Tetrachlorobisphenol A mediates reproductive toxicity in Caenorhabditis elegans via DNA damage-induced apoptosis

Tetrachlorobisphenol A (TCBPA), an alternative to tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and could potentially impact the reproductive system of organisms. However, the mechanisms underlying TCBPA-mediated reproductive effects remain unclear. Herein, we exposed Caenorhabditis elegans (C. elegans, L4 larvae) to TCBPA at environmentally relevant doses (0-100 μg/L) for 24 h. Exposure to TCBPA at concentrations of 1-100 μg/L impaired fertility of C. elegans, as indicated by brood size. After staining, the number of germline cells decreased in a dose-dependent manner, whereas germline cell corpses increased in exposed nematodes (10-100 μg/L TCBPA). Moreover, the expression of genes related to the germline apoptosis pathway was regulated following exposure to 100 μg/L TCBPA, indicating the potential role of DNA damage in TCBPA-induced apoptosis. Apoptosis was nearly abolished in ced-4 and ced-3 mutants and blocked in hus-1, egl-1, cep-1, and ced-9 mutants. Numerous foci were detected in TCBPA (100 μg/L)-exposed hus-1::GFP strains. These results indicate that TCBPA induces hus-1-mediated DNA damage and further causes apoptosis via a cep-1-dependent pathway. Our data provide evidence that TCBPA causes reproductive toxicity via DNA damage-induced apoptosis.