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Effects of the chemotherapeutic agents for non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), on the male rat reproductive system and progeny outcome.
- Source :
-
Journal of andrology [J Androl] 2007 Jul-Aug; Vol. 28 (4), pp. 578-87. Date of Electronic Publication: 2007 Apr 04. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Apoptosis drug effects
Cyclophosphamide administration & dosage
Doxorubicin administration & dosage
Female
Humans
In Situ Nick-End Labeling
Lymphoma, Non-Hodgkin drug therapy
Male
Nucleic Acid Denaturation drug effects
Prednisone administration & dosage
Pregnancy
Pregnancy Outcome
Rats
Rats, Sprague-Dawley
Testis drug effects
Testosterone blood
Vincristine administration & dosage
Antineoplastic Combined Chemotherapy Protocols pharmacology
Cyclophosphamide pharmacology
Doxorubicin pharmacology
Testis pathology
Vincristine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0196-3635
- Volume :
- 28
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of andrology
- Publication Type :
- Academic Journal
- Accession number :
- 17409468
- Full Text :
- https://doi.org/10.2164/jandrol.106.002428