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Mutation Research, 290 (1993) 193-200 193 © 1993 Elsevier Science Publishers B.V. All rights reserved 0027-5107/93 /$06.00 MUT 05318 A quantitative study of spermatogonial multiplication and stem cell renewal in the C3H/101 F 1 hybrid mouse Ruud A.J. Tegelenbosch * and Dirk G. de Rooij Department of Cell Biology, Medical School, Utrecht University, Postbus 80.175, 3508 TD Utrecht, The Netherlands (Received 31 March 1993) (Revision received 1 July 1993) (Accepted 8 July 1993) Keywords: C3H/101 F 1 hybrid mice; Spermatogenesis; Kinetics; Spermatogonial stem cells Summary In whole mounts of seminiferous tubules of C3H/101 F 1 hybrid mice, spermatogonia were counted in various stages of the epithelial cycle. Furthermore, the total number of Sertoli cells per testis was estimated using the disector method. Subsequently, estimates were made of the total numbers of the different spermatogonial cell populations per testis. The results of the cell counts indicate that the undifferentiated spermatogonia are actively proliferat- ing from stage XI until stage IV. Three divisions of the undifferentiated spermatogonia are needed to obtain the number of A 1 plus undifferentiated spermatogonia produced each epithelial cycle. Around stage VIII almost two-thirds of the Apr and all of the Aal spermatogonia differentiate into A~ spermatogonia. It was estimated that there are 2.5 × 106 differentiating spermatogonia and 3.3 × 105 undifferentiated spermatogonia per testis. There are about 35,000 stem cells per testis, constituting about 0.03% of all germ cells in the testis. It is concluded that the undifferentiated spermatogonia, including the stem cells, actively proliferate during about 50% of the epithelial cycle. Genetic risk assessment for men is mainly based on results from animal tests and in particu- lar the mouse (UNSCEAR, 1988). Studies on radiation induced genetic damage in mammalian stem cell spermatogonia revealed a humped dose-effect relationship (Lyon and Morris, 1969; Searle et al., 1969; Savkovic and Lyon, 1970; IAonard and DeKnudt, 1971). This is assumed to be the result of the relation between the induc- * Corresponding author. Tel. (31) 30 534332; Fax (31) 30 537419. tion of cell death and genetic changes (Russell, 1956; Oftedal, 1986; Gerber and L6onard, 1971). Based on data available on the induction of recip- rocal translocation in C3H/101 F 1 hybrid (3H1) mice Leenhouts and Chadwick (1981) developed a model explaining this relation. With respect to the sensitivity of the induction of spermatogonial stem cell death in this mouse only indirect data on the duration of the sterile period or the testis weight after irradiation are available (Cattanach, 1974). Furthermore, for the 3H1 mouse no quan- titative data are available on spermatogonial numbers and the period during the epithelial