Differential susceptibility of immature rat testes to doxorubicin at critical stages of maturation. Biochemical and functional assessment.
The toxic effects of doxorubicin on the reproductive system of the male rat were studied at different susceptible stages of postnatal development. A multidisciplinary approach including the assessment of histopathological, functional and biochemical parameters was chosen. Groups of male rats were treated once with the compound (3 mg/kg) on postnatal day 6, 16, 24 or 45. Both the onset of reproductive capacity and fertility were determined by serially mating ten animals per group for 12 weeks beginning at the age of 45 days. Reproductive organ weights, sperm counts and epididymal androgen binding protein (ABP) were measured at intermediate (80-day-old rats) or terminal sacrifice (129-day-old rats). Age dependent differential doxorubicin toxicity was evident. Treatment of 6-day-old animals with doxorubicin severely impaired development of reproductive functions. Treatment of 16-day-old animals reduced fertility throughout the mating study, as well as body and reproductive organ weights and sperm counts. Initial toxicity was observed in the group treated at 24 days of age; particularly, low reproductive organ weights and low sperm counts were found. These findings proved reversible towards the end of the study. Neither biochemical nor functional impairment of the reproductive system could be observed in the group treated at 45 days of age.
Bechter
R
R
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Haebler
R
R
Ettlin
R A
RA
Haseman
J K
JK
Dixon
R L
RL
D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects; D005298:Fertility / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013076:Sperm Count; D013737:Testis / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D013997:Time Factors
D004317:Doxorubicin