REVERSIBILITY OF THE EFFECTS OF CHRONIC PATERNAL EXPOSURE TO CYCLOPHOSPHAMIDE ON PREGNANCY OUTCOME IN RATS

被引:22
作者
HALES, BF
ROBAIRE, B
机构
[1] MCGILL UNIV,CTR STUDY REPROD,MONTREAL H3G 1Y6,QUEBEC,CANADA
[2] MCGILL UNIV,DEPT OBSTET & GYNECOL,MONTREAL H3G 1Y6,QUEBEC,CANADA
来源
MUTATION RESEARCH | 1990年 / 229卷 / 02期
基金
英国医学研究理事会;
关键词
Cyclophosphamide; Male-mediated toxicity; Post-implanation loss; Pre-implantation loss; Pregnancy outcome in rats; Reversal;
D O I
10.1016/0027-5107(90)90087-K
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Low-dose chronic treatment of the male rat with the antitumor drug cyclophosphamide causes a time-and dose-dependent increase in pre- and post-implantation loss in the untreated females to which he is mated. The objective of the present was to determine whether such effects are reversed, and if so at what time after cessation of drug treatment. Adult male Sprague-Dawley rats were gavage fed daily, 6 time per week for 9 weeks, with saline (control) or with 1 of 3 doses of cyclophosphamide, 1.4, 3.4 or 5.1 mg/kg/day. After the 9 weeks of treatment and at 2-week intervals thereafter, each male was mated with 2 females in proestrus. The female were caesarian sectioned 20 days later and pregnancy outcome assessed. After 9 weeks of drug treatment, pre-implantation loss increased more than 3-fold from 6% in the control group to 21% in the 5.1 mg/kg/day cyclophosphamide treatment group. Post-implantation loss increased in a dose dependent fashion from 5% in the control group to 74% in the 5.1 mg/kg/day cyclophosphamide treatment group. Pre-implantation loss rapidly decreased ceasstion of treatment with cyclophosphamide: within 2 weeks it had returned to within the control range. Within just 2 weeks after termination of drug treatment in the 5.1 mg/kg/day cyclophosphamide treatment group, post-implantation loss decreased by half to 44%; it had decreased to 11% by 4 weeks and then was maintained at 4-6% thereafter. In the 3.4 mg/kg/day cyclophosphamide treatment group, post-implantation loss returned to the control range by 4 weeks. Thus, the effects of paternally administered cyclophosphamide on progency outcome are reversible. The timing of reversal suggests that the effects on pre-implantation loss are due to a drug effect on spermatozoa either in the epididymis or near the time of spermiation while these on post-implantation loss are due to an additional effect on spermatids in the seminiferous tubules. © 1990.
引用
收藏
页码:129 / 134
页数:6
相关论文
共 24 条
  • [1] ADAMS PM, 1981, SCIENCE, V211, P80, DOI 10.1126/science.7444453
  • [2] CYTOGENETIC TOXICITY OF CYCLOPHOSPHAMIDE AND ITS METABOLITES INVITRO
    AU, W
    SOKOVA, OI
    KOPNIN, B
    ARRIGHI, FE
    [J]. CYTOGENETICS AND CELL GENETICS, 1980, 26 (2-4): : 108 - 116
  • [3] CYCLOPHOSPHAMIDE IN THE MALE-RAT - BEHAVIORAL-EFFECTS IN THE ADULT OFFSPRING
    AUROUX, M
    DULIOUST, E
    [J]. BEHAVIOURAL BRAIN RESEARCH, 1985, 16 (01) : 25 - 36
  • [4] AUROUX MR, 1986, J ANDROL, V7, P378
  • [5] CLIFTON DK, 1983, J ANDROL, V4, P387
  • [6] DUNNET CW, 1967, STATISTICS ENDOCRINO, P79
  • [7] INDUCTION OF DOMINANT LETHAL MUTATIONS BY ALKYLATING AGENTS IN MALE MICE
    EHLING, UH
    CUMMING, RB
    MALLING, HV
    [J]. MUTATION RESEARCH, 1968, 5 (03): : 417 - &
  • [8] GIBSON JE, 1968, CANCER RES, V28, P475
  • [9] GROWTH AND DEVELOPMENT OF CHILDREN BORN TO PATIENTS AFTER CANCER-THERAPY
    GULATI, SC
    VEGA, R
    GEE, T
    KOZINER, B
    CLARKSON, B
    [J]. CANCER INVESTIGATION, 1986, 4 (03) : 197 - 205