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Journal of Assisted Reproduction and Genetics

, Volume 16, Issue 10, pp 512–519 | Cite as

The Role of Apoptosis in Normal and Abnormal Embryonic Development

  • Alexander Brill
  • Arkady Torchinsky
  • Howard Carp
  • Vladimir Toder
Article

Abstract

Programmed cell death or apoptosis is a widespread biological phenomenon. Apoptosis is characterized by typical cell features such as membrane blebbing, chromatin condensation, and DNA fragmentation. It involves a number of membrane receptors (e.g., Fas, TNFR) and a cascade of signal transduction steps resulting in the activation of a number of cysteine proteases known as caspases. Disordered apoptosis may lead to carcinogenesis and participates in the pathogenesis of Alzheimer disease, Parkinson disease, or AIDS. Programmed cell death plays an important role in the processes of gamete maturation as well as in embryo development, contributing to the appropriate formation of various organs and structures. Apoptosis is one of the mechanisms of action of various cytotoxic agents and teratogens. Teratogen-induced excessive death of embryonic cells is undoubtedly one of the most important events preceding the occurrence of structural abnormalities, regardless of their nature. Therefore understanding the mechanisms involved in physiological as well as in disturbed or dysregulated apoptosis may lead to the development of new methods of preventive treatment of various developmental abnormalities. The present review summarizes data on the mechanisms of programmed cell death and concentrates on apoptosis involved in normal or disturbed gametogenesis and in normal and abnormal embryonic development.

apoptosis gametogenesis embryogenesis maldevelopment 

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REFERENCES

  1. 1.
    Sadler TW, Hanter ES: Principles of abnormal development. Past, present and future. In Development Toxicology, CA Kimmel, J. Buelke-Sam (eds). New York, Raven Press, 1994, pp. 53-63Google Scholar
  2. 2.
    Richburg JH: Environmental testicular toxicity & germ cell apoptosis. Bethesda, MD, Crisp Data base, National Institutes of Health, 1999Google Scholar
  3. 3.
    Bodey B, Bodey B Jr, Kaiser HE: Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions. In Vivo 1998;12:123-133Google Scholar
  4. 4.
    Collins JA, Schandi CA, Young KK, Vesely J, Willingham MC: Major DNA fragmentation is a late event in apoptosis. J Histochem Cytochem 1997;45:923-934Google Scholar
  5. 5.
    Thornberry NA, Lazebnik Y: Caspases: enemies within. Science 1998;281:1312-1316Google Scholar
  6. 6.
    Ashkenazi A, Dixit VM: Death receptors: signaling and modulation. Science 1998;281:1305-1308Google Scholar
  7. 7.
    Peter ME, Krammer PH: Mechanisms of CD95 (APO-1/FAS)-mediated apoptosis. Curr Opin Immunol 1998;10:545-551Google Scholar
  8. 8.
    Fuchs EJ, McKenna KA, Bedi A: P53-dependent DNA damage-induced apoptosis requires FAS/APO-1-independent activation of CPP32beta. Cancer Res 1997;57:2550-2554Google Scholar
  9. 9.
    Evan G, Littlewood T: A matter of life and cell death. Science 1998;281:1317-1322Google Scholar
  10. 10.
    King KL, Cidlowski JA: Cell cycle regulation and apoptosis. Annu Rev Physiol 1998;60:601-617Google Scholar
  11. 11.
    Janicke RU, Sprengart ML, Wati MR, Porter AG: Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 1998;273:9357-9360Google Scholar
  12. 12.
    Adams JM, Cory S: The Bcl-2 protein family: arbitres of cell survival. Science, 1998;281:1322-1326Google Scholar
  13. 13.
    Sadoul R: BCL-2 family members in the development and degenerative pathologies of the nervous system. Cell Death Diff 1998;5:805-815Google Scholar
  14. 14.
    Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, Su MS, Rakic P, Flavell RA: Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 1998;94:325-337Google Scholar
  15. 15.
    Woo M, Hakem R, Soengas MS, Duncan GS, Shahinian A, Kagi D, Hakem A, McCurrach M, Khoo W, Kaufman SA, Senaldi G, Howard T, Lowe SW, Mak TW: Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev 1998;12:806-819Google Scholar
  16. 16.
    Blanco-Rodriguez J, Martinez-Garcia C: Apoptosis pattern elicited by several apoptogenic agents on the seminiferous epithelium of the adult rat testis. J Androl 1998;19:487-497Google Scholar
  17. 17.
    Larsen WJ: Human Embryology. Singapore, Churchill Livingstone, 1993Google Scholar
  18. 18.
    De Pol A, Vaccina F, Forabosco A, Cavazzuti E, Marzona L: Apoptosis of germ cells during human prenatal oogenesis. Hum Reprod 1997;12:2235-2241Google Scholar
  19. 19.
    De Pol A, Marzona L, Vaccina F, Negro R, Sena P, Forabosco A: Apoptosis in different stages of human oogenesis. Anticancer Res 1998;18:3457-3461Google Scholar
  20. 20.
    Tesarik J, Guido M, Mendoza C, Greco E: Human spermatogenesis in vitro: Respective effects of follicle-stimulating hormone and testosterone on meiosis, spermiogenesis, and Sertoli cell apoptosis. J Clin Endocrinol Metab 1998;83:4467-4473Google Scholar
  21. 21.
    Pentikainen V, Erkkila K, Dunkel L: Fas regulates germ cell apoptosis in the human testis in vitro. Am J Physiol 1999;276(2, Pt 1):E310-E316Google Scholar
  22. 22.
    Lee J, Richburg JH, Younkin SC, Boekelheide K: The Fas system is a key regulator of germ cell apoptosis in the testis. Endocrinology 1997;138:2081-2088Google Scholar
  23. 23.
    Sugihara A, Saiki S, Tsuji M, Tsujimura T, Nakata Y, Kubota A, Kotake T, Terada N: Expression of Fas and Fas ligand in the testes and testicular germ cell tumors: an immunohistochemical study. Anticancer Res 1997;17:3861-2865Google Scholar
  24. 24.
    Ogi S, Tanji N, Yokoyama M, Takeuchi M, Terada N: Involvement of Fas in the apoptosis of mouse germ cells induced by experimental cryptorchidism. Urol Res 1998;26:17-21Google Scholar
  25. 25.
    Leo CP, Hsu SY, McGee EA, Salanova M, Hsueh AJ: DEFT, a novel death effector domain-containing molecule predominantly expressed in testicular germ cells. Endocrinology 1998;139:4839-4848Google Scholar
  26. 26.
    Schwartz D, Goldfinger N, Rotter V: Expression of p53 protein in spermatogenesis is confined to the tetraploid pachytene primary spermatocytes. Oncogene 1993;8:1487-1494Google Scholar
  27. 27.
    Almon E, Goldfinger N, Kapon A, Schwartz D, Levine A.J, Rotter V: Testicular tissue-specific expression of the p53 supressor gene. Dev Biol 1993;156:107-116Google Scholar
  28. 28.
    Sjoblom T, Lahdetie J: Expression of p53 in normal and gamma-irradiated rat testis suggests a role for p53 in a meiotic recombination and repair. Oncogene 1996;12:2499-2505Google Scholar
  29. 29.
    Yin Y, Stahl BC, DeWolf WC, Morgentaler A: p53-mediated germ cell quality control in spermatogenesis. Dev Biol 1998;204:165-171Google Scholar
  30. 30.
    De Rooij DG: Stem cells in the testis. Int J Exp Pathol 1998;79:67-80Google Scholar
  31. 31.
    Rodriguez I, Ody C, Araki K, Garcia I, Vassalli P: An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis. EMBO 1997;16:2262-2270Google Scholar
  32. 32.
    Print CG, Loveland KL, Gibson L, Meehan T, Stylianou A, Wreford N, de Kretser D, Metcalf D, Kontgen F, Adams JM, Cory S: Apoptosis regulator bcl-w is essential for spermatogenesis but appears otherwise redundant. Proc Natl Acad Sci USA 1998;95:12424-12431Google Scholar
  33. 33.
    Hasegawa M, Zhang Y, Niibe H, Terry NH, Meistrich ML: Resistance of differentiating spermatogonia to radiation-induced apoptosis and loss in p53-deficient mice. Radiat Res 1998;149(3):263-270Google Scholar
  34. 34.
    Oliver RT: Germ cell cancer of the testis. Curr Opin Oncol 1998;10(3):266-272Google Scholar
  35. 35.
    Xu JP, Li X, Mori E, Sato E, Saito S, Guo MW, Mori T: Expression of Fas-Fas ligand system associated with atresia in murine ovary. Zygote 1997;5(4):321-327Google Scholar
  36. 36.
    Ogi S, Tanji N, Yokoyama M, Takeuchi M, Terada N: Involvement of Fas in the apoptosis of mouse germ cells induced by experimental cryptorchidism. Urol Res 1998;26(1):17-21Google Scholar
  37. 37.
    Arriola EL, Rodriguez-Lopez AM, Hickman JA, Chresta CM: Bcl-2 overexpression results in reciprocal downregulation of Bcl-X(L) and sensitizes human testicular germ cell tumours to chemotherapy-induced apoptosis. Oncogene 1999;18(7):1457-1464Google Scholar
  38. 38.
    Woolveridge I, de Boer-Brouwer M, Taylor MF, Teerds KJ, Wu FC, Morris ID: Apoptosis in the rat spermatogenic epithelium following androgen withdrawal: Changes in apoptosis-related genes. Biol Reprod 1999;60(2):461-470Google Scholar
  39. 39.
    Hardy K: Cell death in mammalian blastocyst. Mol Hum Reprod 1997;3:919-925Google Scholar
  40. 40.
    Kumazawa T, Inouye M, Hayasaka I, Yamamura H, Murata Y: Difference in sensitivity of inner cell mass and trophectoderm to X-irradiation in mouse blastocysts. Teratology 1998;57:146-151Google Scholar
  41. 41.
    Brison DR, Schultz RM: Apoptosis during mouse blastocyst formation: Evidence for a role for survival factors including transforming growth factor alpha. Biol Reprod 1997;56:1088-1096Google Scholar
  42. 42.
    Runic R, Lockwood CJ, LaChapelle L, Dipasquale B, Demopoulos RI, Kumar A, Guller S: Apoptosis and Fas expression in human fetal membranes. J Clin Endocrinol Metab 1998;83:660-666Google Scholar
  43. 43.
    Wiley LM, Wu JX, Harari I, Adamson ED: Epidermal growth factor receptor mRNA and protein increase after the four-cell preimplantation stage in murine development. Dev Biol 1992;149:247-260Google Scholar
  44. 44.
    Nelson DM: Apoptotic changes occur in syncytiotrophoblast of human placental villi where fibrin type fibrinoid is deposited at discontinuities in the villous trophoblast. Placenta 1996;17:387-391Google Scholar
  45. 45.
    Uckan D, Steele A, Cherry, Wang BY, Chamizo W, Koutsonikolis A, Gilbert-Barness E, Good RA: Trophoblasts express Fas ligand: A proposed mechanism for immune privilege in placenta and maternal invasion. Mol Hum Reprod 1997;3:655-662Google Scholar
  46. 46.
    Jacobson MD, Weil M, Raff MC: Programmed cell death in animal development. Cell 1997;88:347-354Google Scholar
  47. 47.
    Narayanan V: Apoptosis in development and disease of the nervous system. 1. Naturally occurring cell death in the developing nervous system. Pediatr Neurol 1997;16:9-13Google Scholar
  48. 48.
    Mori C, Nakamura N, Kimura S, Irie H, Takigawa T, Shiota K: Programmed cell death in the interdigital tissue of the fetal mouse limb is apoptosis with DNA fragmentation. Anat Rec 1995;242:103-110Google Scholar
  49. 49.
    Zakeri ZF, Ahuja HS: Cell death/apoptosis: Normal, chemically induced and teratogenic effect. Mutat Res 1997;396:149-161Google Scholar
  50. 50.
    Hurle JM, Ros MA, Climent V, Garcia-Martinez V: Morphology and significance of programmed cell death in the developing limb bud of the vertebrate embryo. Microsc Res Tech 1996;34:236-246Google Scholar
  51. 51.
    Lee DM, Osathanondh R, Yeh J: Localization of Bcl-2 in the human fetal mullerian tract. Fertil Steril 1998;70:135-140Google Scholar
  52. 52.
    Kavlock RJ, Daston GP: Introduction. In Drug Toxicity in Embryonic Development, RJ Kavlock, GP Daston (eds). Berlin/Heidelberg, Springer-Verlag, 1997, pp 1-11Google Scholar
  53. 53.
    Scott WJ: Cell death and reduced proliferative rate. In Handbook of Teratology, Vol. 2, JG Wilson, FC Fraser (eds). New York/London, Plenum Press, 1977, pp 81-98Google Scholar
  54. 54.
    Edwards MJ, Walsh DA, Li Z: Hyperthermia, teratogenesis and the heat shock response in mammalian embryos in culture. Int J Dev Biol 1997;41:345-358Google Scholar
  55. 55.
    Shepard TH: Catalog of Teratogenic Agents. Baltimore/London, The Johns Hopkins University Press, 1992Google Scholar
  56. 56.
    Mirkes PE, Cornel LM, Park HW, Cunnigham ML: Induction of thermotolerance in early postimplantation rat embryos is associated with increased resistance to hyperthermia-induced apoptosis. Teratology 1997;56:210-219Google Scholar
  57. 57.
    Yitzhakie D, Torchinsky A, Savion S, Toder V: Maternal immunopotentiation affects the teratogenic response to hyperthermia. J Reprod Immunol 1999 (in press)Google Scholar
  58. 58.
    Siles E, Villalobos M, Jones L, Guerrero R, Eady JJ, Valenzuela MT, Nunez MI, McMillan TJ, Ruiz de Almodovar JM: Apoptosis after gamma irradiation. Is it an important cell death modality? Br J Cancer 1998;78:1594-1599Google Scholar
  59. 59.
    Torchinsky A, Fein A and Toder V: Immunoteratology: I. MHC involvement in the embryo response to teratogens in mice. Am J Reprod Immunol 1995;34:288-298Google Scholar
  60. 60.
    Zile MH: Vitamin A and embryonic development: An overview. J Nutr 1998;128:455S-458SGoogle Scholar
  61. 61.
    Rogers MB: Life-and-death decision influenced by retinoids. Curr Topics Dev Biol 1997;35:1-46Google Scholar
  62. 62.
    Phelan SA, Ito M, Loeken MR: Neural tube defects in embryos of diabetic mice: role of the Pax-3 gene and apoptosis. Diabetes 1997;46:1189-1197Google Scholar
  63. 63.
    Moley KH, Chi MM, Knudson CM, Korsmeyer SJ, Mueckler MM: Hyperglycemia induces apoptosis in pre-implantation embryos through cell death effector pathways. Nat Med 1998;4:1421-1424Google Scholar
  64. 64.
    Forsberg H, Eriksson UJ, Welsh N: Apoptosis in embryos of diabetic rats. Pharmacol Toxicol 1998;83:104-111Google Scholar
  65. 65.
    Wilson JG: Current status of teratology-general principles and mechanisms derived from animal studies. In Handbook of Teratology, Vol 1, JG Wilson, FC Fraser (eds). New York/London, Plenum Press, 1977, pp 47-74Google Scholar
  66. 66.
    Torchinsky A, Savion S, Gorivodsky M, Shepshelovich J, Zaslavsky Z, Fein A. Toder V: Cyclophosphamide-induced teratogenesis in ICR mice: The role of apoptosis. Teratogen Mutagen Carcinogen 1995;15:179-190Google Scholar
  67. 67.
    Nomura T, Hata S, Kusafuka T: Suppression of developmental anomalies by maternal macrophages in mice. J Exp Med 1990;172:1325-1330Google Scholar
  68. 68.
    Baines MG, Duglos AJ, deFougerolles AR, and Gendron RL: Immunological prevention of spontaneous early embryo resorption is mediated by non-specific immunostimulation. Am J Reprod Immunol 1996;35:34-42Google Scholar
  69. 69.
    Clark DA, Banwatt D and Chaouat G: Stress-triggered abortion in mice is prevented by alloimmunization. Am J Reprod Immunol 1993;29:141-147Google Scholar
  70. 70.
    Torchinsky A, Toder V, Savion S, Shepshelovich J, Orenstein H and Fein A: Immunopotentiation increases the resistance of mouse embryos to diabetes-induced teratogenic effect. Diabetologia 1997;40:635-640Google Scholar
  71. 71.
    Toder V, Savion S, Gorivodsky M, Shepshelovich J, Torchinsky A: Teratogen-induced apoptosis may be affected by immunopotentiation. J Reprod Immunol 1996;30:173-185Google Scholar
  72. 72.
    Ivnitsky I, Torchinsky A, Gorivodsky M, Zemlyak I, Orenstein H, Savion S, Shepshelovich J, Carp H, Fein A, Toder V: TNF-α expression in embryos exposed to a teratogen. Am J Reprod Immunol 1998;40:431-440Google Scholar
  73. 73.
    Gorivodsky M, Zemliak I, Orenstein H, Savion S, Fein A, Torchinsky A, Toder V: Tumor necrosis factor alpha mRNA and protein expression in the uteroplacental unit of mice with pregnancy loss. J Immunol 1998;160:4280-4288Google Scholar
  74. 74.
    Gorivodsky M, Torchinsky A, Zemliak I, Savion S, Fein A, Toder V: TGFβ2 mRNA expression and pregnancy failure in mice. Am J Reprod Immunol 1999;42:124-133Google Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Alexander Brill
    • 1
  • Arkady Torchinsky
    • 1
  • Howard Carp
    • 1
  • Vladimir Toder
    • 1
  1. 1.Department of Embryology and Teratology, Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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