Association between gestational and lactational DCBQ exposure and developmental toxicity in female offspring: Potential role of gut microbiota dysbiosis

2,6-dichloro-1,4-benzoquinone (DCBQ), a novel Disinfection by-product (DBPs), can enter the gut through various pathways and perturb the gut microbiota, which plays a critical role in offspring development. This study established a rat model of gestational and lactational DCBQ exposure to investigate developmental toxicity of DCBQ through gut microbiota and metabolomics. The results showed that DCBQ induced gut dysbiosis in both maternal and offspring rats, accompanied by significant metabolic disturbances. The affected pathways included prolactin signaling, steroid hormone biosynthesis, and ovarian steroidogenesis. Further analyses revealed ovarian and uterus dysfunction in female offspring, characterized by hormonal imbalances, including decreased serum estradiol (E2) levels and elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, along with the reduced mRNA expression levels of key genes in regulating hormones like estrogen receptor 2 (esr2), cytochrome P450 family 17 subfamily A polypeptide 1 (cyp17a1), and cytochrome P450 family 19 subfamily A polypeptide 1 (cyp19a1). Notably, altered gut microbiota composition strongly correlated with changes in metabolites, hormones, and gene expression levels. Based on these findings, we speculate that DCBQ may have endocrine-disrupting effects. This study found that DCBQ affected the development of female offspring rats, providing new insights into the developmental toxicity of DCBQ, especially the potential mechanism of affecting the development of female offspring, and contributing to a comprehensive understanding of the health hazards associated with DCBQ exposure.