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先前母体使用环磷酰胺(Cp)进行化疗会导致植入前小鼠胚胎出现染色体数目异常。

Previous maternal chemotherapy by cyclophosphamide (Cp) causes numerical chromosome abnormalities in preimplantation mouse embryos.

作者信息

Barekati Zeinab, Gourabi Hamid, Valojerdi Mojtaba Rezazadeh, Yazdi Poopak Eftekhari

机构信息

Biology Department, Faculty of Basic Science and Research Branch, Islamic Azad University, Tehran, Iran.

出版信息

Reprod Toxicol. 2008 Nov-Dec;26(3-4):278-81. doi: 10.1016/j.reprotox.2008.09.014. Epub 2008 Oct 15.

Abstract

This study investigated the consequences of maternal cyclophosphamide treatment on fertilization rate, development and chromosomal integrity of embryos. It also evaluated efficiency of two methods of classic and metaphase induction for chromosomes assessment. Two different groups of NMRI mice 2-3 weeks and 6-7 weeks were injected intraperitonealy with 75 mg cyclophosphamide/kg. Six weeks later, oocytes were recovered, fertilized and incubated for 3 days in 5% CO(2) in air. Eight to 10 cell stage embryos were subjected to chromosomal study. Cyclophosphamide in both experimental groups reduced the oocyte fertilization rate and in the 6-7 weeks group it was significantly lower compared with control group (P<0.01). Also there was a reduction in 8-cell stage embryos formation from 48 to 72 h post-fertilization in both treated groups (P<0.05). Aneuploidy increased in the treatment groups compared with controls, which in the older group was significant (P<0.001). The success rate of the classic method to analyze metaphase plates was 30.1% and the success rate of heterokaryons formation with analyzable chromosomes was 67.8% in the metaphase induction method. In regards to the adverse effects of cyclophosphamide on fertilization rate, embryo development and chromosomal integrity of the mouse embryos, using Preimplantation Genetic Diagnosis in addition to Assisted Reproductive Technique is suggested.

摘要

本研究调查了母体环磷酰胺治疗对胚胎受精率、发育及染色体完整性的影响。同时评估了经典方法和中期诱导法两种染色体评估方法的效率。将两组不同的NMRI小鼠(2 - 3周龄和6 - 7周龄)腹腔注射75 mg环磷酰胺/千克。六周后,回收卵母细胞,进行受精,并在含5%二氧化碳的空气中孵育3天。对8至10细胞期胚胎进行染色体研究。两个实验组中的环磷酰胺均降低了卵母细胞受精率,且6 - 7周龄组与对照组相比显著降低(P<0.01)。两个处理组在受精后48至72小时8细胞期胚胎形成均减少(P<0.05)。与对照组相比,处理组非整倍体增加,在年龄较大的组中差异显著(P<0.001)。经典方法分析中期板的成功率为30.1%,中期诱导法中可分析染色体的异核体形成成功率为67.8%。鉴于环磷酰胺对小鼠胚胎受精率、胚胎发育及染色体完整性的不良影响,建议在辅助生殖技术基础上联合应用植入前遗传学诊断。

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