Long-term testicular toxicity caused by doxorubicin treatment during pre-pubertal phase

Doxorubicin is a potent drug widely used against different types of cancer and can cause damage to healthy tissues. Some studies have shown that this drug causes apoptosis of male germ cells. However, a detailed and long-term morphological study about the damages caused by doxorubicin administration to early prepubertal testis and to future fertility of the rat is missing. Male rats were treated at 15 days and 22 days with the dose of 5 mg/kg of doxorubicin and sacrificed at 40, 64 and 127 days of age. The testes were submitted to morphometric and stereological analyses. The reproductive capacity of the adult rats was also tested. The doxorubicin-treated rats showed germ cell depletion, tubular vacuolization, multinucleated formations of spermatids and germ cell showing apoptotic characteristics. Reduction of seminiferous tubule volume was observed in all doxorubicin-treated subgroups but the volume densities decreased only in the adult subgroup. The frequency of tubular sections containing type A spermatogonia was progressively reduced in these rats, which showed null fertility. Taken together the results of the present study we conclude that the administration of doxorubicin during early prepubertal age can lead to severe injury of the adult fertility.