Summary
The primordial germ cells originate in the region of the caudal end of the primitive streak, root of the allantois, and yolk sac splanchnopleure, and migrate to the gonadal ridges where they divide to form the oogonia of the female and gonocytes of the male. In the female, the transition to oocytes occurs in utero, and the female mammal is born with a finite number of oocytes that cannot be replaced. By contrast, the gonocytes of the male initiate divisions soon after birth to form the spermatogonial stem cells, which persist throughout reproductive life of the male and are capable of regenerating the seminiferous epithelium after injury. As a result of these basic differences in gametogenesis, the response of the male and female to radiation and chemicals is different. Any loss of oocytes in the female cannot be replaced, and if severe enough, will result in a shortening of the reproductive span. In the male, a temporary sterile period may be induced owing to destruction of the differentiating spermatogonia, but the stem cells are the most resistant spermatogonial type, are capable of repopulating the seminiferous epithelium, and fertility usually returns. The response of both the male and female changes with development of the embryonic to the adult gonad, and with differentiation and maturation in the adult. The primordial germ cells, early oocytes, and differentiating spermatogonia of the adult male are unusually sensitive to the cytotoxic action of noxious agents, but each agent elicits a specific response owing to the intricate biochemical and physiological changes associated with development and maturation of the gametes. The relationship of germ cell killing to fertility is direct, and long-term fertility effects can be predicted from histological analysis of the gonads. The relationship to genetic effects, on the other hand, is indirect, and acts primarily by limiting the cell stages available for testing, by affecting the distribution of mitotically active stem cells among the different stages of the mitotic cycle, and thereby changing both the type and frequency of genetic effects observed.
By acceptance of this article, the publisher or recipient acknowledges the U.S. Government’s right to retain a nonexclusive, royalty-free license in and to any copyright covering the article.
Research sponsored by the Office of Health and Environmental Research, U. S. Department of Energy under contract W-7405-eng-26 with the Union Carbide Corporation.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Baker, T. G. (1973) The effects of ionizing radiation on the mammalian ovary with particular reference to oogenesis, InHandbook of Physiology, Section 7:Endocrinology, Volume II,Female Reproductive System, Part 1, R. O. Greep, B. A. Astwood, S. R. Geiger, Eds. , American Physiologcal Society, Washington, D. C. , pp. 349 – 361.
Beaumont, H. M. (1960) Changes in the radiosensitivity of the testis during foetal development.Int. J. Rad. Biol. 2: 247 – 256.
Beaumont, H. M. (1961) Radiosensitivity of oogonia and oocytes in the foetal rat.Int. J. Rad. Biol. 3: 59 – 72.
Benda, C. (1887) Untersuchungen uber den Bau des funktionerierenden Samenkanalchens einiger Saugetiere und Folgerungen fur die Spermatogenese dieser Wirbeltierklasse. Arch. Anat. Microsc. Morphol. Exp. 30: 49 – 110.
Bhattacharjee, D. , T. K. Shetty, and K. Sundaram (1978) Cytotoxicity of ethyl methanesulfonate in mice spermatogonia.Experientia35 (5): 630 – 631.
Brambell, F. W. R. (1927) The development and morphology of the gonads of the mouse. I. The morphogenesis of the indifferent gonad and of the ovary.Proc. Roy. Soc. Lond. B 101: 391 – 408.
Brenneke, H. (1937) Strahlenschadigung von Mause - und Rattensperma, beobachtet an der Fruhent wicklung der Eier.Strahlentherapie60: 214 – 238.
Brewen, J. G. , H. S. Payne, K. P. Jones, and R. J. Preston (1975) Studies on chemically induced dominant lethality. I. The cytogenetic basis of MMS and induced dominant lethality in post–-meiotic male germ cells.Mut. Res. 33: 239 – 250.
Bullough, W. S. (1948) Mitotic activity in the adult male mouse, Mus musculus L. The diurnal cycles and their relation to waking and sleeping.Proc. Roy. Soc. B 135: 212 – 233.
Cattanach, B. M. , C. E. Pollard, J. H. Isaacon (1968) Ethyl methanesulfonate-induced chromosome breakage in the mouse.Mut. Res. 6: 297 – 307.
Chang, M. C. , D. M. Hung, and E. B. Romanoff (1957) Effects of radio-cobalt irradiation of rabbit spermatozoa in vitro on fertilization and early development.Anat. Rec. 129: 211 – 229.
Chiquoine, A. D. (1954) The identification, origin, and migration of the primordial germ cells in the mouse embryo.Anat. Rec. 118: 135 – 146.
Clermont, Y. (1968) Differenciation et evolution des cellules sexuelles 1. La lignee male. Cinetique de la spermatogenese chez les Mammiferes, InLa Physiologie de la Reproduction les Mammiferes, A. Jost, Ed. , Editions du centre National de la Recherche Scientifique, Paris, pp. 7 – 60.
Clermont, Y. , and E. Bustos-Obregon (1968) Re-examination of spermatogonial renewal in the rat by means of seminiferous tubules mounted “in toto”.Am. J. Anat. 122: 237 – 248.
Clermont, Y. , and S. C. Harvey (1965) Duration of the cycle of the seminiferous epithelium of normal, hypophysectomized and hypophysectomized - hormone treated albino rats.Endocrinol. 76: 80 – 89.
Cox, B. D. , and M. F. Lyon (1975) X-ray induced dominant lethal nutations in mature and immature oocytes of guinea-pigs and golden hamsters.Mut. Res. 28: 421 – 436.
Dobson, R. L. , and J. S. Felton (1983) Female germ-cell loss from radiation and chemical exposures.Symposium on“Reproductivef Toxicology”, D. R. Mattison, Ed. , Am. J. Indust. ted. 4:nos. 1 and 2.
Ebner, V. von (1871)Untersuchungen uber den Bau der Samenkanalchen und die Entwicklung der Spermatozoiden bei den Saugethieren und beim Menschen. Leipzig.
Eddy, E. M. , S. M. Clark, D. Gong, and B. A. Fenderson (1981) Review article: Origin and migration of primordial germ cells in mammals.Gamete Res. 4: 333 – 362.
Edwards, R. G. , and J. L. Sirlin (1958) The effect of 200r of X-rays on the rate of spermatogenesis and spermiogenesis in the mouse.Exp. Cell Res. 15: 522 – 528.
Ehling, U. H. (1978) Specific–locus mutations in mice, InChemical Mutagens, Vol. 5, A. Hollaender, and F. J. de Serres, Eds. , Plenum Publishing Co. , New York, pp. 233 - 256.
Ehling, U. H. , D. G. Doherty, and H. V. Mailing (1972) Differential spermatogenic response of mice to the induction of dominant lethal mutations by n-propyl methanesulfonate and isopropyl methanesulfonate.Mut. Res. 15: 175 – 184.
Ehling, U. H. , and A. Neuhauser (1979) Procarbazine-induced specific-locus mutations in male mice.Mut. Res. 59: 245 – 256.
Falconer, D. S. , B. M. Slizynski, and C. Auerbach (1951) Genetical effects of nitrogen mustard in the house mouse.Jour, of Genetics10: 81 – 88.
Generoso, M. (1969) Chemical induction of dominant lethals in female mice. Genetics 61: 461 – 470.
Generoso, W. M. , personal communication.
Generoso, W. M. , J. B. Bishop, D. G. Gosslee, G. W. Newell, C. J. Sheu, and E. von Halle (1980) Heritable translocation test in mice.Mut. Res. 76: 191 – 215.
Generoso, W. M. , K. T. Cain, and S. W. Huff (1978) Chromosomal aberration effects of benzo[a]pyrene in male and female germ cells of mice.Mut. Res. 53: 126.
Generoso, W. M. , S. K. Stout, and S. W. Huff (1971) Effects of alkylating chemicals on reproductive capacity of adult female mice.Mut. Res. 13: 171 – 184.
Generoso, W. M. , K. T. Cain, and S. W. Huff (1978) Inducibility by chemical mutagens of heritable translocations, InAdvances in Modern Toxicology, W. G. Flamm and M. A. Mehlman, Eds. , Hemisphere, Washington, D. C. , pp. 109 – 129.
Generoso, W. M. , S. W. Huff, and K. T. Cain (1979) Relative rates at which dominant–lethal mutations and heritable translocations are induced by alkylating chemicals in postmeiotic male germ cells of mice.Genetics93: 163 – 171.
Generoso, W. M. , S. W. Huff, and S. K. Stout (1971) Chemically induced dominant-lethal mutations and cell killing in mouse oocytes in the advanced stages of follicular development.Mut. Res. 11: 411 – 420.
Generoso, W. M. , M. Krishna, R. E. Sotomayor, and N. L. A. Cacheiro (1977) Delayed formation of chromosome aberrations in mouse pachytene spermatocytes treated with triethylenemelamine (TEM).Genetics85: 65 – 72.
Generoso, W. M. , R. J. Preston, and J. G. Brewen (1975) 6-mercaptopurine, an inducer of cytogenetic and dominant-lethal effects in premeiotic and early meiotic germ cells of male mice.Mut. Res. 28:437–447.
Generoso, W. M. , and W. L. Russell (1969) Strain and sex variations in the sensitivity of mice to dominant-lethal induction with ethyl methanesulfonate.Mut. Res. 8: 589 – 598.
Generoso, W. M. , W. L. Russell, S. W. Huff, S. K. Stout, and D. G. Gosslee (1974) Effects of dose on the induction of dominant-lethal mutations and heritable translocations with ethyl methanesulfonate in male mice.Genetics77: 741 – 752.
Grell, R. F. , and E. E. Generoso (1982) A temporal study at the ultrastructural level of the developing pro–oocyte of Drosophila melanogaster.Chromosoma87: 49 – 75.
Grell, R. F. , E. F. Oakberg, and E. E. Generoso (1980) Synaptonemal complexes at premeiotic interphase in the mouse.Proc. Natl. Acad. Sci. USA77: 6720 – 6723.
Gulyas, B. J. , and D. R. Mattison (1979) Degeneration of mouse oocytes in response to polycyclic aromatic hydrocarbons.Anat. Rec. 193: 863 – 880.
Hannah–Alava, A. (1965) The premeiotic stages of spermatogenesis, InAdvances in Genetics, E. W. Caspari, Ed. , Vol. 13, Academic Press, New York, pp. 157 – 224.
Huckins, C. (1965)The initiation of spermatogenesis in the testis of the Wistar albino rat. Ph. D. dissertation, MsGill University, Montreal, Canada.
Huckins, C. (1971a) The spermatogonial stan cell population in adult rats. I. Their morphology, proliferation and maturation.Anat. Rec. 169: 533 – 558.
Huckins, C. (1971b) The spermatogonial stem cell population in adult rats. III. Evidence for a long–cycling population.Cell Tissue Kinet. 4: 335 – 349.
Huckins, C. (1972) Spermatogonial stem cell behavior in rodents, InBiology of Reproduction, Basic and Clinical Studies, Vol. Ill, J. T. Velardo and B. A. Kasprcw, Eds. , Pan American Congress of Anatomy, New Orleans, Louisiana, pp. 395 – 421.
Huckins, C. (1978) Spermatogonial intercellular bridges in whole–mounted seminiferous tubules from normal and irradiated rodent testes.Am. J. Anat. 153: 97 – 122.
Huckins, C. , and E. F. Oakberg (1978) Morphological and quantitative analysis of spermatogonia in mouse testes using whole mounted seminiferous tubules II. The irradiated testis.Anat. tec. 192: 529 – 542.
Jackson, H. (1958) The effects of radiomimetric chemicals on the fertility of male rats.The Journal of the Faculty of RadiologistsIX (4): 216 – 220.
Jackson, H. , B. W. Fox, and A. W. Craig (1961) Antifertility substances and their assessment in the male rodent.J. Reprod. Fertil. 2: 447 – 465.
Jacox, H. W. (1939) Recovery following human ovarian irradiation.Radiology32: 538 – 545.
Krarup, T. (1969) Oocyte destruction and ovarian tumorigenesis after direct application of a chanical carcinogen (9:10–dimethyl–1:2–Benzanthrene) to the mouse ovary.Int. J. Cancer4: 61 – 75.
LaValette, St. George von (1876) Uber die Genese der Samenkorper 1.Arch. Anat. Microsc. Morphol. Exp. 1: 403 – 414.
Leblond, C. P. , and Y. Clermont (1952) Definition of the stages of the cycle of the seminiferous epithelium in the rat.Ann. N. Y. Acad. Sci. 55: 548 – 573.
Leonard, A. (1976) Heritable chromosome aberrations in mammals after exposure to chemicals.Rad. and Environm. Biophys. 13: 1 – 8.
Lu, C. C. , and M. Meistrich (1979) Cytotoxic effects of chemotherapeutic drugs on mouse testis cells.Cancer Res. 39: 3575 – 3582.
Mandl, A. M. (1964) The radiosensitivity of germ cells.Biol. Rev. 39: 288 – 371.
Mattison, D. R. , L. Chang, S. S. Thorgeirsson and K. Shiromizu (1981) The effects of cyclophosphamide, azathioprene, and 6-mercaptopurine on oocyte and follicle number in C57BL/6N mice.Res. Commun. Chem. Path. Pharmacol. 31: 155 – 161.
Mattison, D. R. , and M. S. Nightingale (1980) The biochemical and genetic characteristics of marine ovarian aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity and its relationship to primordial oocyte destruction by polycyclic aromatic hydrocarbons.Tox. & Appl. Pharm. 56: 399 – 408.
Mattison, D. R. , and M. S. Nightingale (1981) Murine ovarian benzo[a]pyrene metabolism and primordial oocyte destruction: A survey of nine inbred strains, InDynamics of Ovarian Function, N. B. Schwartz, and M. Hunzicker–Dunn, Eds. , Raven Press, New York, pp. 89 – 94.
Mattison, D. R. , and M. S. Nightingale (1982) Prepubertal ovarian toxicity.Banbury Report11: 395 – 409.
Mintz, B. (1960) Embryological phases of nammalian gametogenesis.J. Cell Comp. Physiol. 56; Supp. 1: 31 – 48.
Monesi, V. (1962) Autoradiographic study of DNA synthesis and the cell cycle in spermatogonia and spermatocytes of mouse testis using tritiated thymidine. J. Cell, Biol. 14: 1 – 18.
Monesi, V. (1962) Relation between X ray sensitivity and stages of the cell cycle in spermatogonia of the mouse.Rad. Res. 17: 809 – 838.
Murray, J. M. (1931) A study of the histological structure of the mouse ovaries following exposure to roentgen irradiation.Am. J. Roentgenol. Radium Ther. Nucl. Med. 25: 1 – 45.
Necas, E. (1982) Stem cell (CFU-s) proliferation in sublethally irradiated mice.Cell Tissue Kinet. 15: 667 – 672.
Oakberg, E. F. (1955) Degeneration of spermatogonia of the mouse following exposure to X–rays, and stages in the mitotic cycle at which cell death occurs.J. Morph. 97:39– 54.
Oakberg, E. F. (1956a) A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal.Am. J. Anat. 99: 391 – 413.
Oakberg, E. F. (1956b) Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium.Am. J. Anat. 99: 507 – 516.
Oakberg, E. F. (1962) Gamma-ray sensitivity of oocytes of immature mice.Proc. Soc. Expl. Biol. Med. 109: 763 – 767.
Oakberg, E. F. (1966) Effect of 25R of X-rays at 10 days of age on oocyte numbers and fertility of female mice, InRadiation and Aging, P. J. Lindop, and G. A. Sacher, Eds. , Taylor & Frances LTD, London, England, pp. 293 – 306.
Oakberg, E. F. (1968) Relationship between stages of follicular development and RNA synthesis in the mouse oocyte.Mut. Res. 6: 155 – 165.
Oakberg, E. F. (1971) Spermatogonial stem-cell renewal in the mouse.Anat. Rec. 169: 515 – 532.
Oakberg, E. F. (1975) Effects of radiation on the testis, InHandbook of Physiology, Section 7:Endocrinology, Volume V, Male Reproductive System, R. O. Greep, E. B. Astwood, D. W. Hamilton, and S. R. Geiger, Eds. , American Physiological Society, Vfeshington, D. C. , pp. 233 – 243.
Oakberg, E. F. (1978) Differential spermatogonial stem-cell survival and mutation frequency.Mut. Res. 50: 327 – 340.
Oakberg, E. F. (1979) Timing of oocyte maturation in the mouse and its relevance to radiation–induced cell killing and mutational sensitivity.Mut. Res. 59: 39 – 48.
Oakberg, E. F. (1981) The age at which the long-cycling spermatogonial stem-cell population is established in the mouse, InDevelopment and Function of the Reproductive Organs, A. G. Byskov, and H. Peters, Eds. , Excerpta Medica, Amsterdam, pp. 149 – 152.
Oakberg, E. F. , Crosthwait, C. D. , and Raymer, G. D. (1982) Spermatogenic stage sensitivity to 6-mercaptopurine in the mouse.Mut. Res. 94: 165 – 178.
Oakberg, E. F. , and C. D. Crosthwait (1983) The effect of ethyl-methyl- and hydroxyethyl-nitrosourea on the mouse testis.Mut. Res. 108: 337 – 344.
Oakberg, E. F. , and R. L. DiMinno (1960) X-ray sensitivity of primary spermatocytes of the mouse.Intern. J. Radiation Biol. 2: 196 – 209.
Oakberg, E. F. , and C. Huckins (1976)-Spermatogonial stem cell renewal in the mouse as revealed by H-thymidine labeling and irradiation, InStem Cells of Renaming Cell Populations, A. B. Cairnie, P. K. Lala, and D. G. Osmond, Eds. , Academic Press, New York, pp. 287 – 302.
Parsons, D. F. (1962) An electron microscope study of radiation damage in the mouse oocytes.J. Cell. Biol. 14: 31 – 48.
Partington, M. , B. W. Fox, and H. Jackson (1964) Comparative action of some urethane sulphonic esters on the cell population of the rat testis. Exptl.Cell Res. 33: 78 – 88.
Pfcdersen, T. , and H. Peters (1968) Proposal for a classification of oocytes and follicles in the mouse ovary.J. Reprod. Fertil. 17: 555 – 557.
Peters, H. (1969) The effect of radiation in early life on the morphology and reproductive function of the mouse ovary, InAdvances in Reproductive Physiology, A. Mclaren, Ed. , Academic Press, New York, pp. 149 – 185.
Regaud, C. (1901) Etudes sur la structure des tubes seminferes et sur la spermatogenese chez les Martmiferes.Arch. Anat. Micr. 4: 101 – 156.
Regaud, C. , et A. Lacassagne (1927) Effects histophysiologique des Rayons de Roentgen et de Becquerel– Curie sur les tissues adultes normaux des animaux superieurs.Arch, de’l Institute due Radium, Vol. 1.
Rooij, D. G. de (1973) Spermatogonial stem cell renewal in the mouse 1. Normal situation.Cell Tissue Kinet. 6: 281 – 287.
Roosen–Runge, E. C. (1962) The process of spermatogenesis in mammals.Biol. Rev.37: 343 – 377.
Rowley, M. J. , D. R. Leach, G. A. Warner, and C. G. Heller (1974) Effect of graded doses of ionizing radiation on the human testis.Rad. Res. 59: 665 – 678.
Rubin, N. H. (1982) Influence of the circadian rhythm in cell division on radiation-induced mitotic delay in vivo.Rad. Res. 89: 65 – 76.
Ruiter–Bootsma, A. L. de, M. F. Kramer, D. G. de Rooij, and J. A. G. Davids (1976) Response of stem cells in the mouse testis to fission neutrons of 1 MeV energy and 300 k V X– rays, methodology, dose-response studies, relative biological effectiveness.Rad. Res. 67: 56 – 68.
Russell, W. L. (1965) Effect of the interval between irradiation and conception on mutation frequency in female mice.Proc. Natl. Acad. Sci. USA54: 1552 – 1557.
Russell, W. L. , E. M. Kelly, P. R. Hunsicker, J. W. Bangham, S. C. Maddux, and E. L. Phipps (1979) Specific–locus test shows ethylnitrosourea to be the most potent mutagen in the mouse.Proc. Natl. Acad. Sci. USA76(11) -. 5818 – 5819.
Sapsford, C. S. (1962) Changes in the cells of the sex cords and seminiferous tubules during the development of the testis of the rat and mouse.Aust. jJ. Zool. 10: 178 – 195.
Selby, P. B. (1973) X-ray-induced specific–locus mutation rate in newborn male mice.Mat. Res. 18: 63 – 75.
Sharma, R. K. , G. T. Roberts, F. M. Johnson, and H. V. Mailing (1979) Translocation and sperm abnormality assays in mouse spermatogonia treated with procarbazine.Mut. Res. 67: 385 – 388.
Sotomayor, R. E. , and R. B. Qjmming (1975) Induction of translocations by cyclophosphamide in different germ cell stages of male mice: Cytological characterization and transmission.Mut. Res. 27: 375 – 388.
Steinberger, E. (1962) A quantitative study of the effect of an alkylating agent (triethylenemelamine) on the seminiferous epithelium of rats.J. Reprod. Eertil. 3: 250 – 259.
Walker, H. C. (1977) Comparative sensitivities of meiotic prcphase stages in male mice to chromosome damage by acute X– and chronic gamma-irradiation.Mut. Res. 44: 427 – 432.
Witschi, E. (1948) Migration of the germ cells of human embryos from the yolk sac to the primitive gonadal folds.Contrib. Embryol.Cctrnegie Inst. 32: 67 – 80.
Zimmer, K. (1953) Rontgenbestrahlung der Ovarien und nachfolgenden Konzeption.Strahlen Therapie92: 117 – 122.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1984 Plenum Press, New York
About this chapter
Cite this chapter
Oakberg, E.F. (1984). Germ Cell Toxicity: Significance in Genetic and Fertility Effects of Radiation and Chemicals. In: Chu, E.H.Y., Generoso, W.M. (eds) Mutation, Cancer, and Malformation. Environmental Science Research, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2399-0_26
Download citation
DOI: https://doi.org/10.1007/978-1-4613-2399-0_26
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-9463-4
Online ISBN: 978-1-4613-2399-0
eBook Packages: Springer Book Archive