A transcriptomics-based analysis provides insights into the sex-dependent reproductive toxicity of DEHP in zebrafish (Danio rerio).

Di-(2-ethylhexyl) phthalate (DEHP) threatens human and wildlife health seriously, yet sex-dependent reproductive toxicity remains unclear. Therefore, in this study, we exposed zebrafish to various concentrations (0.01, 0.1, 1.0, and 2.0 mg/L) of DEHP for 28 days. Results indicate that DEHP exposure induced oxidative stress as a common response in both sexes and more pronounced reproductive toxicity to males than females. In males, sperm development stagnated at spermatogonia and enriched pathways were mainly associated with ribosome (Rps3, Rps27a) and endoplasmic reticulum stress(Hspa5). In females, oocyte development was affected at later stages and the pathways were mainly lipid metabolism and GnRH signaling pathway. Hub genes from PPI in females were Cacna2d3, Prkcba, Calm2a, Pla2g4aa in SCvsHigh while Pla2g4aa in SCvsLow. Overall, these findings provide new insights into the molecular mechanisms of DEHP toxicity, which is crucial for understanding its impact on reproductive health and ecological risk assessment.