Journal of Animal Science and Technology

Korean Society of Animal Sciences and Technology (한국축산학회)
권호 표지
DOI QR코드

DOI QR Code

A Morphological Study on the Macrophages During Luteolysis in the Pig

돼지 황체에서 황체용해와 대식세포와의 관계

  • 김원식 (충남대학교 의과대학 해부학교실) ;
  • 한승로 (충남대학교 의과대학 해부학교실) ;
  • 손성경 (충남대학교 의과대학 산부인과학교실) ;
  • 박창식 (충남대학교 형질전환복제돼지연구센터) ;
  • 양윤석 (을지대학교 의과대학 산부인과학교실)
  • Published : 2006.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

In addition to the removal of dying or dead lutein cells by phagocytosis in many species, macrophages exert both luteotropic effect during maturation period and luteolytic effect during degenerative period via mediating autocrine/paracrine actions of self-producing cytokines in the corpus luteum. In this experiment, immunohistochemical and transmission electron microscopic (TEM) studies were performed to observe the morphologic changes of luteal macrophages during luteolysis. A small number of macrophages and low immunoreactivity were present at the mature stage. The number of macrophages and immunoreactivity gradually increased along the advance of luteolysis. Two subtypes of macrophages could be observed through TEM observation. One type of macrophage located between the large lutein cells contained no lipid droplets in their cytoplasm at mature stage. The other type of macrophage located near the blood vessels contained many lipid droplets in their cytoplasm during luteolysis. Particularly, no phagocytic macrophages were observed, which suggested the macrophages in the porcine corpus luteum did not involve in the phagocytotic elimination of dying lutein cells.

황체내에서 대식세포는 자신이 분비하는 사이토카인을 통해 황체형성기에는 황체형성세포들의 증식과 성장에 관여하고 황체용해시기에는 황체세포들의 아포토시스와 그들의 제거에 직간접적으로 관여하는 것으로 알려져 있다. 본 실험에서는 돼지에서 최대성숙황체 시기와 황체의 용해에 따른 대식세포의 역할과 작용기전 등을 알아보기 위해 면역조직화학적 및 투과전자현미경적 방법으로 황체의 형태학적 변화를 관찰하였다. 그 결과 돼지에서는 황체용해시에 아포토시스 소체들을 포식하는 대식세포들이 관찰되지 않았고, 최대 황체시기와 황체용해시기에 대식세포들은 미세구조와 그것들이 위치하는 부위가 각기 다른 2가지 아형들이 관찰되었다. 이같은 결과로 볼 때, 돼지에서는 황체용해시 아포토시스 소체들이 대식세포의 포식작용에 의하지 않고 자체 혈관을 통해 제거되는 것으로 보이며, 황체에는 각 시기별로 각기 다른 임무를 띤 아형의 대식세포들이 혈류로부터 들어와 시기특이적으로 작용하는 것으로 추정된다.

Keywords

References

  1. Adams, E. C. and Hertig, A. T. 1969. Studies on the corpus lutenm. I. Observation on the ultrastructure of development and regression of the luteal cells during the menstrual cycle. J. Cell Biol. 41:696715 https://doi.org/10.1083/jcb.41.3.696
  2. Asselin, E., Xiao, C. W ., Wang, Y. F. and Tsang, B. K. 2000. Mammalian follicular development and atresia: role of apoptosis. Biol. Signals Receipt. 9:87-95 https://doi.org/10.1159/000014627
  3. Azmi, T. I. and O'Shea, . D. 1984. Mechanism of deletion of endothelial cells during regression of the corpus luteum. Lab. Invest. 51:206-217
  4. Bacci, M. L., Barazzoni, A. M., Forni, M. and Lalatta Costerbosa, G. 1996. In Situ detection of apoptosis in regressing corpus luteum of pregnant sow: Evidence of an early presence of DNA fragmentation. Dom. Anim. Endocrinol. 13(4):361372 https://doi.org/10.1016/0739-7240(96)00049-5
  5. Bagavandoss, P., Kunkel. S. L., Wiggins, R. C. and Keyes, P. L. 1988. Tumor necrosis factor-$\alpha$ production and localization of macrophages and T lymphocytes in the rabbit corpus luteum. Endocrinology, 122:1185-1187 https://doi.org/10.1210/endo-122-3-1185
  6. Bagavandoss, P., Wiggins, R. C. Kunkel, S. L., Remick, D. G. and Keyes, P. L. 1990. Tumor necrosis factor production and accumulation of inflammatory cells III the corpus luteum of pseudopregnancy and pregnancy in rabbits. Biol. Reprod. 42:367-376 https://doi.org/10.1095/biolreprod42.2.367
  7. Braden. T. D., Gamboni, F. and Niswender, G. D. 1988. Effects of prostaglandin F2$\alpha$-induced luteolysis on the populations of cells in the ovine corpus luteum. Biol. Reprod. 39:245-253 https://doi.org/10.1095/biolreprod39.2.245
  8. Brannstrom. M. B. and Norman. R. J. 1993. Involvement of leukocytes and cytokines in the ovulatory process and corpus luteum function. Hum. Reprod. 8: 1762-1775 https://doi.org/10.1093/oxfordjournals.humrep.a137929
  9. Brannstrom, M., Giesecke, L., Moore, I. C., Van Den Heuvel, C. J. and Robertson, S. A. 1994. Leukocyte subpopulations in the rat corpus luteum during pregnancy and pseudopregnancy. Biol. Reprod. 50: 1161-1167 https://doi.org/10.1095/biolreprod50.5.1161
  10. Bukovsky, A., Caudle, M. R., Keenan, A, Wimalasena, J., Foster, J. S. and van Meter, S. E. 1995. Quantitative evaluation of the cell cycle-related retinoblastoma protein and localization of Thy-l differentiation protein and macrophages during follicular development and atresia, and in human corpora lutea. Biol. Reprod. 52:776-792 https://doi.org/10.1095/biolreprod52.4.776
  11. Bulmer, D. 1964, The histochemistry of ovarian macrophages in the rat. J. Anat. 98:313-319
  12. Chen, H., Marcinkiewicz, J. L., Sancho-Tello, M., Hunt, J. S. and Terranova, P. F. 1993. Tumor necrosis factor-$\kappa$ gene expression In mouse oocytes and follicular cells. Biol Reprod. 48:707-714 https://doi.org/10.1095/biolreprod48.4.707
  13. Clarke, P. G. H. 1990. Developmental cell death: Morphological diversity and multiple mechanisms. Anat. Embryol. 181:195-213
  14. Dijkstra, C. D., Dopp, E. A, Joling, P. and Kraal, G. 1985. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies EDl. ED2 and ED3. Immunol. 54:589599
  15. Duncan, W. C., Rodger, F. E. and Illingworth, P. J. 1998. The human corpus luteum reduction in macrophages during simulated maternal recognition of pregnancy. Hum, Reprod. 13(9):2435-2442 https://doi.org/10.1093/humrep/13.9.2435
  16. Endo, T., Atcn, R. F., Wang, F. and Behrman, H. R. 1993. Coordinate induction and activation of metalloproteinase and ascorbate depletion in structural luteolysis. Endocrinology. 133:690-698 https://doi.org/10.1210/en.133.2.690
  17. Fairchild-Benyo, D. L. and Pate, J. L. 1992. Tumor necrosis factor $\kappa$ alters bovine lutealcell synthetic capacity and viability. Endocrinology. 130:854-860 https://doi.org/10.1210/en.130.2.854
  18. Fukumatsu, Y., Katabuchi. H., Naito, M., Takeya, M., Takahashi, K. and Okamura, H. 1992. Effect of macrophages on proliferation of granulosa cells in the ovary in rats. J. Reprod. Fertil. 96:241-249 https://doi.org/10.1530/jrf.0.0960241
  19. Funayama, Y., Sasano, H. and Suzuki, T, 1996. Cell turnover in normal cycling human ovary. J. Clin. Endocrinol. Metab. 81:828-834 https://doi.org/10.1210/jc.81.2.828
  20. Grossman, C. J. 1984. Regulation of the immune system by sex steroids. Endocrine Reviews. 5:435-455 https://doi.org/10.1210/edrv-5-3-435
  21. Hansel, W., Concannon, P. W. and Lukaszewska, J. H. 1973. Corpora lutea of the large domestic ruminants. Biol. Reprod. 8:222-245 https://doi.org/10.1093/biolreprod/8.2.222
  22. Hehnkc. K. E., Christenson, L. K., Ford, S. P. and Taylor, M. 1994. Macrophage infiltration into the porcine corpus luteum during prostaglandin F2$\kappa$ induced luteolysis. Biol. Reprod. 50:10-15 https://doi.org/10.1095/biolreprod50.1.10
  23. Hulboy, D. L., Rudolph, L. A. and Matrisian, L. M. 1997. Matrix metalloproteinases as mediators of reproductive function. Mol. Hum. Reprod. 3:27-45 https://doi.org/10.1093/molehr/3.1.27
  24. Hume, D. A., Halpin, D., Charlton, H. and Gordon, S. 1984. The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of endocrine organs. Proc. Natl. Acad. Sci. USA. 81:4174
  25. Hurwitz, A., Dushnik, M. and Solomon, H. 1993. Cytokine-mediated regulation of rat ovarian function: interleukin-l stimulates the accumulation of a 92-kilodalton gelatinase. Endocrinology. 132:27092714 https://doi.org/10.1210/en.132.6.2709
  26. Kaipia, A. and Hsueh, A. J. 1997. Regulation of ovarian follicle atresia. Annu. Rev. Physiol. 59: 349-363 https://doi.org/10.1146/annurev.physiol.59.1.349
  27. Kelly, R. W. 1994. Pregnancy maintenance and parturition: the role of prostaglandin in manipulating the immune and inflammatory response. Endocrine Reviews. 15:684-706 https://doi.org/10.1210/edrv-15-5-684
  28. Kerr, J. F. R., Wyllie, A. H. and Currie, A. R. 1972. Apoptosis, a basic biological phenomenon with wider implication in tissue kinetics. Br. J. Cancer. 226:239-247
  29. Kraal, G., Shiamatey-Koolma, R., Hoffer, M., Baker, D. and Scheper, R. 1988. Histochemical identification of guinea-pig macrophages by monoclonal antibody MR-l. Immunology. 65:523-528
  30. Luck, M. R and Zhao, Y. 1995. Structural remodelling of reproductive tissues. J. Endocrinol. 146:191-195 https://doi.org/10.1677/joe.0.1460191
  31. Maylor, M. S., Stamp. G. W. H., Foulkes. W. D., Eccles. D. and Balkwill. F. R. 1993. Tumor necrosis factor and its receptors in human ovarian cancer. J. Clin. Invest. 91 :2194-2206 https://doi.org/10.1172/JCI116446
  32. McCracken, J. A., Glew, M. E. and Scaramuzzi, R. J. 1970. Corpus luteum regression induced by prostaglandin F2$\alpha$. J. Clin. Endocrinol. Metab. 30:544-547 https://doi.org/10.1210/jcem-30-4-544
  33. Mci.rackcn, J. A., Custer, E. E. and Lamsa, J. C. 1999. Luteolysis : A neuroendocrine-mediated event. Physiological Reviews. 79(2):263-324 https://doi.org/10.1152/physrev.1999.79.2.263
  34. McGuire. W. J., Juengel, J. L. and Niswender. G. D. 1994. Protein kinase C second messenger system mediates the antisteroidogenic effects of Prostaglandin F2$\kappa$ in the ovine corpus luteum in vivo. Biol. Reprod. 51:800-806 https://doi.org/10.1095/biolreprod51.4.800
  35. Miyamoto, A., Luetzow, V. H. and Schams, D. 1993. Acute action of prostaglandin F2$\kappa$, E2, and 12 in microdialyzed bovine corpus luteum in vitro. Biol. Reprod. 49:423-430 https://doi.org/10.1095/biolreprod49.2.423
  36. Morales, C, Garcia-Pardo, L., Reymundo, C, Bellido, C, Sanchez-Criado, J. E. and Gaytan, F. 2000. Different patterns of structural luteolysis in the human corpus luteum of menstruation. Hum. Reprod. 15(10):2119-2128 https://doi.org/10.1093/humrep/15.10.2119
  37. Nett, T. M., McClellen, M. C. and Niswender, G. D. 1976. Effects of prostaglandins on the ovine corpus luteum : blood flow, secretion of progesterone and morphology. Biol. Reprod. 15:66-78 https://doi.org/10.1095/biolreprod15.1.66
  38. Niswender, G. D. and Nett, T. M. 1994. Corpus luteum and its control in infraprimate species. In:The Physiology of Reproduction, editied by E. Knobil and JD Neill. New York: Raven, vol. 1, pp., 781-816
  39. Niswender, G. D., Juengel, J. L., Silva, P. J., Rollyson, M. K. and Mcintosh, E. R. 2000. Mechanisms controlling the function and life span of the corpus luteum. Physiological Reviews. 80(1):1-29 https://doi.org/10.1152/physrev.2000.80.1.1
  40. Nothnick, W. B. and Pate, J. L. 1990. Interleukin-I is a potent stimulator of prostaglandin synthesis In bovine luteal cells. Biol, Reprod. 43: 169-173 https://doi.org/10.1095/biolreprod43.2.169
  41. Okuda, K., Uenoyama, Y., Lee, K. W., Sakumoto, R. and Skarzynski, D. J. 1998. Progesterone stimulation by prostaglandin F2$\alpha$ involves protein kinase C pathway in cultured bovine luteal cells. J. Reprod. Dev. 44:79-84 https://doi.org/10.1262/jrd.44.79
  42. O'Shea, J. D., Nightingale, M. G. and Charnley, W. A. 1977. Changes in small blood vessels during cyclical regression in sheep. Biol. Reprod. 17:162177 https://doi.org/10.1095/biolreprod17.2.162
  43. Paavola, L. G. 1977. The corpus luteum of the guinea pig. Fine structure at the time of maximum progesterone secretion and during regression. Am. J. Anat. 150:565-604 https://doi.org/10.1002/aja.1001500406
  44. Paavola, L. G. 1979. The corpus luteum of the guinea pig. IV. Fine structure of macrophages during pregnancy and postpartum luteolysis and the phagocytosis of luteal cells. Am. J. Anat. 154:337-364 https://doi.org/10.1002/aja.1001540304
  45. Parker, C. W. 1991. Neutrophil mechanisms. Am. Rev. Respir. Dis. 143:559-560
  46. Pate, J. L. 1994. Cellular components involved In luteolysis. J. Anim. Sci. 72: 1884-1890
  47. Pate, J. L. and Keyes, P. L. 2001. Immune cells in the corpus luteum : friends or foes? Reproduction. 122:665-676 https://doi.org/10.1530/rep.0.1220665
  48. Pepperell, J. R, Wolcott, C. and Behrman, H. R 1991. Effects of neutrophils in rat luteal cells. Endocrinology. 130:1001-1008
  49. Phariss, B. B., Cornette, J. C. and Gutnecht, G. D. 1970. Vascular control of luteal steroidogenesis. J. Reprod. Fertil. Suppl. 10:97-103
  50. Quatacker, J. R. 1971. Formation of autophagic vacuoles during human corpus luteum involution. Z. Zellforsch. 122:479-487 https://doi.org/10.1007/BF00936082
  51. Roby, K. F. and Terranova, P. F. 1989. Localization of tumor necrosis factor (TNF) in the rat and bovine ovary using immunohistochemistry and cell blot: evidence for granulosa production. In: Hirshfield AN (ed.), Growth Factors and the Ovary. New York. Plenum Publishing Corporation, pp. 273-278
  52. Roby, K. F., Weed, J., Lyles, R. and Terranova, P. F. 1993. Immunological evidence for a human ovarian tumor necrosis factor-alpha. J. Clin. Endocrinol. Metab. 71:1096-1102 https://doi.org/10.1210/jcem-71-5-1096
  53. Rodger, F. E., Fraser, H. M. and Duncan, W. C. 1995. Immunolocalization of bcl-2 in the human corpus luteum. Mol. Hum. Reprod. 1:1566-1570
  54. Sakumoto, R. and Okuda, K 2004. Possible actions of TNF-$\kappa$ in ovarian function. J. Reprod. Dev. 50:39-46 https://doi.org/10.1262/jrd.50.39
  55. Sawyer, H. R., Niswender, K D., Braden, T. D. and Niswender, G. D. 1990. Nuclear changes in ovine luteal cells in response to PGF2$\kappa$. Domest. Anim. Endocrinol. 7:229-238 https://doi.org/10.1016/0739-7240(90)90029-Y
  56. Sawyer, H. R. 1995. Structural and functional properties of the corpus luteum of pregnancy. In Scaranuzzi, R. J., Nancarrow, C. D. and Doberska, C.(eds), Reproduction in Domestic Ruminants III. J. Reprod. Fertil. Dorset. 97: 110
  57. Shakil, T. and Whitehead, S. A. 1994. Inhibitory action of peritoneal macrophages on progesterone secretion from co-cultured rat granulosa cells. Biol. Reprod. 50:1183-1189 https://doi.org/10.1095/biolreprod50.5.1183
  58. Shikone, T., Yamoto, M. and Kokawa, K. 1996. Apoptosis of human corpora lutea during cyclic Luteal regression and early pregnancy. J. Clin. Endocrinol. Metab. 81:2376-2380 https://doi.org/10.1210/jc.81.6.2376
  59. Siiteri, P. K and Stites, D. P. 1982. Immunologic and endocrine interrelationships in pregnancy. Biol. Reprod. 26:1-14 https://doi.org/10.1095/biolreprod26.1.1
  60. Standaert, F. E., Zamora, C. S. and Chew, B. P. 1991. Quantitative and qualitative changes in blood leukocytes in the porcine ovary. Am. J. Reprod. Immunol. 25:163-168 https://doi.org/10.1111/j.1600-0897.1991.tb01088.x
  61. Stouffer, R. L. and Brannian, J. D. 1993. The function and regulation of cell populations composing the corpus luyeum of the ovarian cycle. In Adashi, E. Y. and Leung, P. C. K(eds.), The Ovary. Raven Press, New York, pp. 245249
  62. Tscheshe, H., Fedrowitz, J., Michaelis, J. and Macartney, H. W. 1986. Matrix degrading proteinases from human granulocytes : Type I, II , III collagenase, gelatinase and type IV collagenase. Folia Histochem. Cytobiol. 61:269-273
  63. Wang, L. J., Brannstrom, M., Robertson, S. A. and Norman, R. J. 1992. Tumor necrosis factor alpha in the human ovary: presence in follicular fluid and effects on ell proliferation and prostaglandin production. Fertil. Steril. 58:934-940 https://doi.org/10.1016/S0015-0282(16)55438-7
  64. Yan, Z., Hunter, V., Weed, J., Hutchison, S., Lyles, R. T. and Terranova, P. F. 1993. Tumor necrosis factor-$\alpha$ alters steroidogenesis and stimulates proliferation of human ovarian granulosa cells in vitro. Fertil. Steril. 53:332-338
  65. Yuan, W. and Giudice, L. C. 1997. Programmed cell death in human ovary is a function of a follicle and corpus luteum status. J. Clin. Endocrinol. Metab. 82:3148-3155 https://doi.org/10.1210/jc.82.9.3148
  66. Zhao, Y., Burbach, J. A., Roby, K. F., Terranova, P. F. and Brannian, J. D. 1998. Macrophages are the major source of tumor necrosis factor $\alpha$ in the porcine corpus luteum. Biol. Reprod. 59: 13851391 https://doi.org/10.1095/biolreprod59.6.1385
  67. Zolti. M., Meirom. R., Shemesh, M., Wollach. D., Mashiach. S., Shore, L. and Ben Rafael. Z. 1990. Granulosa cells as a source and target organ for tumor necrosis factor-$\kappa$. FEBS Lett. 261:253-255 https://doi.org/10.1016/0014-5793(90)80565-Z
  68. 김원식, 한승로, 조근자, 김수일, 박창식. 2005. 흰쥐난소에서 황체내 대식세포에 관한 형태학적 연구 : 면역조직화학적 및 투과전자현미경적 연구. 대한해부학회지. 38(3):251-258
  69. 박창식, 한승로. 김수일, 조근자, 김원식. 2004. 돼지난소에서 난포폐쇄시 과립층세포의 아포토시스와 대식세포에 관한 형태학적 연구. 동물자원과학지 46(4):1-14