Somatic and reproductive development in pre-pubertal mice treated with cyclophosphamide and subsequent estrogen replacement

摘要

We tested the hypothesis that chemotherapy would prevent the expected pubertal development of uterus, ovaries, and long bones, and that estrogen replacement subsequent to treatment with chemotherapy would restore uterine and bone development to expected sizes. Pre-pubertal female C57BL/6J mice (n = 78) were assigned to receive placebo (controls), 200 mg/kg (group A), or 120 mg/kg (group B) of cyclophosphamide (CTX) on postnatal day 18. Mice were subsequently randomized to receive estradiol placebo or long-release estradiol pellet insertion on day 22 (early estradiol dose), day 45 (mid estradiol dose), or day 67 (late estradiol dose) of life. Body weight and length, uterine and ovarian weight, and right femur length and weight were measured. Mice treated with CTX had shorter and lighter femurs and lighter ovaries than controls (13.46 cm ± 1.51 cm vs. 15.00 cm ± 1.10 cm, 57.70 mg ± 9.71 mg vs. 65.30 mg ± 3.68 mg, and 5.16 mg ± 3.00 mg vs. 10.05 mg ± 2.31 mg, respectively; p 0.05). Mice receiving estrogen replacement had a larger average body weight, BMI, and uterine weight than those that received placebo estrogen (19.56 g ± 1.82 g vs. 18.10 g ± 2.08 g, 26.53 g/cm2 ± 2.91 g/cm2 vs. 23.47 g/cm2 ± 3.06 g/cm2, 101.19 mg ± 41.69 mg vs. 50.00 mg ± 9.49 mg, respectively; p 0.05). Cyclophosphamide treatment in pre-pubertal mice negatively affected femur and reproductive development. Estrogen treatment restored expected uterine development by maturity, regardless of the timing of administration. However, there was no similar recovery of femur length and bone mass was only partially recovered.