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多柔比星对体外培养小鼠腔前卵泡发育的影响

 婷,李 雷,王忠辉,严建燕,潘 琦,刘向云,孙祖越*   

  1. ( 上海市计划生育科学研究所药理毒理室,中国生育调节药物毒理检测中心,上海 200032 )
  • 收稿日期:2013-05-16 修回日期:2013-06-26 出版日期:2013-09-30 发布日期:2013-09-30
  • 通讯作者: 孙祖越,E-mail:Sunzy64@163.com
  • 作者简介:张 婷 (1974- ),女,湖北省武汉市人,博士,研究方向:生殖毒性。E-mail:fuzzyting@163.com
  • 基金资助:

    “重大新药创制”科技重大专项“十二五”计划 (2011ZX09301-005)

Effect of doxorubicin on the development of cultured preantral follicles in mice

ZHANG Ting,LI Lei,WANG Zhong-hui,YAN Jian-yan,PAN Qi,LIU Xiang-yun,SUN Zu-yue*   

  1. (Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Shanghai 200032, China)
  • Received:2013-05-16 Revised:2013-06-26 Online:2013-09-30 Published:2013-09-30
  • Contact: SUN Zu-yue,E-mail:Sunzy64@163.com

摘要:

目的: 利用雌性ICR小鼠腔前卵泡体外培养方法观察多柔比星对卵泡发育的影响,对多柔比星卵巢毒性机制进行初步探讨。方法:取12~14日龄的雌性ICR小鼠卵巢的腔前卵泡进行原代培养,在培养的第2、6和11天,分别用不同浓度的多柔比星 (0.4、0.8、1.6和3.2 μg/mL)染毒24 h后继续培养。通过测量卵泡的大小、存活率和卵丘-卵母细胞复合体 (cumulus-oocyte cell complexes,COCs)的排出率来判定多柔比星对腔前卵泡发育的影响。 结果:在实验所设置的剂量范围内,与对照组比较,多柔比星在1.6和3.2 μg/mL浓度下能明显抑制雌性ICR小鼠卵巢腔前卵泡的发育 (P<0.05),降低卵泡的存活率 (P< 0. 05),并抑制COCs的排出 (P<0.05),且呈一定的剂量效应关系。结论:多柔比星可抑制腔前卵泡的发育,降低卵泡的存活率,抑制COCs的排出,从而引起卵巢毒性,产生卵巢功能障碍。

关键词:  多柔比星v腔前卵泡, 生殖毒性, 卵丘-卵母细胞复合体

Abstract:

 OBJECTIVE: To study the effect of doxorubicin on the development of cultured preantral follicles in female ICR mice and explore the preliminary mechanism of ovarian toxicity. METHODSCultured ovarian preantral follicles taken from day 12-14 female ICR mice were treated for 24 h with various concentrations of doxorubicin (0.4,0.8,1.6 and 3.2 μg/mL) on cultured day 2,6 or 11. Following the treatment,follicles were cultured to the endpoint. Follicle diameter measurement,follicle viability and cumulus-oocyte cell complexes (COCs) ovulation rate were used to confirm the effect on preantral follicle development. RESULTS:Compared to the control group, doxorubicin at the concentrations of 1.6 and 3.2 μg/mL could inhibit ovarian preantral follicle development (P<0.05), decrease the viability (P<0.05) and inhibit COCs ovulation (P<0.05) in a concentration-dependent manner.  CONCLUSIONDoxorubicin could significantly inhibit the development of ovarian preantral follicles,decrease the viability and inhibit COCs ovulation,which could induce ovarian toxicity and dysfunction.

Key words: doxorubicin, preantral follicles, reproductive toxicity, cumulus-oocyte cell complexes