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.
出处
《癌变．畸变．突变》
CAS
CSCD
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)
关键词
多柔比星
腔前卵泡
生殖毒性
卵丘-卵母细胞复合体
doxorubicin
preantral follicles
reproductive toxicity
cumulus-oocyte cell complexes
