Animal Bioscience

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
권호 표지
DOI QR코드

DOI QR Code

Matrix metalloproteinases: expression and regulation in the endometrium during the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs

  • Inkyu Yoo (Division of Biological Science and Technology, Yonsei University) ;
  • Soohyung Lee (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 : 2022.12.26
  • Accepted : 2023.03.07
  • Published : 2023.08.01
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Results: Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. Conclusion: These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.

Keywords

Acknowledgement

This study was supported by National Research Foundation grants funded by the Korean Government (NRF-2019R1A2C1004670 to HK and 2020R1A6A3A01098213 to IY), Republic of Korea.

References

  1. Kaloglu C, Onarlioglu B. Extracellular matrix remodelling in rat endometrium during early pregnancy: the role of fibronectin and laminin. Tissue Cell 2010;42:301-6. https://doi.org/10.1016/j.tice.2010.07.004 
  2. Grzechocinska B, Dabrowski FA, Cyganek A, et al. Matrix metalloproteinases-2, -7 and tissue metalloproteinase inhibitor-1 expression in human endometrium. Folia Histochem Cytobiol 2018;56:133-40. https://doi.org/10.5603/FHC.a2018.0017 
  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. Enders AC, Carter AM. What can comparative studies of placental structure tell us?--A review. Placenta 2004;25(Suppl A):S3-9. https://doi.org/10.1016/j.placenta.2004.01.011 
  5. Rahat B, Sharma R, Bagga R, Hamid A, Kaur J. Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases. Reproduction 2016;152:11-22. https://doi.org/10.1530/REP16-0060 
  6. Hamutoglu R, Bulut HE, Kaloglu C, et al. The regulation of trophoblast invasion and decidual reaction by matrix metalloproteinase-2, metalloproteinase-7, and metalloproteinase-9 expressions in the rat endometrium. Reprod Med Biol 2020;19:385-97. https://doi.org/10.1002/rmb2.12342 
  7. Shan B, Li W, Yang SY, Li ZR. Estrogen up-regulates MMP2/9 expression in endometrial epithelial cell via VEGF-ERK1/2 pathway. Asian Pac J Trop Med 2013;6:826-30. https://doi.org/10.1016/S1995-7645(13)60146-7 
  8. Cui N, Hu M, Khalil RA. Biochemical and biological attributes of matrix metalloproteinases. Prog Mol Biol Transl Sci 2017;147:1-73. https://doi.org/10.1016/bs.pmbts.2017.02.005 
  9. Johnson LL, Dyer R, Hupe DJ. Matrix metalloproteinases. Curr Opin Chem Biol 1998;2:466-71. https://doi.org/10.1016/s1367-5931(98)80122-1 
  10. Jiang H, Li H. Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: a systematic review and meta-analysis. BMC Cancer 2021;21:149. https://doi.org/10.1186/s12885-021-07860-2 
  11. Kou L, Jiang X, Lin X, et al. Matrix metalloproteinase inspired therapeutic strategies for bone diseases. Curr Pharm Biotechnol 2021;22:451-67. https://doi.org/10.2174/1389201021666200630140735 
  12. Puente XS, Sanchez LM, Overall CM, Lopez-Otin C. Human and mouse proteases: a comparative genomic approach. Nat Rev Genet 2003;4:544-58. https://doi.org/10.1038/nrg1111 
  13. Abdel-Hamid NM, Abass SA. Matrix metalloproteinase contribution in management of cancer proliferation, metastasis and drug targeting. Mol Biol Rep 2021;48:6525-38. https://doi.org/10.1007/s11033-021-06635-z 
  14. Van Lint P, Libert C. Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol 2007;82:1375-81. https://doi.org/10.1189/jlb.0607338 
  15. Yan C, Boyd DD. Regulation of matrix metalloproteinase gene expression. J Cell Physiol 2007;211:19-26. https://doi.org/10.1002/jcp.20948 
  16. Goffin F, Munaut C, Frankenne F, et al. Expression pattern of metalloproteinases and tissue inhibitors of matrix-metalloproteinases in cycling human endometrium. Biol Reprod 2003;69:976-84. https://doi.org/10.1095/biolreprod.103.015933 
  17. Staun-Ram E, Shalev E. Human trophoblast function during the implantation process. Reprod Biol Endocrinol 2005;3:56. https://doi.org/10.1186/1477-7827-3-56 
  18. Ghosh D, Najwa AR, Khan MA, Sengupta J. IGF2, IGF binding protein 1, and matrix metalloproteinases 2 and 9 in implantation-stage endometrium following immunoneutralization of vascular endothelial growth factor in the rhesus monkey. Reproduction 2011;141:501-9. https://doi.org/10.1530/REP10-0475 
  19. Samborski A, Graf A, Krebs S, et al. Transcriptome changes in the porcine endometrium during the preattachment phase. Biol Reprod 2013;89:134. https://doi.org/10.1095/biolreprod.113.112177 
  20. Zeng S, Ulbrich SE, Bauersachs S. Spatial organization of endometrial gene expression at the onset of embryo attachment in pigs. BMC Genomics 2019;20:895. https://doi.org/10.1186/s12864-019-6264-2 
  21. Seo H, Kim M, Choi Y, Lee CK, Ka H. Analysis of lysophosphatidic acid (LPA) receptor and LPA-induced endometrial prostaglandin-endoperoxide synthase 2 expression in the porcine uterus. Endocrinology 2008;149:6166-75. https://doi.org/10.1210/en.2008-0354 
  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. Yoo I, Kim D, Han J, et al. Transcriptomic analysis of interferon-gamma-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 
  24. 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 
  25. 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 
  26. Snoek-van Beurden PAM, Von den Hoff JW. Zymographic techniques for the analysis of matrix metalloproteinases and their inhibitors. Biotechniques 2005;38:73-83. https://doi.org/10.2144/05381RV01 
  27. Goldman S, Shalev E. Progesterone receptor isoforms profile, modulate matrix metalloproteinase 2 expression in the decidua. Am J Obstet Gynecol 2007;197:604 e1-8. https://doi.org/10.1016/j.ajog.2007.04.011 
  28. Skrzypczak J, Wirstlein P, Mikolajczyk M, Ludwikowski G, Zak T. TGF superfamily and MMP2, MMP9, TIMP1 genes expression in the endometrium of women with impaired reproduction. Folia Histochem Cytobiol 2007;45(Suppl 1):S143-8. 
  29. Ulbrich SE, Meyer SU, Zitta K, et al. Bovine endometrial metallopeptidases MMP14 and MMP2 and the metallopeptidase inhibitor TIMP2 participate in maternal preparation of pregnancy. Mol Cell Endocrinol 2011;332:48-57. https://doi.org/10.1016/j.mce.2010.09.009 
  30. Kaeoket K, Persson E, Dalin AM. The sow endometrium at different stages of the oestrous cycle: studies on morphological changes and infiltration by cells of the immune system. Anim Reprod Sci 2001;65:95-114. https://doi.org/10.1016/s0378-4320(00)00211-6 
  31. Enders AC, Blankenship TN. Comparative placental structure. Adv Drug Deliv Rev 1999;38:3-15. https://doi.org/10.1016/s0169-409x(99)00003-4 
  32. Velez C, Clauzure M, Williamson D, et al. IL-1beta, IL-2 and IL-4 concentration during porcine gestation. Theriogenology 2019;128:133-9. https://doi.org/10.1016/j.theriogenology.2019.01.017 
  33. Kaczynski P, Kowalewski MP, Waclawik A. Prostaglandin F2alpha promotes angiogenesis and embryo-maternal interactions during implantation. Reproduction 2016;151:539-52. https://doi.org/10.1530/REP-15-0496 
  34. Choi WS, Jeon OH, Kim DS. CD40 ligand shedding is regulated by interaction between matrix metalloproteinase-2 and platelet integrin alpha(IIb)beta(3). J Thromb Haemost 2010;8:1364-71. https://doi.org/10.1111/j.1538-7836.2010.03837.x 
  35. Secchiero P, Gonelli A, Corallini F, Ceconi C, Ferrari R, Zauli G. Metalloproteinase 2 cleaves in vitro recombinant TRAIL: potential implications for the decreased serum levels of TRAIL after acute myocardial infarction. Atherosclerosis 2010;211:333-6. https://doi.org/10.1016/j.atherosclerosis.2010.02.024 
  36. Yoo I, Kye YC, Han J, et al. Uterine epithelial expression of the tumor necrosis factor superfamily: a strategy for immune privilege during pregnancy in a true epitheliochorial placentation species. Biol Reprod 2020;102:828-42. https://doi.org/10.1093/biolre/ioz233