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Paternal exposure to environmental 17-alpha-ethinylestradiol concentrations modifies testicular transcription, affecting the sperm transcript content and the offspring performance in zebrafish
Aquatic Toxicology ( IF 4.1 ) Pub Date : 2017-09-28 , DOI: 10.1016/j.aquatox.2017.09.025
David G. Valcarce , Elena Vuelta , Vanesa Robles , Maria Paz Herráez

The synthetic estrogen 17-α-ethinylestradiol (EE2), a major constituent in contraceptive pills, is an endocrine disrupting chemical (EDC) present in the aquatic environment at concentrations of ng/L. Developmental exposure to these low concentrations in fish can induce several disorders. Zebrafish (Danio rerio) is a perfect organism for monitoring the effects of environmental contaminants. Our hypothesis is that changes promoted by EE2 in the germ line of male adults could be transmitted to the unexposed progeny. We exposed male zebrafish to 2.5, 5 and 10 ng/L of EE2 during spermatogenesis and mated them with untreated females. Detailed progeny development was studied concentrating to survival, hatching and malformations. Due to the high incidence of lymphedemas within larvae, we performed qPCR analysis of genes involved in lymphatic development (vegfc and vegfr3) and endothelial cell migration guidance (cxcr4a and cxcl12b). Estrogen receptor (ER) transcript presence was also evaluated in sperm, testis and embryos. Progenies showed a range of disorders although at a low incidence: skeletal distortions, uninflated swimbladder, lymphedema formation, cartilage deformities and otolith tethering. Swimming evaluation revealed less active locomotion. All these processes are related to pathways involving ERs (esr1, esr2a and esr2b). mRNA analysis revealed that environmental EE2 causes the up-regulation of esr1 an esr2b in testis and the increase of esr2b transcripts in sperm pointing to a link between lymphedema in embryos and ER expression impairment. We demonstrate that the effects induced by environmental toxicants can be paternally inherited and point to the changes on the sperm transcriptome as the responsible mechanism.



中文翻译:

父亲暴露于环境17-α-乙炔雌二醇浓度会改变睾丸的转录,从而影响斑马鱼的精子转录物含量和后代性能

合成雌激素17-α-炔雌醇(EE2)是避孕药的主要成分,是水生环境中浓度为ng / L的内分泌干扰化学物质(EDC)。发育中暴露于鱼类中的这些低浓度会导致多种疾病。斑马鱼(斑马鱼)是监测环境污染物影响的理想生物。我们的假设是,EE2促进的成年男性生殖细胞系的变化可能会传播给未暴露的后代。在精子发生过程中,我们将雄性斑马鱼暴露于2.5、5和10 ng / L的EE2中,并与未经处理的雌性交配。研究了详细的后代发育,集中于生存,孵化和畸形。由于幼虫内淋巴水肿的发生率很高,我们对涉及淋巴发育的基因(vegfcvegfr3)和内皮细胞迁移指导(cxcr4acxcl12b)进行了qPCR分析)。还评估了精子,睾丸和胚胎中雌激素受体(ER)转录本的存在。后代虽然发病率低,但显示出一系列疾病:骨骼变形,游泳膀胱未充气,淋巴水肿形成,软骨畸形和耳石栓系。游泳评估显示主动运动较少。所有这些过程都与涉及ER(esr1esr2aesr2b)的途径有关。mRNA分析显示环境EE2引起睾丸中esr1esr2b的上调以及esr2b的增加精子中的转录本,指向胚胎淋巴水肿与ER表达受损之间的联系。我们证明环境毒物诱导的影响可以是父系遗传,并指出精子转录组的变化是其负责任的机制。

更新日期:2017-09-28
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