title: Somatic and reproductive outcomes in mice treated with cyclophosphamide in pre-pubertal age.
abstract: Disruption in the normal timing of female puberty, such as in pre-pubertal cancer treatments, can cause abnormal somatic development. We sought to evaluate the impact of cyclophosphamide (CTX) on the somatic, uterine, and ovarian, development of pre-pubertal mice. Pre-pubertal (day 18 of life) C57BL/6J female mice were randomized to receive placebo (group 1A and 1B), 200 mg/kg CTX (group 2A), or 120 mg/kg CTX (group 2B). Mice were euthanized on day 56 (A groups) or 95 (B groups) of life. Body weight and length, uterine and ovarian weight and right femur length and weight were measured, and ovarian insufficiency was assessed. Data were analyzed using ANOVA and t-test. Body weight and length did not differ among groups at time of euthanasia. The femur was shorter and weighed less in mice treated with CTX than in controls. Uterine weight was lower in group 2B than 1B (46.1 mg, 95% CI: 42.9-49.4, vs. 62.2 mg, 95% CI: 58.5-65.8, respectively; p = 0.005) and was lower in mice that developed ovarian insufficiency than in mice that did not (p < 0.05). Ovarian weight was lower in mice treated with CTX, regardless of whether they developed ovarian insufficiency. Even with no observable effect on adult body length and weight, CTX treatment in pre-pubertal mice appears to negatively affect femur, uterine, and ovarian development. However, uterine development seems to be dependent on the hormonal status created by CTX more than on its direct effect.
authors.affiliation: University of Tennessee Health Science Center, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Tennessee, Memphis, Tennessee 38163, USA. ldetti@uthsc.edu
authors.forename: Laura
authors.initials: L
authors.lastname: Detti
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Martin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Natalia
authors.initials: N
authors.lastname: Schlabritz-Loutsevich
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Williams
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Uhlmann
mesh_terms: D000367:Age Factors; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000187:drug effects / Q000254:growth & development; D005640:Follicle Stimulating Hormone / Q000097:blood; D007247:Infertility, Female / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000503:physiopathology; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment; D012307:Risk Factors; D046468:Sexual Development; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone