The brominated flame retardant, 1,2,5,6-tetrabromocyclooctane (TBCO), has been shown to decrease fecundity in Japanese medaka (Oryzias latipes) and there is indirect evidence from analysis of the transcriptome and proteome that this effect might be due to impaired oogenesis. An assay for disruption of oocyte maturation by chemical stressors has not been developed in Japanese medaka. Thus, using zebrafish (Danio rerio) as a model, objectives of the present study were to determine whether exposure to TBCO has effects on maturation of oocytes and to investigate potential mechanisms. Sexually mature female zebrafish were given a diet of 35.3 or 628.8 μg TBCO / g food for 14 days after which, stage IV oocytes were isolated to assess maturation in response to maturation inducing hormone. To explore potential molecular mechanisms, abundances of mRNAs of a suite of genes that regulate oocyte maturation were quantified by use of quantitative real-time PCR, and abundances of microRNAs were determined by use of miRNAseq. Ex vivo maturation of oocytes from fish exposed to TBCO was significantly less than maturation of oocytes from control fish. The percentage of oocytes which matured from control fish and those exposed to low and high TBCO were 89, 71, and 67%, respectively. Among the suite of genes known to regulate oocyte maturation, mRNA abundance of insulin like growth factor-3 was decreased by 1.64- and 3.44-fold in stage IV oocytes from females given the low and high concentrations of TBCO, respectively, compared to the control group. Abundances of microRNAs regulating the expression of proteins that regulate oocyte maturation, including processes related to insulin-like growth factor, were significantly different in stage IV oocytes from fish exposed to TBCO. Overall, results of this study indicated that impaired oocyte maturation might be a mechanism of reduced reproductive performance in TBCO-exposed fish. Results also suggested that effects of TBCO on oocyte maturation might be due to molecular perturbations on insulin-like growth factor signaling and expression of microRNAs.

溴化阻燃剂 1,2,5,6-四溴环辛烷 (TBCO) 已被证明会降低日本青鳉 ( Oryzias latipes ) 的繁殖力，转录组和蛋白质组分析间接证据表明，这种效应可能是由于卵子发生受损。日本青鳉中尚未开发出化学应激物对卵母细胞成熟破坏的测定方法。因此，本研究以斑马鱼（ Danio rerio ）为模型，确定暴露于 TBCO 是否对卵母细胞成熟有影响，并研究潜在机制。性成熟雌性斑马鱼的饮食为 35.3 或 628.8 μg TBCO/g 食物，持续 14 天，然后分离 IV 期卵母细胞，以评估对成熟诱导激素的反应。为了探索潜在的分子机制，通过使用定量实时 PCR 对调节卵母细胞成熟的一系列基因的 mRNA 丰度进行了定量，并通过使用 miRNAseq 确定了 microRNA 的丰度。暴露于 TBCO 的鱼的卵母细胞的离体成熟明显低于对照鱼的卵母细胞的成熟。对照鱼和暴露于低和高 TBCO 的鱼成熟的卵母细胞百分比分别为 89%、71% 和 67%。在已知调节卵母细胞成熟的一系列基因中，与对照组相比，给予低浓度和高浓度 TBCO 的雌性 IV 期卵母细胞中胰岛素样生长因子- 3 的 mRNA 丰度分别降低了 1.64 倍和 3.44 倍团体。 与暴露于 TBCO 的鱼相比，IV 期卵母细胞中调节卵母细胞成熟的蛋白质表达（包括与胰岛素样生长因子相关的过程）的 microRNA 丰度显着不同。总体而言，这项研究的结果表明，卵母细胞成熟受损可能是暴露于 TBCO 的鱼类繁殖性能下降的一个机制。结果还表明，TBCO 对卵母细胞成熟的影响可能是由于对胰岛素样生长因子信号传导和 microRNA 表达的分子扰动所致。