PROLIFERATIVE RESPONSE OF MOUSE SPERMATOGONIAL STEM-CELLS AFTER IRRADIATION - A QUANTITATIVE MODEL ANALYSIS OF EXPERIMENTAL-DATA

The testes of CDF1 mice were irradiated with single doses of X-rays ra nging from 2-16 Gy. The number of haploid cells in the testis at diffe rent times after irradiation (42-350 days) was determined by one-param eter flow cytometry both for irradiated animals and for age-matched co ntrols. Based on literature data on the kinetics of the spermatogenesi s in mice, a mathematical model of the (hierarchical) germ tissue was developed. Using this model, the processes of radiation-induced cell l oss and subsequent recovery were simulated and free parameters of the model were estimated by fitting the model prediction to the experiment al data. One of the aims of the study was to investigate the kinetic b ehaviour of spermatogonial stem cells and the corresponding control me chanisms. In order to fit the data, the model has to include the follo wing features: (i) A preferential self-repopulation of spermatogonial stem cells following tissue injury. The model-estimated probability of a self-renewing division rises from 50% (the steady-state value) to 9 5% if the stem-cell population is reduced to 10% of its normal size. ( ii) A relatively low, almost constant turnover rate of the stem-cell c ompartment. It is suggested by the analysis that less than 10% of the permatogonial stem cells present in the testis divide per day, regardl ess of the degree of cellular depletion. (iii) A mechanism responsible for incomplete recovery. The observed incomplete recovery of spermato genesis after single doses exceeding 10 Gy can be described quantitati vely assuming that the stem cells are organized into discrete prolifer ative structures, the number of cells per structure being about 60.