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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 1;88(19):8710–8714. doi: 10.1073/pnas.88.19.8710

Protective effect of medroxyprogesterone acetate plus testosterone against radiation-induced damage to the reproductive function of male rats and their offspring.

B Jégou 1, J F Velez de la Calle 1, F Bauché 1
PMCID: PMC52579  PMID: 1833765

Abstract

This study attempted to protect spermatogenesis and the reproductive performance of rats against the effects of acute scrotal exposure to x-rays. Daily subcutaneous injections of medroxyprogesterone acetate (8 mg/kg) plus testosterone (1 mg/kg) (MT group) were administered for 55 days (experiment A) or 15 days (experiment B). The rats were irradiated (3 grays) on the last day of MT pretreatment (MTX group). In both experiments, on days 1 and 130 posttreatment, rats from each of the four groups (control, x-irradiated, MT, and MTX groups) were killed to measure the weight of the reproductive organs and the number of epididymal spermatozoa. Breeding was started 3 days posttreatment by housing all males from the four groups each with two virgin females for six successive periods of 19 days, separated by a period of 2 days. The percentage of fertile males, the litter size, postimplantation losses, and dominant lethal mutations were calculated. In experiment A, in the last fertility trial, animals of both sexes were selected at random from the progeny of each group (F1). When they were adults, their fertility was tested in a mating trial. A fertility trial was also performed with the F2 males. Our data essentially reveal that (i) in addition to their adverse quantitative effects on spermatogenesis, x-rays also produce a significant increase in dominant lethal mutations in all germ cell classes, including stem spermatogonia; (ii) the F1 and F2 male descendants of irradiated male rats provoked abnormal rates of postimplantation losses in their female mates; (iii) the short as well as the long MT pretreatment protects testicular function of irradiated rats; and (iv) in experiment A, MT pretreatment totally prevented qualitative damage to spermatozoa and protected the descendants of the irradiated animals against altered spermatogenesis as well as against genetic damage in germ cells. In conclusion, pretreatment with MT, even for a short period of time, offers a method for potentially reducing the toxic and genotoxic effects of irradiation on the male reproductive system.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CLERMONT Y., HARVEY S. C. DURATION OF THE CYCLE OF THE SEMINIFEROUS EPITHELIUM OF NORMAL, HYPOPHYSECTOMIZED AND HYPOPHYSECTOMIZED-HORMONE TREATED ALBINO RATS. Endocrinology. 1965 Jan;76:80–89. doi: 10.1210/endo-76-1-80. [DOI] [PubMed] [Google Scholar]
  2. Cacheiro N. L., Russell L. B., Swartout M. S. Translocations, the predominant cause of total sterility in sons of mice treated with mutagens. Genetics. 1974 Jan;76(1):73–91. doi: 10.1093/genetics/76.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev. 1972 Jan;52(1):198–236. doi: 10.1152/physrev.1972.52.1.198. [DOI] [PubMed] [Google Scholar]
  4. Dym M., Clermont Y. Role of spermatogonia in the repair of the seminiferous epithelium following x-irradiation of the rat testis. Am J Anat. 1970 Jul;128(3):265–282. doi: 10.1002/aja.1001280302. [DOI] [PubMed] [Google Scholar]
  5. Ehling U. H. Comparison of radiation-and chemically-induced dominant lethal mutations in male mice. Mutat Res. 1971 Jan;11(1):35–44. doi: 10.1016/0027-5107(71)90030-3. [DOI] [PubMed] [Google Scholar]
  6. Gardner M. J., Snee M. P., Hall A. J., Powell C. A., Downes S., Terrell J. D. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. BMJ. 1990 Feb 17;300(6722):423–429. doi: 10.1136/bmj.300.6722.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hopkinson C. R., Dulisch B., Gauss G., Hilscher W., Hirschhäuser C. The effect of local testicular irradiation on testicular histology and plasma hormone levels in the male rat. Acta Endocrinol (Copenh) 1978 Feb;87(2):413–423. doi: 10.1530/acta.0.0870413. [DOI] [PubMed] [Google Scholar]
  8. Kangasniemi M., Veromaa T., Kulmala J., Kaipia A., Parvinen M., Toppari J. DNA-flow cytometry of defined stages of rat seminiferous epithelium: effects of 3 Gy of high-energy X-irradiation. J Androl. 1990 May-Jun;11(3):312–317. [PubMed] [Google Scholar]
  9. Lu C. C., Meistrich M. L., Thames H. D., Jr Survival of mouse testicular stem cells after gamma of neutron irradiation. Radiat Res. 1980 Mar;81(3):402–415. [PubMed] [Google Scholar]
  10. Lyon M. F. X-ray-induced dominant lethal mutations in male guinea-pigs, hamsters and rabbits. Mutat Res. 1970 Aug;10(2):133–140. doi: 10.1016/0027-5107(70)90158-2. [DOI] [PubMed] [Google Scholar]
  11. Matsuda Y., Tobari I. Studies on radiation-induced chromosome aberrations in mouse spermatocytes. I. Stage specificity and dose-response relationships of chromosome aberrations induced in mouse primary spermatocytes following X-irradiation. Mutat Res. 1987 Feb;176(2):243–250. doi: 10.1016/0027-5107(87)90055-8. [DOI] [PubMed] [Google Scholar]
  12. Meistrich M. L., Finch M. V., Hunter N., Milas L. Protection of spermatogonial survival and testicular function by WR-2721 against high and low doses of radiation. Int J Radiat Oncol Biol Phys. 1984 Nov;10(11):2099–2107. doi: 10.1016/0360-3016(84)90208-6. [DOI] [PubMed] [Google Scholar]
  13. Meistrich M. L., van Beek M. E., Liang J. C., Johnson S. L., Lu J. Low levels of chromosomal mutations in germ cells derived from doxorubicin-treated stem spermatogonia in the mouse. Cancer Res. 1990 Jan 15;50(2):370–374. [PubMed] [Google Scholar]
  14. Milas L., Hunter N., Reid B. O. Protective effects of WR-2721 against radiation-induced injury of murine gut, testis, lung, and lung tumor nodules. Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):535–538. doi: 10.1016/0360-3016(82)90678-2. [DOI] [PubMed] [Google Scholar]
  15. Morris I. D., Delec J. I., Hendry J. H., Shalet S. M. Lack of protection by oestrogen from radiation-induced testicular damage in the rat. Radiother Oncol. 1988 Jan;11(1):83–89. doi: 10.1016/0167-8140(88)90048-5. [DOI] [PubMed] [Google Scholar]
  16. Nomura T. Parental exposure to x rays and chemicals induces heritable tumours and anomalies in mice. Nature. 1982 Apr 8;296(5857):575–577. doi: 10.1038/296575a0. [DOI] [PubMed] [Google Scholar]
  17. Oldfield E. H., Friedman R., Kinsella T., Moquin R., Olson J. J., Orr K., DeLuca A. M. Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection. J Neurosurg. 1990 May;72(5):737–744. doi: 10.3171/jns.1990.72.5.0737. [DOI] [PubMed] [Google Scholar]
  18. Schally A. V., Paz-Bouza J. I., Schlosser J. V., Karashima T., Debeljuk L., Gandle B., Sampson M. Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats. Proc Natl Acad Sci U S A. 1987 Feb;84(3):851–855. doi: 10.1073/pnas.84.3.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schlappack O. K., Delic J. I., Harwood J. R., Stanley J. A. Attempted protection of spermatogenesis from single doses of gamma-irradiation in the androgen pretreated rat. Arch Androl. 1987;19(3):269–274. doi: 10.3109/01485018708986827. [DOI] [PubMed] [Google Scholar]
  20. Searle A. G., Beechey C. V. Sperm-count, egg-fertilization and dominant lethality after X-irradiation of mice. Mutat Res. 1974 Jan;22(1):63–72. doi: 10.1016/0027-5107(74)90009-8. [DOI] [PubMed] [Google Scholar]
  21. Shu X. O., Gao Y. T., Brinton L. A., Linet M. S., Tu J. T., Zheng W., Fraumeni J. F., Jr A population-based case-control study of childhood leukemia in Shanghai. Cancer. 1988 Aug 1;62(3):635–644. doi: 10.1002/1097-0142(19880801)62:3<635::aid-cncr2820620332>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  22. Velez de la Calle J. F., Jégou B. Protection by steroid contraceptives against procarbazine-induced sterility and genotoxicity in male rats. Cancer Res. 1990 Feb 15;50(4):1308–1315. [PubMed] [Google Scholar]
  23. van Alphen M. M., van de Kant H. J., de Rooij D. G. Protection from radiation-induced damage of spermatogenesis in the rhesus monkey (Macaca mulatta) by follicle-stimulating hormone. Cancer Res. 1989 Feb 1;49(3):533–536. [PubMed] [Google Scholar]
  24. van Kroonenburgh M. J., van Daal W. A., Beck J. L., Vemer H. M., Rolland R., Herman C. J. Survival of spermatogonial stem cells in the rat after split dose irradiation during LH-RH analogue treatment. Radiother Oncol. 1987 May;9(1):67–73. doi: 10.1016/s0167-8140(87)80220-7. [DOI] [PubMed] [Google Scholar]

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