Serum Metabolomic Alterations and Developmental Toxicity Induced by Diquat Exposure in Pregnant Rats and Their...

The reproductive and developmental toxicity of diquat (DQ), a widely used herbicide, during pregnancy remains insufficiently characterized. This study investigated the effects of repeated DQ exposure on fetal development and maternal metabolism in pregnant Sprague-Dawley rats. The rats were administered sublethal doses of DQ (28.88 and 57.57 mg/kg), and maternal serum sex hormones, fetal skeletal development, and serum metabolomic profiles were evaluated. Compared with controls, serum estradiol levels were significantly decreased in the high-dose exposure group, whereas luteinizing hormone and follicle-stimulating hormone levels remained unchanged. Significant alterations in malondialdehyde, superoxide dismutase, and glutathione levels indicated oxidative stress in exposed rats. Severe fetal skeletal ossification deficits and developmental delays were observed, with incomplete or failed ossification of the occipital bone, sternum, caudal vertebrae, and pelvis, with litter-level incidences reaching 100%. Metabolomic analysis identified distinct serum metabolic profiles between DQ-exposed and control groups, suggesting ovarian steroidogenesis, phenylalanine metabolism, and aldosterone synthesis and secretion as key pathways affected by DQ toxicity. These findings suggest that repeated maternal exposure to DQ induces oxidative stress, disrupts metabolic and hormonal homeostasis, and causes delayed fetal skeletal development. This study provides novel evidence for understanding the reproductive and developmental toxicity of DQ and its potential metabolic mechanisms.