Santos Eduarda M, Paull Gregory C, Van Look Katrien J W, Workman Victoria L, Holt William V, van Aerle Ronny, Kille Peter, Tyler Charles R
School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, UK.
Aquat Toxicol. 2007 Jun 15;83(2):134-42. doi: 10.1016/j.aquatox.2007.03.019. Epub 2007 Mar 30.
Environmental oestrogens are widespread in the aquatic environment and cause alterations in sexual development and function in vertebrates. The molecular pathways underpinning these effects, however, remain poorly understood. In this study, we aimed at generating a mechanistic understanding of the disruptive effects of exposure to environmentally relevant concentrations of 17 alpha-ethinyloestradiol (EE(2)) on reproduction in zebrafish, by anchoring the transcriptomic alterations induced with the physiological consequences of exposure. Breeding colonies of zebrafish were exposed for a 21-day period to three concentrations of EE(2) (0.05, 0.5 and 5 ng/L) and the gonadal transcriptomic alterations induced (determined using a 17,000 oligonucleotide microarray) were analysed together with physiological effects seen on reproductive output of both males and females. Exposure to 5 ng EE(2)/L resulted in reproductive impairment characterised by a decrease in egg production, alterations in sperm quality and reduced fertilisation success. The effects seen were associated with altered expression of 114 and 131 genes in the gonads of males and females, respectively. The biological processes most affected by the exposure were protein metabolism in males and mitochondria organisation and biogenesis in females. Genes involved in the regulation of cell cycle progression, the ubiquitin system and glutathione peroxidase were affected by the EE(2) exposure and associated with the changes observed in gamete quality in both genders. In summary, we demonstrated that EE(2) exposure compromised the reproductive health of breeding zebrafish at environmentally relevant concentrations. The molecular mechanisms mediating some of these effects were identified and included those impacting processes central to gametogenesis in both males and females.
环境雌激素广泛存在于水生环境中,并会导致脊椎动物性发育和功能的改变。然而,支撑这些影响的分子途径仍知之甚少。在本研究中,我们旨在通过将暴露诱导的转录组变化与暴露的生理后果联系起来,深入了解环境相关浓度的17α-乙炔雌二醇(EE(2))对斑马鱼繁殖的破坏作用。将斑马鱼繁殖群体暴露于三种浓度的EE(2)(0.05、0.5和5纳克/升)中21天,分析诱导的性腺转录组变化(使用17000寡核苷酸微阵列测定),并结合对雄性和雌性繁殖输出的生理影响进行分析。暴露于5纳克EE(2)/升会导致繁殖受损,表现为产卵量减少、精子质量改变和受精成功率降低。观察到的这些影响分别与雄性和雌性性腺中114个和131个基因的表达改变有关。受暴露影响最大的生物学过程在雄性中是蛋白质代谢,在雌性中是线粒体组织和生物发生。参与细胞周期进程调控、泛素系统和谷胱甘肽过氧化物酶的基因受到EE(2)暴露的影响,并与两性配子质量的变化有关。总之,我们证明了在环境相关浓度下,EE(2)暴露会损害繁殖斑马鱼的生殖健康。我们确定了介导其中一些影响的分子机制,包括那些影响雄性和雌性配子发生核心过程的机制。