Evaluation of testicular damage in adult rats exposed to doxorubicin at a critical stage of maturation.

Abstract

The present study aimed to evaluate the testicular damage induced in rats exposed to doxorubicin at a critical stage of maturation and the ability of rats to overcome this damage after sexual maturation. Male rats at 6 and 13 days old were treated with a cumulative dose of 6 mg/kg of doxorubicin and then sacrificed 7 days after treatment (20 days old) and after sexual maturation at age 80 days (9 weeks after doxorubicin treatment). Doxorubicin produced a significant reduction of testicular weight, depletion of the number of spermatogonia, reduction of seminiferous tubules diameters and seminiferous epithelium height, oxidative stress as well as significant increase in germ cells with abnormal DNA integrity profiles in young rats sacrificed after 7 days of doxorubicin treatment. Compared with the control, adult rats sacrificed after 9 weeks of doxorubicin treatment displayed testicular atrophy, massive germ cell loss accompanied by sharp decline in testicular morphometric parameters, spermiation failure and alteration of some androgen-dependent enzyme activities (acid phosphatase and lactate dehydrogenase were significantly decreased whereas that of gamma glutamyl transferase was significantly increased). Moreover, germ cell DNA breaks remained elevated and were associated with increased lipid peroxidation products and depressed glutathione level of testicular tissue. Thus, the present study showed that the administration of doxorubicin to early prepubertal rats caused an adverse impact effect on the adulthood stage fertility, reflecting a more long-lasting damage to the spermatogenic epithelium.