Endocrine disrupting chemicals (EDCs) can induce abnormalities in organisms via alteration of molecular pathways and subsequent disruption of endocrine functions. Bisphenol A (BPA) and 17α-ethinylestradiol (EE2) are ubiquitous EDCs in the environment. Many aquatic organisms, including fish, are often exposed to varying concentrations of BPA and EE2 throughout their lifespan. Both BPA and EE2 can activate estrogenic signaling pathways and cause adverse effects on reproduction via alteration of pathways associated with steroidogenesis. However, transcriptional pathways that are affected by chronic exposure to these two ubiquitous environmental estrogens during embryonic, larval, and juvenile stages are not clearly understood. In the present study, we examined transcriptional alterations in the testis of medaka fish (Oryzias latipes) chronically exposed to a low concentration of BPA or EE2. Medaka were exposed to BPA (10 μg/L) or EE2 (0.01 μg/L) from 8 h post-fertilization (as embryos) to adulthood 50 days post fertilization (dpf), and transcriptional alterations in the testis were examined by RNA sequencing (RNA-seq). Transcriptomic profiling revealed 651 differentially expressed genes (DEGs) between BPA-exposed and control testes, while 1475 DEGs were found between EE2-exposed and control testes. Gene ontology (GO) analysis showed a significant enrichment of “intracellular receptor signaling pathway”, “response to steroid hormone” and “hormone-mediated signaling pathway” in the BPA-induced DEGs, and of “cilium organization”, “microtubule-based process” and “organelle assembly” in the EE2-induced DEGs. Pathway analysis showed significant enrichment of “integrin signaling pathway” in both treatment groups, and of “cadherin signaling pathway”, “Alzheimer disease-presenilin pathway” in EE2-induced DEGs. Single nucleotide polymorphism (SNP) and insertion-deletion (Indel) analysis found no significant differences in mutation rates with either BPA or EE2 treatments. Taken together, global gene expression differences in testes of medaka during early stages of gametogenesis were responsive to chronic BPA and EE2 exposure.

内分泌干​​扰化学品 (EDC) 可通过改变分子途径和随后破坏内分泌功能来诱导生物体异常。双酚 A (BPA) 和 17α-炔雌醇 (EE2) 是环境中普遍存在的 EDC。许多水生生物，包括鱼类，在其整个生命周期中经常暴露于不同浓度的 BPA 和 EE2。BPA 和 EE2 都可以激活雌激素信号通路，并通过改变与类固醇生成相关的通路对生殖产生不利影响。然而，在胚胎、幼虫和幼年阶段长期暴露于这两种普遍存在的环境雌激素影响的转录途径尚不清楚。在本研究中，我们检查了青鳉鱼睾丸的转录改变（稻米) 长期暴露于低浓度的 BPA 或 EE2。从受精后 8 小时（作为胚胎）到受精后 50 天（dpf）的成年期（dpf），青鳉暴露于 BPA（10 μg/L）或 EE2（0.01 μg/L），并通过 RNA 测序检查睾丸中的转录改变（RNA序列）。转录组分析揭示了 BPA 暴露和对照睾丸之间的 651 个差异表达基因 (DEG)，而 EE2 暴露和对照睾丸之间发现了 1475 个差异表达基因 (DEG)。基因本体（GO）分析显示，BPA诱导的DEGs中“细胞内受体信号通路”、“对类固醇激素的反应”和“激素介导的信号通路”以及“纤毛组织”、“基于微管的信号通路”显着富集。 EE2 诱导的 DEG 中的过程”和“细胞器组装”。通路分析显示，两个治疗组中“整合素信号通路”显着富集，EE2 诱导的 DEG 中“钙粘蛋白信号通路”、“阿尔茨海默病-早老素通路”显着富集。单核苷酸多态性 (SNP) 和插入缺失 (Indel) 分析发现 BPA 或 EE2 处理的突变率没有显着差异。总之，在配子发生早期，青鳉睾丸中的全局基因表达差异对慢性 BPA 和 EE2 暴露有反应。