双酚A对诱导型一氧化氮合酶基因缺失鼠卵母细胞染色体不分离的影响

Effect of Bisphenol A on the Oocyte Chromosome Non-disjunction in i Nos^(-/-) Mice

目的:研究双酚A(bisphenol A,BPA)暴露对诱导型一氧化氮合酶(inducible nitric oxide synthase,i Nos)基因缺失(i Nos-/-)的实验鼠卵母细胞染色体不分离的影响。方法:给野生型雌鼠(i Nos+/+)和i Nos基因敲除(i Nos-/-)的雌鼠强饲(oral gavage)BPA 100μg/(kg·d)或200μg/(kg·d)连续13 d。结果:在i Nos+/+组实验鼠卵细胞MⅡ期非整倍体卵母细胞数量没有显著增加。在i Nos-/-组实验鼠卵母细胞染色体分离错误和染色单体提前分离增加。基因表达的特性表明polo样激酶1(PLK1)和RAN GTPase蛋白(RAN)水平在i Nos-/-组实验鼠卵细胞的细胞周期和纺锤体的调控大幅下降。结论:i Nos可能通过维持蛋白PLK1和蛋白RAN在哺乳类动物卵细胞稳定地表达,直接或间接地保护染色体减数分裂中精确分离;低水平的BPA暴露可能引起具有i Nos-/-遗传背景卵细胞染色体畸变。

Objective： To explore the effects of bisphenol A （bisphenol A, BPA） on the oocyte chromosome non-disjunction in iNos4- mice. Methods：Female iNos mice and iNos-/- mice, aged 20-22 days, were treated with BPA （100 or 200 μg/kg body weight per day） by intragastric administration for 13 days. The isopyknic corn oil was used as control. Results：In the iNos^＋/＋ mice groups, the numbers of aneuploidy oocytes at metaphase M Ⅱ were not increased by BPA treatment. Interestingly, the numbers of those oocytes with the error- prone chromosome segregation and the precocious chromatid separation in the iNos 4- mice groups were significantly increased by BPA treatment. Meanwhile, the expressions of polo-like kinase-1 （PLK1） and RAN GTPase （RAN） in oocytes of the iNos4- mice were significantly down-regulated by BPA treatment. Conclusions： iNos has a direct or indirect protection against the faithful chromosome segregation during meiosis, possibly by maintaining stable expression of PLK1 and RAN in mammalian oocytes. BPA exposure at low level may induce chromosomal aberrations in those oocytes of iNos4- mice.