抗真菌药物影响生殖细胞发育机理的研究

THE REGULATING MECHANISM OF ANTI FUNGICIDES ON MOUSE OOCYTE DEVELOPMENT

目的 :探讨抗真菌药物对促性腺激素诱导的卵母细胞成熟的机理。方法 :用小鼠卵母细胞体外培养模型 ,将小鼠卵母细胞培养在含有次黄嘌呤 (HX ,卵母细胞成熟抑制物 )的培养液中 ,观察促卵泡生成素 (FSH)、两性霉素B、酮康唑对卵母细胞减数分裂恢复的影响。结果 :①FSH(10～ 2 0 0IU/L)显著刺激卵丘 卵母细胞复合体 (CEO)克服HX的抑制而恢复减数分裂 ,该作用具有剂量依赖性 (P <0 .0 5 ) ;②两性霉素B(0 .0 0 2 5～ 2 5 0 μg/L)也能够明显诱导CEO恢复减数分裂 ,其作用具有剂量依赖性 (P <0 .0 5 ) ;③酮康唑 (10 -7～ 10 -3 mol/L)剂量依赖性抑制FSH(5 0IU/L)诱导的卵母细胞减数分裂恢复 (P <0 .0 5 ) ,但并不影响卵母细胞的自发成熟 (P >0 .0 5 )。结论 :两性霉素B、酮康唑对卵母细胞减数分裂的恢复具有影响 ,其机理可能在于影响促性腺激素诱导的、卵丘细胞分泌的甾醇类物质 (MAS)

Aim: To study the mechanism of the effect of gonadotropin induced oocyte maturation.Methods:mouse oocytes were cultured in HX medium, and the effects of amphotericin B and ketoconazole on resumption of meiosis of mouse oocyte were examined. Results:① FSH(10～200 IU/L) induced a dose dependent manner of oocytes maturation in CEO. A maximum increase in GVBD was observed with 25～50 IU/L FSH. ②Amphotericin tericim B (0.025～2.5 μg/L)caused significant increases in GVBD in CEO, which mimicked the function of FSH.③Ketoconazole (10 -7 ～10 -3 mol/L) inhibited the effect of FSH on resumption of meiosis, but no effect on oocyte spontaneous maturation. Conclution: Amphotericin B and ketoconazole are able to affect mouse oocyte maturation, and indicates that they have a regulation on FSH induced synthesis of meiosis activating sterol.