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Journal of Andrology, Vol 3, Issue 1 58-68, Copyright © 1982 by The American Society of Andrology

Quantitative Correlation Between Testicular Stem Cell Survival, Sperm Production, and Fertility in the Mouse After Treatment With Different Cytotoxic Agents

MARVIN L. MEISTRICH 1

1 Department of Experimental Radiotherapy, The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, Texas

Treatment of mice with high doses of radiation or certain cytotoxic drugs results in killing of spermatogonial stem cells, a prolonged period of reduced sperm production, and infertility. In this study, quantitative relationships between these parameters are shown to exist after radiation, Adriamycin® (Adria Laboratories, Wilmington, Delaware) or thiotepa treatment. The same relationships are valid for the different cytotoxic agents tested.

The survival of spermatogonial stem cells was assessed by counts of repopulating tubule cross sections at five or eight weeks after treatment. Testicular sperm head counts, eight weeks after treatment, were also used as an assay of stem cell survival. These two assays are highly correlated, demonstrating that the sperm head count at eight weeks is directly related to stem cell survival.

Sperm production declines after cytotoxic treatment and partially recovers to a plateau level. The level of this recovery is correlated with stem cell survival. The restoration of fertility is related to the recovery of sperm production. Under the conditions employed, fertility returns when sperm production by the testis reaches about 10% of control levels. The duration of the sterile period is also highly correlated with stem cell survival.

These results strongly suggest that shortterm assays that measure survival of stem cells can be used to predict the duration and extent of sterility, regardless of the cytotoxic agent used.

     Key words: stem cells, sperm production, fertility, radiation, Adriamycin

Submitted on February 20, 1981
Revised on April 14, 1981
Accepted on June 17, 1981




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Copyright © 1982 by The American Society of Andrology.