Dibutyl phthalate (DBP) and diisobutyl phthalate (DiBP) have been reported to exhibit reproductive toxicity in vertebrates. However, the combined effect of DBP and DiBP on offspring of exposed parents remains unclear, especially for aquatic organisms such as fish. The aims of this study were to assess the effects of parental co-exposure to DBP and DiBP on early development of zebrafish offspring, and to explore the potential molecular mechanisms involved. The early developmental indicators and transcriptomic profiles of F1 larvae were examined after parental exposure to DBP, DiBP and their mixtures (Mix) for 30 days. Results showed that parental exposure to DBP and DiBP, alone or in combination, resulted in increased hatchability at 48 hpf and heart rate at 96 hpf, and increased the prevalence of malformations and mortality in F1 larvae. Generalized linear model (GLM) suggested an antagonistic interactive effect between DBP and DiBP on mortality and malformations of F1 larvae. The transcriptomic analysis revealed that the molecular mechanisms of parental co-exposure were different from those of either chemical alone. Disruption of molecular functions involved unfolded protein binding, E-box binding and photoreceptor activity in F1 larvae. These findings provide initial insights in the potential mechanism of action of parental co-exposure to DBP and DiBP.

据报道邻苯二甲酸二丁酯（DBP）和邻苯二甲酸二异丁酯（DiBP）在脊椎动物中表现出生殖毒性。但是，DBP和DiBP对暴露父母的后代的综合作用仍不清楚，尤其是对于鱼类等水生生物。这项研究的目的是评估父母共同暴露于DBP和DiBP对斑马鱼后代早期发育的影响，并探讨涉及的潜在分子机制。父母暴露于DBP，DiBP及其混合物（Mix）30天后，检查了F1幼虫的早期发育指标和转录组谱。结果表明，父母单独或联合使用DBP和DiBP会导致48 hpf的孵化率增加和96 hpf的心率增加，并增加F1幼虫畸形的发生率和死亡率。广义线性模型（GLM）提示DBP和DiBP之间对F1幼虫的死亡率和畸形具有拮抗作用。转录组分析表明，父母共同暴露的分子机制不同于任何一种单独的化学物质。分子功能的破坏涉及F1幼虫中未结合的蛋白质结合，E-box结合和感光细胞活性。这些发现为父母共同暴露于DBP和DiBP的潜在作用机理提供了初步见识。分子功能的破坏涉及F1幼虫中未结合的蛋白质结合，E-box结合和感光细胞活性。这些发现为父母共同暴露于DBP和DiBP的潜在作用机理提供了初步见识。分子功能的破坏涉及F1幼虫中未结合的蛋白质结合，E-box结合和感光细胞活性。这些发现为父母共同暴露于DBP和DiBP的潜在作用机理提供了初步见识。