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Regular Article |
a Department of Cell Biology, Medical School, Utrecht University, 3584 CX Utrecht, The Netherlands
b Department of Hematology, Erasmus University, 3015 GE Rotterdam, The Netherlands
c MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, 2333 AL Leiden, The Netherlands
d IRS, J.A. Cohen Institute, 2333 AL Leiden, The Netherlands
e Department of Internal Medicine, Erasmus University, 3015 GE Rotterdam, The Netherlands
f Department of Clinical Oncology, University Hospital Leiden, 2300 RC Leiden, The Netherlands
Today, many patients, who are often young, undergo total body irradiation (TBI) followed by bone marrow transplantation. This procedure can have serious consequences for fertility, but the long-term intratesticular effects of this treatment in primates have not yet been studied. Testes and epididymides of rhesus monkeys that received doses of 4–8.5 Gy of TBI at 2–4 yr of age were studied 3–8 yr after irradiation. In all irradiated monkeys, at least some seminiferous tubule cross-sections lacked germ cells, indicating extensive stem cell killing that was not completely repaired by enhanced stem cell renewal, even after many years. Testes totally devoid of germ cells were only found in monkeys receiving doses of 8 Gy or higher and in both monkeys that received two fractions of 6 Gy each. By correlating the percentage of repopulated tubules (repopulation index) with testicular weight, it could be deduced that considerable numbers of proliferating immature Sertoli cells were killed by the irradiation. Because of their finite period of proliferation, Sertoli cell numbers did not recover, and potential adult testis size decreased from approximately 23 to 13 g. Most testes showed some dilated seminiferous tubules, indicating obstructed flow of the tubular fluid at some time after irradiation. Also, in 8 of the 29 irradiated monkeys, aberrant, densely packed Sertoli cells were found. The irradiation did not induce stable chromosomal translocations in spermatogonial stem cells. No apparent changes were seen in the epididymides of the irradiated monkeys, and the size of the epididymis adjusted itself to the size of the testis. In the irradiated monkeys, testosterone and estradiol levels were normal, whereas FSH levels were higher and inhibin levels lower when testicular weight and spermatogenic repopulation were low. It is concluded that irradiation before adulthood has considerable long-term effects on the testis. Potential testis size is reduced, repopulation of the seminiferous epithelium is generally not complete, and aberrant Sertoli cells and dilated tubules are formed. The latter two phenomena may have further consequences at still longer intervals after irradiation.
1 Supported by a grant from The Netherlands Organization for Scientific Research (NWO).
2 Correspondence: Dirk G. de Rooij, Department of Cell Biology, University Medical Center Utrecht, AZU-RM G02.525, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. FAX: 31 302541797; d.g.derooij{at}med.uu.nl
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