansen PJ, Tríbulo P. Regulation of present and future development by maternal regulatory signals acting on the embryo during the morula to blastocyst transition - insights from the cow. Biol Reprod. 2019 Sep 1;101(3):526-537. doi: 10.1093/biolre/ioz030. PMID: 31220231; PMCID: PMC8127039.
  7. Saugandhika S, Sharma V, Malik H, Saini S, Bag S, Kumar S, Singh NK, Mohanty AK, Malakar D. Expression and purification of buffalo interferon-tau and efficacy of recombinant buffalo interferon-tau for in vitro embryo development. Cytokine. 2015 Sep;75(1):186-96. doi: 10.1016/j.cyto.2015.03.012. Epub 2015 Apr 15. PMID: 25890875.
  8. Zhu D, Ott TL, Bazer FW. Enzyme-linked immunosorbent assay for ovine interferon-tau. J Interferon Cytokine Res. 1996 Feb;16(2):147-50. doi: 10.1089/jir.1996.16.147. PMID: 8742367.
  9. Ealy AD, Yang QE. Control of interferon-tau expression during early pregnancy in ruminants. Am J Reprod Immunol. 2009 Feb;61(2):95-106. doi: 10.1111/j.1600-0897.2008.00673.x. PMID: 19143673.
  10. Roberts RM. Interferon-tau, a Type 1 interferon involved in maternal recognition of pregnancy. Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):403-8. doi: 10.1016/j.cytogfr.2007.06.010. Epub 2007 Jul 27. PMID: 17662642; PMCID: PMC2000448.
  11. Bazer FW. Pregnancy recognition signaling mechanisms in ruminants and pigs. J Anim Sci Biotechnol. 2013 Jun 26;4(1):23. doi: 10.1186/2049-1891-4-23. PMID: 23800120; PMCID: PMC3710217.
  12. Kowalczyk A, Czerniawska-Piątkowska E, Wrzecińska M. The Importance of Interferon-Tau in the Diagnosis of Pregnancy. Biomed Res Int. 2021 Sep 2;2021:9915814. doi: 10.1155/2021/9915814. PMID: 34513997; PMCID: PMC8429012.
  13. Pugliesi G, Miagawa BT, Paiva YN, França MR, Silva LA, Binelli M. Conceptus-induced changes in the gene expression of blood immune cells and the ultrasound-accessed luteal function in beef cattle: how early can we detect pregnancy? Biol Reprod. 2014 Oct;91(4):95. doi: 10.1095/biolreprod.114.121525. Epub 2014 Sep 10. PMID: 25210129.
  14. Ruhmann B, Giller K, Hankele AK, Ulbrich SE, Schmicke M. Interferon-Ï„ induced gene expression in bovine hepatocytes during early pregnancy. Theriogenology. 2017 Dec;104:198-204. doi: 10.1016/j.theriogenology.2017.07.051. Epub 2017 Jul 31. PMID: 28888122.
  15. Spencer TE, Bazer FW. Conceptus signals for establishment and maintenance of pregnancy. Reprod Biol Endocrinol. 2004 Jul 5;2:49. doi: 10.1186/1477-7827-2-49. PMID: 15236653; PMCID: PMC471568.
  16. Shirasuna K, Matsumoto H, Kobayashi E, Nitta A, Haneda S, Matsui M, Kawashima C, Kida K, Shimizu T, Miyamoto A. Upregulation of interferon-stimulated genes and interleukin-10 in peripheral blood immune cells during early pregnancy in dairy cows. J Reprod Dev. 2012;58(1):84-90. doi: 10.1262/jrd.11-094k. Epub 2011 Nov 4. PMID: 22052007.
  17. Toji N, Koshi K, Furusawa T, Takahashi T, Ishiguro-Oonuma T, Kizaki K, Hashizume K. A cell-based interferon-tau assay with an interferon-stimulated gene 15 promoter. Biomed Res. 2018;39(1):13-20. doi: 10.2220/biomedres.39.13. PMID: 29467347.
  18. Gifford CA, Racicot K, Clark DS, Austin KJ, Hansen TR, Lucy MC, Davies CJ, Ott TL. Regulation of interferon-stimulated genes in peripheral blood leukocytes in pregnant and bred, nonpregnant dairy cows. J Dairy Sci. 2007 Jan;90(1):274-80. doi: 10.3168/jds.S0022-0302(07)72628-0. PMID: 17183095.
  19. Green JC, Okamura CS, Poock SE, Lucy MC. Measurement of interferon-tau (IFN-tau) stimulated gene expression in blood leukocytes for pregnancy diagnosis within 18-20d after insemination in dairy cattle. Anim Reprod Sci. 2010 Aug;121(1-2):24-33. doi: 10.1016/j.anireprosci.2010.05.010. Epub 2010 May 20. PMID: 20554404.
  20. Kizaki K, Shichijo-Kizaki A, Furusawa T, Takahashi T, Hosoe M, Hashizume K. Differential neutrophil gene expression in early bovine pregnancy. Reprod Biol Endocrinol. 2013 Feb 5;11:6. doi: 10.1186/1477-7827-11-6. PMID: 23384108; PMCID: PMC3570308.
  21. Matsuyama S, Kojima T, Kato S, Kimura K. Relationship between quantity of IFNT estimated by IFN-stimulated gene expression in peripheral blood mononuclear cells and bovine embryonic mortality after AI or ET. Reprod Biol Endocrinol. 2012 Mar 22;10:21. doi: 10.1186/1477-7827-10-21. PMID: 22439976; PMCID: PMC3364858.
  22. Forde N, Carter F, Spencer TE, Bazer FW, Sandra O, Mansouri-Attia N, Okumu LA, McGettigan PA, Mehta JP, McBride R, O'Gaora P, Roche JF, Lonergan P. Conceptus-induced changes in the endometrial transcriptome: how soon does the cow know she is pregnant? Biol Reprod. 2011 Jul;85(1):144-56. doi: 10.1095/biolreprod.110.090019. Epub 2011 Feb 23. PMID: 21349821.
  23. Geisert RD, Bazer FW, Regulation of implantation and establishment of pregnancy in mammals. Tribute to 45 Year Anniversary of Roger V. Short’s ‘Maternal Recognition of Pregnancy. Springer. 2015.
  24. Bott RC, Ashley RL, Henkes LE, Antoniazzi AQ, Bruemmer JE, Niswender GD, Bazer FW, Spencer TE, Smirnova NP, Anthony RV, Hansen TR. Uterine vein infusion of interferon tau (IFNT) extends luteal life span in ewes. Biol Reprod. 2010 Apr;82(4):725-35. doi: 10.1095/biolreprod.109.079467. Epub 2009 Dec 30. PMID: 20042537.
  25. Oliveira LJ, Hansen PJ. Deviations in populations of peripheral blood mononuclear cells and endometrial macrophages in the cow during pregnancy. Reproduction. 2008 Oct;136(4):481-90. doi: 10.1530/REP-08-0218. Epub 2008 Jul 17. PMID: 18635742.
  26. Köse M, Görgülü M, Kaya MS, Aydilek N, Bozkaya F, Bayril T, Kurar E, Kiyma Z, Güzeloğlu A, Atli MO. Expression profiles of Interferon-tau Stimulated Genes (ISGs) in Peripheral Blood Leucocytes (PBLs) and milk cells in pregnant dairy cows. 2014;20(2). doi:10.9775/kvfd.2013.9776.
  27. Hicks BA, Etter SJ, Carnahan KG, Joyce MM, Assiri AA, Carling SJ, Kodali K, Johnson GA, Hansen TR, Mirando MA, Woods GL, Vanderwall DK, Ott TL. Expression of the uterine Mx protein in cyclic and pregnant cows, gilts, and mares. J Anim Sci. 2003 Jun;81(6):1552-61. doi: 10.2527/2003.8161552x. PMID: 12817504.
  28. Horisberger MA, Gunst MC. Interferon-induced proteins: identification of Mx proteins in various mammalian species. Virology. 1991 Jan;180(1):185-90. doi: 10.1016/0042-6822(91)90022-4. PMID: 1984648.
  29. Haller O, Kochs G. Interferon-induced mx proteins: dynamin-like GTPases with antiviral activity. Traffic. 2002 Oct;3(10):710-7. doi: 10.1034/j.1600-0854.2002.31003.x. PMID: 12230469.
  30. Ahmad S. Gestation length of Kari sheep. Nature Precedings. 2008. doi: 10.1038/npre.2008.1620.1.
  31. Johnson GA, Joyce MM, Yankey SJ, Hansen TR, Ott TL. The Interferon Stimulated Genes (ISG) 17 and Mx have different temporal and spatial expression in the ovine uterus suggesting more complex regulation of the Mx gene. J Endocrinol. 2002 Aug;174(2):R7-R11. doi: 10.1677/joe.0.174r007. PMID: 12176677.
  32. Yankey SJ, Hicks BA, Carnahan KG, Assiri AM, Sinor SJ, Kodali K, Stellflug JN, Stellflug JN, Ott TL. Expression of the antiviral protein Mx in peripheral blood mononuclear cells of pregnant and bred, non-pregnant ewes. J Endocrinol. 2001 Aug;170(2):R7-11. doi: 10.1677/joe.0.170r007. PMID: 11479146.
  33. Bazer FW, Spencer TE, Ott TL, Ing NH. Regulation of endometrial responsiveness to estrogen and progesterone by pregnancy recognition signals during the periimplantation period. Springer. 1995;27-47.
  34. Ott TL, Yin J, Wiley AA, Kim HT, Gerami-Naini B, Spencer TE, Bartol FF, Burghardt RC, Bazer FW. Effects of the estrous cycle and early pregnancy on uterine expression of Mx protein in sheep (Ovis aries). Biol Reprod. 1998 Oct;59(4):784-94. doi: 10.1095/biolreprod59.4.784. PMID: 9746726.
  35. Shirozu T, Sasaki K, Kawahara M, Yanagawa Y, Nagano M, Yamauchi N, Takahashi M. Expression dynamics of bovine MX genes in the endometrium and placenta during early to mid pregnancy. J Reprod Dev. 2016;62(1):29-35. doi: 10.1262/jrd.2015-086. Epub 2015 Oct 26. PMID: 26498202; PMCID: PMC4768776.
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