Search

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., (Copyright 2010 Elsevier Inc. All rights reserved.)

Chemotherapy of non-Hodgkin lymphoma (NHL) with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is associated with significant gonadal damage. Our goal was to determine the impact of CHOP chemotherapy on the male reproductive system, fertility, and progeny outcome in the rat model. Adult male Sprague-Dawley rats received saline or CHOP, 4 cycles of 3 weeks each, at doses analogous to 1/3x, 2/3x, or 1x the human dose; males were mated to evaluate effects on progeny outcome. Reproductive organ weights were significantly decreased in the 1x CHOP-exposed group. The spermatozoal contents of the testes and epididymides were decreased in 1x CHOP-treated males; the 1/3x and 2/3x doses also affected testicular sperm contents. Seminiferous tubule diameters were decreased by 20% in 1x CHOP-treated males. Damage ranged from the presence of small vacuoles in the epithelium to tubules deprived of spermatocytes and spermatids and was accompanied by an increased incidence of germ cell apoptosis. The acridine orange assay revealed a significant increase in sperm with abnormal DNA integrity profiles in the 1x CHOP group. Despite effects on germ cell number and quality, CHOP-exposed rats remained fertile. However, a 50% decrease in live fetuses was observed in litters sired by 1x CHOP-treated males due to a significant increase in both pre-implantation and postimplantation losses; postimplantation loss was also elevated among litters sired by 2/3x CHOP-treated males. Thus, CHOP treatment affected both the quantity and quality of male germ cells; conceptal loss is a sensitive measure of the integrity of the male genome.