Reversibility of the effects of the chemotherapeutic regimen for non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone, on the male rat reproductive system and progeny outcome.
The chemotherapeutic agents used to treat non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), have adverse effects on male reproductive function and progeny outcome. To determine the reversibility of these effects, male rats received a CHOP treatment mimicking human exposure. CHOP reduced testicular and epididymal weights; these remained decreased after 9 weeks recovery. This treatment also decreased testicular sperm number and increased spermatozoal DNA damage. Although sperm production returned to control values after 9 weeks recovery, DNA damage persisted. Decreased litter size, and increased pre- and post-implantation losses were observed among litters sired by CHOP-exposed males. Litter size and pre-implantation loss returned to control within 3 weeks post-treatment and post-implantation loss by 6 weeks. Thus, effects of CHOP on progeny outcome were reversed 9 weeks post-treatment, although germ cell DNA breaks remained elevated. These data suggest that the ability to sire viable progeny may not be a sensitive measure of spermatozoal quality in rats.
Delbès
Geraldine
G
Department of Pharmacology & Therapeutics, McGill University, Montréal, Québec, Canada.
Vaisheva
Farida
F
Luu
Trang
T
Marcon
Ludovic
L
Hales
Barbara F
BF
Robaire
Bernard
B
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002985:Clinical Protocols; D003520:Cyclophosphamide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004822:Epididymis / Q000187:drug effects; D005260:Female; D006801:Humans; D008098:Litter Size / Q000187:drug effects; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D011241:Prednisone / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D013076:Sperm Count; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D016896:Treatment Outcome; D014750:Vincristine / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone