Abstract
The potential impact of an agent altering male reproductive function is greater for humans than for animals. Consequently, it is essential that sensitive criteria be used to look for effects on a multiplicity of target sites when an agent is evaluated using an animal model. No animal model has reproductive characteristics similar to those of humans, but this does not negate the validity of using animal models. Classic methodologies for reproductive toxicology are limited by the approaches used for subjective evaluation of testicular histology and use of natural mating for fertility tests. After dosing for an interval at least equal to six times the duration of one cycle of the seminiferous epithelium, sperm from ejaculated semen or the cauda epididymidis can be evaluated for normalcy of morphology or function and should be used for artificial insemination of females to critically evaluate fertility. Normal males of animal models ejaculate a great excess of sperm. A 50 or 90% reduction in the number of fertile sperm deposited during mating probably will not markedly reduce fertility. Artificial insemination of a critical number of sperm, selected to result in slightly less than maximal fertility for control animals, will maximize the probability of detecting a decrease in fertility if the same critical number of sperm is inseminated for treated animals as for control animals. Testicular function should be evaluated by objective, rather than subjective, criteria. For each male, a piece of testicular tissue should be appropriately fixed and an aliquot of parenchyma should be homogenized to allow enumeration of homogenization-resistant spermatids. Among the more sensitive criteria of testicular function are the minor diameter of essentially round seminiferous tubules, the ratio of leptotene spermatocytes to Sertoli cells, the corrected numbers of germ cells per seminiferous tubule cross section, and the number of homogenization-resistant spermatids per testis.
Full text
PDF









Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aafjes J. H., Vels J. M., Schenck E. Fertility of rats with artificial oligozoospermia. J Reprod Fertil. 1980 Mar;58(2):345–351. doi: 10.1530/jrf.0.0580345. [DOI] [PubMed] [Google Scholar]
- Amann R. P., Berndtson W. E. Assessment of procedures for screening agents for effects on male reproduction: effects of dibromochloropropane (DBCP) on the rat. Fundam Appl Toxicol. 1986 Aug;7(2):244–255. doi: 10.1016/0272-0590(86)90154-5. [DOI] [PubMed] [Google Scholar]
- Amann R. P., Lambiase J. T., Jr The male rabbit. I. Changes in semen characteristics and sperm output between puberty and one year of age. J Reprod Fertil. 1967 Oct;14(2):329–332. doi: 10.1530/jrf.0.0140329. [DOI] [PubMed] [Google Scholar]
- Amann R. P. Use of animal models for detecting specific alterations in reproduction. Fundam Appl Toxicol. 1982 Jan-Feb;2(1):13–26. doi: 10.1016/s0272-0590(82)80059-6. [DOI] [PubMed] [Google Scholar]
- Amann R. P., Wise M. E., Glass J. D., Nett T. M. Prepubertal changes in the hypothalamic-pituitary axis of Holstein bulls. Biol Reprod. 1986 Feb;34(1):71–80. doi: 10.1095/biolreprod34.1.71. [DOI] [PubMed] [Google Scholar]
- Berndtson W. E. Methods for quantifying mammalian spermatogenesis: a review. J Anim Sci. 1977 May;44(5):818–833. doi: 10.2527/jas1977.445818x. [DOI] [PubMed] [Google Scholar]
- Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev. 1972 Jan;52(1):198–236. doi: 10.1152/physrev.1972.52.1.198. [DOI] [PubMed] [Google Scholar]
- Desjardins C., Kirton K. T., Hafs H. D. Sperm output of rabbits at various ejaculation frequencies and their use in the design of experiments. J Reprod Fertil. 1968 Feb;15(1):27–32. doi: 10.1530/jrf.0.0150027. [DOI] [PubMed] [Google Scholar]
- Foote R. H., Berndtson W. E., Rounsaville T. R. Use of quantitative testicular histology to assess the effect of dibromochloropropane (DBCP) on reproduction in rabbits. Fundam Appl Toxicol. 1986 May;6(4):638–647. doi: 10.1016/0272-0590(86)90176-4. [DOI] [PubMed] [Google Scholar]
- Foote R. H., Schermerhorn E. C., Simkin M. E. Measurement of semen quality, fertility, and reproductive hormones to assess dibromochloropropane (DBCP) effects in live rabbits. Fundam Appl Toxicol. 1986 May;6(4):628–637. doi: 10.1016/0272-0590(86)90175-2. [DOI] [PubMed] [Google Scholar]
- Hagen D. R., Dziuk P. J. Detection of the effects of ingested caffeine on fertility of cocks by homospermic and heterospermic insemination. J Reprod Fertil. 1981 Sep;63(1):11–15. doi: 10.1530/jrf.0.0630011. [DOI] [PubMed] [Google Scholar]
- Hoffer A. P., Hinton B. T. Morphological evidence for a blood-epididymis barrier and the effects of gossypol on its integrity. Biol Reprod. 1984 May;30(4):991–1004. doi: 10.1095/biolreprod30.4.991. [DOI] [PubMed] [Google Scholar]
- Meistrich M. L. Critical components of testicular function and sensitivity to disruption. Biol Reprod. 1986 Feb;34(1):17–28. doi: 10.1095/biolreprod34.1.17. [DOI] [PubMed] [Google Scholar]
- Meistrich M. L., Finch M., da Cunha M. F., Hacker U., Au W. W. Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells. Cancer Res. 1982 Jan;42(1):122–131. [PubMed] [Google Scholar]
- Meistrich M. L., Samuels R. C. Reduction in sperm levels after testicular irradiation of the mouse: a comparison with man. Radiat Res. 1985 Apr;102(1):138–147. [PubMed] [Google Scholar]
- Mian T. A., Suzuki N., Glenn H. J., Haynie T. P., Meistrich M. L. Radiation damage to mouse testis cells from [99mTc] pertechnetate. J Nucl Med. 1977 Nov;18(11):1116–1122. [PubMed] [Google Scholar]
- Niwa K., Imai H., Kim C. I., Iritani A. Fertilization in vitro of hamster and mouse eggs in a chemically defined medium. J Reprod Fertil. 1980 Jan;58(1):109–114. doi: 10.1530/jrf.0.0580109. [DOI] [PubMed] [Google Scholar]
- Olar T. T., Amann R. P., Pickett B. W. Relationships among testicular size, daily production and output of spermatozoa, and extragonadal spermatozoal reserves of the dog. Biol Reprod. 1983 Dec;29(5):1114–1120. doi: 10.1095/biolreprod29.5.1114. [DOI] [PubMed] [Google Scholar]
- Robb G. W., Amann R. P., Killian G. J. Daily sperm production and epididymal sperm reserves of pubertal and adult rats. J Reprod Fertil. 1978 Sep;54(1):103–107. doi: 10.1530/jrf.0.0540103. [DOI] [PubMed] [Google Scholar]
- Russell L. D., Lee I. P., Ettlin R., Malone J. P. Morphological pattern of response after administration of procarbazine: alteration of specific cell associations during the cycle of the seminiferous epithelium of the rat. Tissue Cell. 1983;15(3):391–404. doi: 10.1016/0040-8166(83)90071-x. [DOI] [PubMed] [Google Scholar]
- STEINBERGER E. A quantitative study of the effect of an alkylating agent (triethylenemelamine) on the seminiferous epithelium of rats. J Reprod Fertil. 1962 Apr;3:250–259. doi: 10.1530/jrf.0.0030250. [DOI] [PubMed] [Google Scholar]
- SWIERSTRA E. E., WHITEFIELD J. W., FOOTE R. H. ACTION OF AMPHOTERICIN B (FUNGIZONE) ON SPERMATOGENESIS IN THE RABBIT. J Reprod Fertil. 1964 Feb;7:13–19. doi: 10.1530/jrf.0.0070013. [DOI] [PubMed] [Google Scholar]
- Turner T. T., Reich G. W. Cauda epididymal sperm motility: a comparison among five species. Biol Reprod. 1985 Feb;32(1):120–128. doi: 10.1095/biolreprod32.1.120. [DOI] [PubMed] [Google Scholar]
