Reproductive toxicity of cyclophosphamide in the C57BL/6N mouse: 2. Effects on uterine structure and function.
Cyclophosphamide-induced uterine weight loss was evaluated to determine whether it was a function of primary toxicity to the uterus or a secondary response to ovarian toxicity, that is, antral follicle destruction. C57BL/6N mice treated with cyclophosphamide exhibited a reduction in uterine weight concurrent with a decrease in plasma estradiol (E2) concentrations, thereby indicating toxicity to the ovary. However, when E2 concentrations recovered, uterine weight still remained depressed, suggesting that cyclophosphamide also impaired uterine function. Further investigation revealed that cyclophosphamide altered the normal uterotropic response to E2, significantly diminishing the uterine weight gain associated with E2 treatment. We conclude that effects of cyclophosphamide on the uterus involve two components: 1) decreased uterine weight in response to decreased plasma E2 resulting from ovarian toxicity, and 2) an altered response to E2 due to direct uterine toxicity.
Plowchalk
D R
DR
Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock.
Meadows
M J
MJ
Mattison
D R
DR
D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects*; D013997:Time Factors; D014591:Uterine Diseases / Q000139:chemically induced*; D014599:Uterus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology
D004958:Estradiol; D003520:Cyclophosphamide