Lifetime co-exposure of parental zebrafish to benzophenone-3 and titanium dioxide nanoparticles leads to developmental neurotoxicity and thyroid endocrine disruption in their offspring

Benzophenone-3 (BP3) is a prevalent environmental UV filter widely used in personal care products, and titanium dioxide nanoparticles (nano-TiO₂), another commonly applied material in consumer goods and industrial applications, may coexist with BP3 in environmental media. This study investigates the potential parental transfer of BP3 and transgenerational effects on development and thyroid hormone homeostasis in F1 larvae following lifetime parental exposure to BP3 and nano-TiO₂. Zebrafish embryos were exposed to environmentally relevant concentrations of BP3 (10 μg/L), nano-TiO₂ (100 μg/L), and their combination from 6 hours post-fertilization (hpf) to 150 days. Results showed the presence of BP3 in the gonads of F0 and F1 embryos, with combined exposure alleviating BP3 accumulation. Parental BP3 exposure increased BP3 levels in F1 embryos, causing various developmental neurotoxic effects including decreased survival rates, somite counts, hatching rates, midbrain-hindbrain junction abnormalities, and heightened locomotor responses in F1 offspring. These effects were accompanied by their reduced axonal growth, impaired neurogenesis, and altered neurotransmitters levels. Additionally, decrease thyroxin (T4) levels were observed in F1 eggs, consistent with F0 adults' plasma levels, indicating maternal transmission of thyroid endocrine disruption to the offspring. Furthermore, significant changes in the expression of genes related to hypothalamic-pituitary-thyroid (HPT) axis were observed across two generations, potentially contributing to transgenerational thyroid hormone disruption. Taken together, our study illustrated that parental exposure to BP3 and nano-TiO₂ can induce developmental neurotoxicity and thyroid endocrine disruption in offspring, emphasizing the importance of conducting transgenerational toxicity tests for assessing the environmental risks associated with co-exposure to UV filters and nanoparticles.