Abstract:
In response to the EU cosmetics directive regulation and REACH legislation which encourage cell culture methods in order to reduce or replace the use of animals in toxicology studies, we settled the culture of prepubertal domestic cat seminiferous tubules in our validated BioAlter® model, usually used with prepubertal rat, called here BioAlter®-rat, by opposition to BioAlter®-cat settled here. We carried out a comparative study on the effects of 3 testicular toxicants, 1,3-dinitrobenzene at 60 μM, 2-methoxyacetic acid at 2.5 mM and carbendazim at 50 nM or 500 nM in both BioAlter®-cat and BioAlter®-rat over a 3-week culture period. Sertoli cell or each germ cell populations as well as the levels of Sertoli cell or germ cell specific mRNAs were studied. The harmful effects of the 3 toxicants on pre-meiotic, meiotic and post-meiotic cell numbers and on Sertoli or germ cell specific mRNAs were clearly observed in the two species, even if there might be some small differences in the intensity of the effects on some of the studied parameters. Hence, BioAlter®-cat might be a solution to the requirements of the EU cosmetics directive and REACH legislation for male reproductive toxicology studies.
摘要:
为了响应欧盟化妆品指令法规和REACH法规,这些法规鼓励细胞培养方法,以减少或替代动物在毒理学研究中的使用,我们在经过验证的BioAlter®模型中解决了青春期前家猫生精小管的培养,通常与青春期前大鼠一起使用,这里叫做BioAlter®-rat,反对BioAlter®-cat在这里定居。我们对3种睾丸毒物的作用进行了比较研究,60μM的1,3-二硝基苯,在3周的培养期内,在BioAlter®-cat和BioAlter®-大鼠中的2-甲氧基乙酸和多菌灵在50nM或500nM。研究了支持细胞或每个生殖细胞群体以及支持细胞或生殖细胞特异性mRNA的水平。3种有毒物质对减数分裂前的有害影响,在这两个物种中清楚地观察到减数分裂和减数分裂后的细胞数量以及Sertoli或生殖细胞特异性mRNA,即使对某些研究参数的影响强度可能存在一些小差异。因此,BioAlter®-cat可能是欧盟化妆品指令和REACH法规对男性生殖毒理学研究的要求的解决方案。