INCREASED POSTIMPLANTATION LOSS AND MALFORMATIONS AMONG THE F2 PROGENY OF MALE-RATS CHRONICALLY TREATED WITH CYCLOPHOSPHAMIDE
INCREASED POSTIMPLANTATION LOSS AND MALFORMATIONS AMONG THE F2 PROGENY OF MALE-RATS CHRONICALLY TREATED WITH CYCLOPHOSPHAMIDE
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DOI：
10.1002/tera.1420450612
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发表时间：
1992-06-01
期刊：
影响因子：
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通讯作者：
ROBAIRE, B
中科院分区：
文献类型：
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作者：
HALES, BF;CROSMAN, K;ROBAIRE, B
给予雄性大鼠环磷酰胺，导致子代着床前和着床后丢失增加，以及畸形和生长迟缓胎仔数量增加。本研究的目的是确定长期父系环磷酰胺暴露的不良反应是否可传递给下一代，即F2子代。成年雄性大鼠每天用盐水或环磷酰胺（3.4或5.1 mg/kg）灌胃给药4周或18周，然后交配。将每个处理组（F1代）中的雄性和雌性后代随机交配。在妊娠第20天处死所得妊娠雌性动物，以评价F2代的子代结局。在其父亲接受5.1 mg/kg/天剂量环磷酰胺给药的组的后代中，着床后丢失显著增加。暴露于5.1 mg/kg/天剂量的环磷酰胺也导致F2代每窝平均胎仔体重显著降低，畸形胎仔数量显著增加。在F2子代中观察到的畸形包括睁眼、脐膨出、全身水肿、并指畸形、多指畸形和侏儒症。因此，暴露于环磷酰胺的父亲确实会导致一个特定的和遗传的改变，在生育能力的幸存的“明显正常”的F1代。有趣的是，雄性大鼠暴露于环磷酰胺的不良后果在F2代中与先前报道的F1后代相似。
Cyclophosphamide, administered to the male rat, produces increased pre- and postimplantation loss in the progeny as well as an increase in the numbers of malformed and growth retarded fetuses. The purpose of this study was to determine whether the adverse effects of chronic paternal cyclophosphamide exposure are transmissible to the next generation, the F2 progeny. Adult male rats were treated by gavage daily with saline or with cyclophosphamide (3.4 or 5.1 mg/kg) for 4 or 18 weeks and mated. The male and female offspring in each treatment group (F1 generation) were randomly mated. The resulting pregnant females were killed on day 20 of gestation to evaluate progeny outcome in the F2 generation. There was a significant increase in postimplantation loss among the offspring of the group whose fathers had been treated with cyclophosphamide at a dose of 5.1 mg/kg/day. Exposure to a dose of 5.1 mg/kg/day of cyclophosphamide also resulted in an F2 generation with a significantly decreased mean fetal weight per litter and a significant increase in the number of malformed fetuses. The malformations observed among the F2 progeny included open eyes, omphalocele, generalized edema, syndactyly, gigantism, and dwarfism. Thus, exposure of the father to cyclophosphamide does result in a specific and heritable alteration in the fertility of the surviving "apparently normal" F1 progeny. Interestingly, the adverse consequences of exposure of male rats to cyclophosphamide are similar in the F2 generation to those previously reported for the F1 progeny.