多柔比星对体外培养小鼠腔前卵泡发育的影响  

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

作　　者：张婷[1] 李雷[1] 王忠辉[1] 严建燕[1] 潘琦[1] 刘向云[1] 孙祖越[1] 

机构地区：[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

出　　处：《癌变．畸变．突变》2013年第5期360-364,368,共6页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金："重大新药创制"科技重大专项"十二五"计划(2011ZX09301-005)

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11X，分别用不同浓度的多柔比星（0．4、0．8、1．6和3．2μg／mL）染毒24hA继续培养。通过测量卵泡的大小、存活率和卵丘一卵母细胞复合体fcumulus—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3．2μg／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卯泡的发育，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。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. METHODS ： Cultured 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 3.2μg/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 3.2μ g/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. CONCLUSION： Doxorubicin could significantly inhibit the development of ovarian preantral follicles, decrease the viability and inhibit COCs ovulation, which could induce ovarian toxicity and dysfunction.

关 键 词：多柔比星 腔前卵泡 生殖毒性 卵丘-卵母细胞复合体 

分 类 号：R394.6[医药卫生—医学遗传学]