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Effects of Progesterone and 17β-Estradiol under Presence or Absence of FBS on Plasminogen Activators Activity in Porcine Uterine Epithelial Cells

  • Hwangbo, Yong (College of Animal Life Sciences, Kangwon National University) ;
  • Lee, Mi-Rim (College of Animal Life Sciences, Kangwon National University) ;
  • Cheong, Hee-Tae (College of Veterinary Medicine, Kangwon National University) ;
  • Yang, Boo-Keun (College of Animal Life Sciences, Kangwon National University) ;
  • Park, Choon-Keun (College of Animal Life Sciences, Kangwon National University)
  • 투고 : 2018.10.05
  • 심사 : 2018.11.10
  • 발행 : 2018.12.31

초록

The present study was conducted to investigate the regulatory mechanism of plasminogen activators (PAs) activation by $17{\beta}$-estradiol ($E_2$) and progesterone ($P_4$) in porcine uterine epithelial cells (pUECs). pUECs were collected from porcine uterine horn and cultured at 80% confluence. Then, 0.1% (v/v) DMSO, 20 ng/mL $E_2$, and $P_4$ with or without fetal bovine serum (FBS) treated to cultured cells for 24 hours. The supernatants were used for measurement of PAs activity and expression of urokinase-type PA (uPA), tissue-type PA (tPA), uPA specific receptor (uPAR), and type-1 PA inhibitor (PAI-1) mRNA were analyzed by real-time PCR. The expression of PAs-related genes was not affect by steroid hormones in both of serum treatment groups. However, PAs activity was increased by treatment of $E_2$ compared to 0.1% DMSO treatment in serum-free group (p<0.05). Then, $E_2$ and $P_4$ were diluted with 0.002% (v/v) DMSO for reduction of its effect and treated to cultured cells without FBS. Only tPA mRNA was significantly increased by $E_2$ treatment (p<0.05). PAs activity was enhanced in $E_2$ treated group compared to control groups (p<0.05). These results indicate that serum-free condition is more proper to evaluate effect of steroid hormones and activation of PAs in pUECs was mainly regulated by estrogen. These regulation of PAs activation may be associated with uterine remodeling during pre-ovulatory phase in pigs, however, further studies are needed to investigate precise regulatory mechanism.

키워드

참고문헌

  1. Ahn SH, Cheong HT, Yang BK, Kim DY, Park CK (2009) Relationship between plasminogen activity and plasminogen inhibitor during the culture of porcine oviduct epithelial cells. Reprod Dev Biol 33:203-209.
  2. Baker VL, Draper M, Paul S, Allerheiligen S, Glant M, Shifren J, Jaffe RB (1998) Reproductive endocrine and endometrial effects of raloxifene hydrochloride, a selective estrogen receptor modulator, in women with regular menstrual cycles. J Clin Endocr Metab 83:6-13.
  3. Bazer FW, Burghardt RC, Johnson GA, Spencer TE, Wu G (2008) Interferons and progesterone for establishment and maintenance of pregnancy: Interactions among novel cell signaling pathways. Reprod Biol 8:179-211. https://doi.org/10.1016/S1642-431X(12)60012-6
  4. Bazer FW, Johnson GA (2014) Pig blastocyst-uterine interactions. Differentiation 87:52-65. https://doi.org/10.1016/j.diff.2013.11.005
  5. Beers WH (1975) Follicular plasminogen and plasminogen activator and the effect of plasmin on ovarian follicle wall. Cell 6:379-386. https://doi.org/10.1016/0092-8674(75)90187-7
  6. Casslen B, Astedt B (1983) Occurrence of both urokinase and tissue plasminogen activator in the human endometrium. Contraception 28:553-564. https://doi.org/10.1016/0010-7824(83)90106-3
  7. Cheon YP (2007) Altering of collagens in early pregnant mouse uterus. Dev Reprod 11:1-11.
  8. Cheon YP, Lee DM, Chun TH, Lee KH, Choi IH (2009) Androgen in the uterus: A compensator of estrogen and progesterone. Dev Reprod 13:133-143.
  9. Coy P, Jimenez-Movilla M, Garcia-Vazquez FA, Mondejar I, Grullon L, Romar R (2012) Oocytes use the plasminogen-plasmin system to remove supernumerary spermatozoa. Hum Reprod 27:1985-1993. https://doi.org/10.1093/humrep/des146
  10. de Boer JP, Creasey AA, Chang A, Abbink JJ, Roem D, Eerenberg AJ, Hack CE, Taylor FB Jr (1993) Alpha-2-macroglobulin functions as an inhibitor of fibrinolytic, clotting, and neutrophilic proteinases in sepsis: studies using a baboon model. Infect Immun 61:5035-5043.
  11. Demir R, Yaba A, Huppertz B (2010) Vasculogenesis and angiogenesis in the endometrium during menstrual cycle and implantation. Acta Histochem 112:203-214. https://doi.org/10.1016/j.acthis.2009.04.004
  12. Ebisch IMW, Thomas CMG, Wetzels AMM, Willemsen WNP, Sweep FCGJ, Steegers-Theunissen RPM (2008) Review of the role of the plasminogen activators system and vascular endothelial growth factor in subfertility. Fertil Steril 90:2340-2350. https://doi.org/10.1016/j.fertnstert.2007.10.026
  13. Elangovan S, Ramachandran S, Venkatesan N, Ananth S, Gnana-Prakasam JP, Martin PM, Browning DD, Schoenlein PV, Prasad PD, Ganapathy V, Thangaraju M (2011) SIRT1 is essential for oncogenic signaling by estrogen/estrogen receptor $\alpha$ in breast cancer. Cancer Res 71: 6654-6664. https://doi.org/10.1158/0008-5472.CAN-11-1446
  14. Fazleabas AT, Bazer FW, Roberts RM (1982) Purification and properties of a progesterone-induced plasmin/trypsin inhibitor from uterine secretions of pigs and its immunocytochemical localization in the pregnant uterus. J Biol Chem 257:6886-6897.
  15. Finlay TH, Katz J, Kirsch L, Levitz M, Nathoo SA, Seiler S (1983) Estrogen-stimulated uptake of plasminogen by the mouse uterus. Endocrinology 112:856-861. https://doi.org/10.1210/endo-112-3-856
  16. Franczak A, Wojciechowicz B, Kotwica G (2013) Transcriptomic analysis of the porcine endometrium during early pregnancy and the estrous cycle. Reprod Biol 13: 229-237. https://doi.org/10.1016/j.repbio.2013.07.001
  17. Gray CA, Bartol FF, Tarleton BJ, Wiley AA, Johnson GA, Bazer FW, Spencer TE (2001) Developmental biology of uterine glands. Biol Reprod 65:1311-1323. https://doi.org/10.1095/biolreprod65.5.1311
  18. Hwangbo Y, Lee SH, Cha HJ, Song EJ, Lee ST, Lee ES, Cheong HT, Yang BK, Park CK (2013) Expression of plasminogen activators in uterine epithelial cells of preovulatory phase in pigs. J Embryo Transf 28:257-263. https://doi.org/10.12750/JET.2013.28.3.257
  19. Ka H, Jaeger LA, Johnson GA, Spencer TE, Bazer FW (2001) Keratinocyte growth factor is up-regulated by estrogen in the porcine uterine endometrium and functions in trophectoderm cell proliferation and differentiation. Endocrinology 142:2303-2310. https://doi.org/10.1210/endo.142.6.8194
  20. Kim KH, Lee YS, Gu HN, Yang BK, Cheong HT, Park CK (2011) Changes in plasminogen activity in uterus tissue during the estrous cycle in the pigs. Reprod Dev Biol 35:463-468.
  21. Kobayashi T, Matsuda Y, Park JY, Hara I, Kaneko S, Fujimoto Y, Nozawa S, Akihama S (1992) Trypsin-like arginine amidases including plasminogen and plasmin in human seminal plasma by affinity adsorption and elution. Arch Androl 28:165-170. https://doi.org/10.3109/01485019208987694
  22. Kouba AJ, Burkhardt BR, Alvarez IM, Goodenow MM, Buhi WC (2000) Oviductal plasminogen activator inhibitor-1 (PAI-1): mRNA, protein, and hormonal regulation during the estrous cycle and early pregnancy in the pig. Mol Reprod Dev 56:378-386. https://doi.org/10.1002/1098-2795(200007)56:3<378::AID-MRD8>3.0.CO;2-B
  23. Krania F, Dovolou E, Rekkas CA, Theodosiadou EK, Pappas I, Amiridis GS (2015) Effects of addition of tissuetype plasminogen activator in in vitro fertilization medium on bovine embryo development and quality. Reprod Domest Anim 50:112-120. https://doi.org/10.1111/rda.12456
  24. Lai MD, Lee LR, Cheng KS, Wing LYC (2000) Expression of proliferating cell nuclear antigen in luminal epithelium during the growth and regression of rat uterus. J Endocrinol 166:87-93. https://doi.org/10.1677/joe.0.1660087
  25. Martin O, Arias F (1982) Plasminogen activator production by trophoblast cells in vitro: Effect of steroid hormones and protein synthesis inhibitors. Am J Obstet Gynecol 142:402-409. https://doi.org/10.1016/S0002-9378(16)32380-8
  26. McCracken JA (1980) Hormone receptor control of prostaglandin F2 alpha secretion by the ovine uterus. Adv Prostaglandin Thromboxane Res 8:1329-1344.
  27. Menshikov M, Plekhanova O, Cai H, Chalupsky K, Parfyonova Y, Bashtrikov P, Tkachuk V, Berk BC (2006) Urokinase plasminogen activator stimulates vascular smooth muscle cell proliferation via redox-dependent pathways. Arter Thromb Vasc Biol 26:801-807. https://doi.org/10.1161/01.ATV.0000207277.27432.15
  28. Mullins DE, Bazer FW, Roberts RM (1980) Secretion of a progesterone-induced inhibitor of plasminogen activator by the porcine uterus. Cell 20:865-872. https://doi.org/10.1016/0092-8674(80)90333-5
  29. Noguchi M, Yoshioka K, Itoh S, Suzuki C, Arai S, Wada Y, Hasegawa Y, Kaneko H (2010) Peripheral concentrations of inhibin A, ovarian steroids, and gonadotropins associated with follicular development throughout the estrous cycle of the sow. Reproduction 139:153-161. https://doi.org/10.1530/REP-09-0018
  30. Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson U (1998) Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci USA 95:11709-11714. https://doi.org/10.1073/pnas.95.20.11709
  31. Ploplis VA, French EL, Carmeliet P, Collen D, Plow EF (1998) Plasminogen deficiency differentially affects recruitment of inflammatory cell populations in mice. Blood 91:2005-2009. https://doi.org/10.1182/blood.V91.6.2005
  32. Sappino AP, Huarte J, Belin D, Vassalli JD (1989) Plasminogen activators in tissue remodeling and invasion: mRNA localization in mouse ovaries and implanting embryos. J Cell Biol 109:2471-2479. https://doi.org/10.1083/jcb.109.5.2471
  33. Schatz F, Aigner S, Papp C, Toth-Pal E, Hausknecht V, Lockwood CJ (1995) Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1. J Clin Endocrinol Metab 80:2504-2510.
  34. Schatz F, Lockwood CJ (1993) Progestin regulation of plasminogen activator inhibitor type 1 in primary cultures of endometrial stromal and decidual cells. J Clin Endocrinol Metab 77:621-625.
  35. Spencer TE, Bazer FW (2002) Biology of progesterone action during pregnancy recognition and maintenance of pregnancy. Front Biosci 7:1879-1898. https://doi.org/10.2741/A886
  36. Spencer TE, Becker WC, George P, Mirando MA, Ogle TF, Bazer FW (1995) Ovine interferon-tau regulates expression of endometrial receptors for estrogen and oxytocin but not progesterone. Biol Reprod 53:732-745. https://doi.org/10.1095/biolreprod53.3.732
  37. Spencer TE, Johnson GA, Burghardt RC, Bazer FW (2004) Progesterone and placental hormone actions on the uterus: Insights from domestic animals. Biol Reprod 71:2-10. https://doi.org/10.1095/biolreprod.103.024133
  38. Stroband HWJ, Taverne, N, Langenfeld K, Barends PMG (1986) The ultrastructure of the uterine epithelium of the pig during the estrous cycle and early pregnancy. Cell Tissue Res 246:81-89.
  39. Tanikawa M, Kim TS, Okuda K, Ryoo ZY, Park SB, Shin JH, Park CK, Lee DS (2009) Cell-type specificity of interleukins $1{\alpha}$ and $1{\beta}$ on prostaglandin and plasminogen activator production in bovine endometrial cell. Anim Reprod Sci 114:32-42. https://doi.org/10.1016/j.anireprosci.2008.09.003
  40. White FJ, Ross JW, Joyce MM, Geisert RD, Burghardt RC, Johnson GA (2005) Steroid regulation of cell specific secreted phosphoprotein 1 (osteopontin) expression in the pregnant porcine uterus. Biol Reprod 73:1294-1301. https://doi.org/10.1095/biolreprod.105.045153
  41. Yan W, Chen J, Wiley AA, Crean-Harris BD, Bartol FF, Bagnell CA (2008) Relaxin (RLX) and estrogen affect estrogen receptor $\alpha$, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix. Reproduction 135:705-712. https://doi.org/10.1530/REP-08-0014