Transgenerational effects of maternal exposure to diethyl phthalate (DEP) and dimethyl sulfoxide (DMSO) in zebrafish...

The diethyl phthalate (DEP) is a known disruptor of craniofacial chondrogenesis, and dimethyl sulfoxide (DMSO) is widely used as a co-solvent. However, whether there is an interaction between DMSO and DEP in the toxicological experiments warrants further investigation. The present study investigated the transgenerational effects on females (F0) exposed to aerated water (blank), DMSO (control), and DEP dissolved in DMSO (treatment) and employed RNA-Seq to analyze transcriptional changes in the F0 ovaries and in 24-hour post-fertilization (hpf) embryos from the F1 and F2 generations. In the ovary, compared between the control and treatment group, Cyp19a1a mRNA expression was upregulated by DMSO exposure and decreased through DEP exposure, which may be related to alterations in the methylation levels of the Cyp19a1a promoter. Either DEP or DMSO induced abnormal craniofacial cartilage development in the early larvae of the F2 generation. During oocyte maturation, DEP exposure markedly disrupted follicle activation and vitellogenin steps. Gene Ontology (GO) enrichment and the number of differentially expressed genes (DEGs) revealed that the F2 had higher influence levels than the F1. The influence on larval biological processes reveals that the DEP might modulate rather than exacerbate DMSO-induced changes. These findings suggest that DEP has transgenerational effects on aquatic vertebrates, while also highlighting that the influences of DMSO should not be overlooked in experimental designs.