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

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 hnjections 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 irgin females for six successive periods of 19 days, separated by a period of 2 days.The percentage offertile 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 (FI).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. Radiation has particularly severe adverse effects on spermatogenesis and therefore on fertility in both animals and man (1). Radiation therapy is nevertheless widely used because there is often no other choice for the treatment of a number of cancers in children and adults. The prevention of gonadal damage during radiotherapy is therefore a major concern. Since shielding the testes offers only poor protection to spermatogenesis, various other experimental approaches, aimed at preventing radiation-induced quantitative damage to the gonads, have been explored (2-8). Some of these have achieved protection of testicular function to various degrees (2-5, 8). However, a major limitation of these studies is that the reproductive performances of the experimental animals and of their progeny was not assessed. It is known that in addition to azoo-or oligozoospermia, radiation also produces germ-line mutations leading to inherited anomalies in rodents (9-13) an...

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