Animal Bioscience

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
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Conceptus-derived cytokines interleukin-1β and interferon-γ induce the expression of acute phase protein serum amyloid A3 in endometrial epithelia at the time of conceptus implantation in pigs

  • Soohyung Lee (Division of Biological Science and Technology, Yonsei University) ;
  • Inkyun Yoo (Division of Biological Science and Technology, Yonsei University) ;
  • Yugyeong Cheon (Division of Biological Science and Technology, Yonsei University) ;
  • Hakhyun Ka (Division of Biological Science and Technology, Yonsei University)
  • Received : 2022.08.31
  • Accepted : 2022.10.05
  • Published : 2023.03.01
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Abstract

Objective: Serum amyloid A3 (SAA3), an acute phase response protein, plays important roles in opsonization, antimicrobial activity, chemotactic activity, and immunomodulation, but its expression, regulation, and function at the maternal-conceptus interface in pigs are not fully understood. Therefore, we determined the expression of SAA3 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy. Methods: Endometrial tissues from pigs at various stages of the estrous cycle and pregnancy and with conceptuses derived from somatic cell nuclear transfer (SCNT), conceptus tissues during early pregnancy, and chorioallantoic tissues during mid- to late pregnancy were obtained and the expression of SAA3 was analyzed. The effects of the steroid hormones, interleukin-1β (IL1B), and interferon-γ (IFNG) on the expression of SAA3 were determined in endometrial explant cultures. Results: SAA3 was expressed in the endometrium during the estrous cycle and pregnancy, with the highest level on day 12 of pregnancy. The expression of SAA3 in the endometrium was significantly higher on day 12 of pregnancy than during the estrous cycle. Early-stage conceptuses and chorioallantoic tissues during mid to late pregnancy also expressed SAA3. The expression of SAA3 was primarily localized to luminal epithelial cells in the endometrium. In endometrial explant cultures, the expression of SAA3 was induced by increasing doses of IL1B and IFNG. Furthermore, the expression of SAA3 decreased significantly in the endometria of pigs carrying conceptuses derived from SCNT on day 12 of pregnancy. Conclusion: These results suggest that the expression of SAA3 in the endometrium during the implantation period increases in response to conceptus-derived IL1B and IFNG. The failure of those appropriate interactions between the implanting conceptus and the endometrium leads to dysregulation of endometrial SAA3 expression, which could result in pregnancy failure. In addition, SAA3 could be a specific endometrial epithelial marker for conceptus implantation in pigs.

Keywords

Acknowledgement

This study was supported by the National Research Foundation grant funded by the Korean Government (NRF-2019R1A2 C1004670), Korea.

References

  1. Ka H, Seo H, Choi Y, Yoo I, Han J. Endometrial response to conceptus-derived estrogen and interleukin-1beta at the time of implantation in pigs. J Anim Sci Biotechnol 2018;9:44. https://doi.org/10.1186/s40104-018-0259-8
  2. Bazer FW, Wu G, Spencer TE, Johnson GA, Burghardt RC, Bayless K. Novel pathways for implantation and establishment and maintenance of pregnancy in mammals. Mol Hum Reprod 2010;16:135-52. https://doi.org/10.1093/molehr/gap095
  3. Bazer FW, Johnson GA. Pig blastocyst-uterine interactions. Differentiation 2014;87:52-65. https://doi.org/10.1016/j.diff.2013.11.005
  4. Ka H, Seo H, Kim M, Choi Y, Lee CK. Identification of differentially expressed genes in the uterine endometrium on day 12 of the estrous cycle and pregnancy in pigs. Mol Reprod Dev 2009;76:75-84. https://doi.org/10.1002/mrd.20935
  5. Urieli-Shoval S, Linke RP, Matzner Y. Expression and function of serum amyloid A, a major acute-phase protein, in normal and disease states. Curr Opin Hematol 2000;7:64-9. https://doi.org/10.1097/00062752-200001000-00012
  6. Dalla Vestra M, Mussap M, Gallina P, et al. Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J Am Soc Nephrol 2005;16(Suppl 1): S78-82. https://doi.org/10.1681/asn.2004110961
  7. Malle E, Sodin-Semrl S, Kovacevic A. Serum amyloid A: an acute-phase protein involved in tumour pathogenesis. Cell Mol Life Sci 2009;66:9. https://doi.org/10.1007/s00018-008-8321-x
  8. Olsen HG, Skovgaard K, Nielsen OL, et al. Organization and biology of the porcine serum amyloid A (SAA) gene cluster: isoform specific responses to bacterial infection. PLoS One 2013;8:e76695. https://doi.org/10.1371/journal.pone.0076695
  9. Soler L, Luyten T, Stinckens A, Buys N, Ceron JJ, Niewold TA. Serum amyloid A3 (SAA3), not SAA1 appears to be the major acute phase SAA isoform in the pig. Vet Immunol Immunopathol 2011;141:109-15. https://doi.org/10.1016/j.vetimm.2011.02.019
  10. Sack GH, Jr. Serum amyloid A - a review. Mol Med 2018;24:46. https://doi.org/10.1186/s10020-018-0047-0
  11. Canisso IF, Segabinazzi L, Fedorka CE. Persistent breeding-induced endometritis in mares - a multifaceted challenge: from clinical aspects to immunopathogenesis and pathobiology. Int J Mol Sci 2020;21:1432. https://doi.org/10.3390/ijms21041432
  12. Cocco E, Bellone S, El-Sahwi K, et al. Serum amyloid A: a novel biomarker for endometrial cancer. Cancer 2010;116: 843-51. https://doi.org/10.1002/cncr.24838
  13. Sandri S, Urban Borbely A, Fernandes I, et al. Serum amyloid A in the placenta and its role in trophoblast invasion. PLoS One 2014;9:e90881. https://doi. org/10.1371/journal.pone.0090881
  14. Czernik M, Anzalone DA, Palazzese L, Oikawa M, Loi P. Somatic cell nuclear transfer: failures, successes and the challenges ahead. Int J Dev Biol 2019;63:123-30. https://doi.org/10.1387/ijdb.180324mc
  15. Matoba S, Zhang Y. Somatic cell nuclear transfer reprogramming: mechanisms and applications. Cell Stem Cell 2018;23: 471-85. https://doi.org/10.1016/j.stem.2018.06.018
  16. Ka H, Seo H, Kim M, Moon S, Kim H, Lee CK. Gene expression profiling of the uterus with embryos cloned by somatic cell nuclear transfer on day 30 of pregnancy. Anim Reprod Sci 2008;108:79-91. https://doi.org/10.1016/j.anireprosci.2007.07.008
  17. Kim M, Seo H, Choi Y, Hwang W, Lee CK, Ka H. Aberrant expression of retinol-binding protein, osteopontin and fibro-blast growth factor 7 in the porcine uterine endometrium of pregnant recipients carrying embryos produced by somatic cell nuclear transfer. Anim Reprod Sci 2009;112:172-81. https://doi.org/10.1016/j.anireprosci.2008.04.029
  18. Kim JH, Park JY, Park MR, et al. Developmental arrest of scNT-derived fetuses by disruption of the developing endometrial gland as a result of impaired trophoblast migration and invasiveness. Dev Dyn 2011;240:627-39. https://doi.org/10.1002/dvdy.22568
  19. Lee SY, Park JY, Choi YJ, et al. Comparative proteomic analysis associated with term placental insufficiency in cloned pig. Proteomics 2007;7:1303-15. https://doi.org/10.1002/pmic.200601045
  20. Yoo I, Jung W, Lee S, Cheon Y, Ka H. Inhibitors of apoptosis: expression and regulation in the endometrium during the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Anim Biosci 2022;35:533-43. https://doi.org/10.5713/ab.21.0307
  21. Yoo I, Kim D, Han J, et al. Transcriptomic analysis of interferon-γ-regulated genes in endometrial explants and their possible role in regulating maternal endometrial immunity during the implantation period in pigs, a true epitheliochorial placentation species. Theriogenology 2020;155:114-24. https://doi.org/10.1016/j.theriogenology.2020.05.045
  22. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001;25:402-8. https://doi.org/10.1006/meth.2001.1262
  23. Braissant O, Wahli W. Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development. Endocrinology 1998;139:2748-54. https://doi.org/10.1210/endo.139.6.6049
  24. Choi H, Ignacio RMC, Lee ES, Roby KF, Terranova PF, Son DS. Localization of serum amyloid A3 in the mouse ovary. Immune Netw 2017;17:261-8. https://doi.org/10.4110/in.2017.17.4.261
  25. Ostensen M, Marhaug G, Husby G. Amyloid-related serum protein (SAA) during and after pregnancy in healthy women and women with rheumatic disease. Acta Pathol Microbiol Immunol Scand C 1985;93:1-5. https://doi.org/10.1111/j.1699-0463.1985.tb02913.x
  26. Czopowicz M, Szalus-Jordanow O, Mickiewicz M, et al. Acutephase proteins in pregnant goats: a longitudinal study. J Vet Diagn Invest 2017;29:814-9. https://doi.org/10.1177/1040638717714295
  27. Gaffney PM, Barr B, Rowe JD, et al. Protein profiling of isolated uterine AA amyloidosis causing fetal death in goats. FASEB J 2015;29:911-9. https://doi.org/10.1096/fj.14-256081
  28. Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol 2017;17:469-82. https://doi.org/10.1038/nri.2017.64
  29. Lee S, Jang H, Yoo I, et al. Unique epithelial expression of S100A calcium binding protein A7A in the endometrium at conceptus implantation in pigs. Asian-Australas J Anim Sci 2019;32:1355-62. https://doi.org/10.5713/ajas.18.0920
  30. Urieli-Shoval S, Cohen P, Eisenberg S, Matzner Y. Widespread expression of serum amyloid A in histologically normal human tissues. Predominant localization to the epithelium. J Histochem Cytochem 1998;46:1377-84. https://doi.org/10.1177/002215549804601206
  31. Chapwanya A, Meade KG, Doherty ML, Callanan JJ, O'Farrelly C. Endometrial epithelial cells are potent producers of tracheal antimicrobial peptide and serum amyloid A3 gene expression in response to E. coli stimulation. Vet Immunol Immunopathol 2013;151:157-62. https://doi.org/10.1016/j.vetimm.2012 09.042
  32. Lee S, Yoo I, Han J, Ka H. Antimicrobial peptides cathelicidin, PMAP23, and PMAP37: Expression in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy and regulation by steroid hormones and calcitriol in pigs. Theriogenology 2021;160:1-9. https://doi.org/10.1016/j.theriogenology.2020.10.034
  33. Jang H, Lee S, Yoo I, et al. Calcium-binding proteins S100A8, S100A9, and S100A12: expression and regulation at the maternal-conceptus Interface in pigsdagger. Biol Reprod 2022;106:1098-111. https://doi.org/10.1093/biolre/ioac039