Reduction in Sperm Levels after Testicular Irradiation of the Mouse: A Comparison with Man

The potential and limitations of applying extrapolation factors (EFs) to the results of animal studies to predict effects of toxic agents on human male fertility were evaluated using radiation data. The EF is the ratio of the dose to produce a given effect in the mouse to that necessary to produce the same effect in man. Sperm counts in mouse testes were compared to those in the ejaculates of human males (D. K. Clifton and W. J. Bremner, J. Androl. 4, 387-392 (1981)) at several different times after irradiation. EFs of between 2.6 and 7 were obtained at the time when minimum counts occur. However, it must be noted that the sperm being measured arose from different cell types: differentiating spermatogonia in the mouse vs stem spermatogonia in man. Sperm counts performed at times at which the sperm develop from irradiated stem cells in both species yielded EFs between 11 and 44. However, if sufficient time was allowed for maximum recovery in both species, the EF was less than 1.7. These results indicate that man appears to be much more sensitive than the mouse to the testicular effects of irradiation at 2 to 9 months postexposure, but both species are comparable in their sensitivity to irreversible damage. The use of EFs may be appropriate, but since the EF is very dependent on the time at which the comparison was made, different values must be used for prompt and permanent testicular injury.