New insights into the reproductive endocrine disruption of early-life dimethyl phthalate exposure in female zebrafish (Danio rerio).

Dimethyl phthalate (DMP) is a ubiquitous environmental contaminant due to its persistence and inefficient removal during wastewater treatment. However, the long-term consequences of early-life DMP exposure for female reproductive health remain insufficiently understood. In this investigation, zebrafish embryos were subjected to environmentally relevant concentrations (10, 100, 1000 μg/L) of DMP from 2 h post-fertilization (hpf) to 28 days post-fertilization (dpf), and maintained in clean water until adulthood (150 dpf). The results showed that early-life DMP exposure significantly impaired oocyte maturation and fecundity in adult females. Offspring derived from DMP-exposed females mated with unexposed males exhibited reduced survival and increased malformation rates. DMP exposure also induced endocrine disruption, altering hormone levels at 45 dpf (E2 and T) and in adults (E2, T, FSH, LH, and AMH). This was associated with dysregulated expression of key genes (gnrh2, gnrh3, fshβ, lhβ, cyp11a1, and cyp19a) along the HPGL axis. Additionally, molecular docking analysis further demonstrated relatively strong binding of DMP to the aromatase isoforms CYP19A and CYP19B, suggesting interference with estrogen-androgen conversion. Transcriptomic analysis of ovarian tissue identified significant disruption of pathways related to extracellular matrix-receptor interaction, focal adhesion, and steroid hormone biosynthesis. These findings reveal the mechanisms through which early-life DMP exposure causes lasting reproductive toxicity in adult female zebrafish, highlighting its potential ecological and health risks.