Tetrachlorobisphenol a Induced Reproductive Toxicity in Caenorhabditis Elegans Involves DNA Damage-Induced Apoptosis

Abstract

Tetrachlorobisphenol A (TCBPA), an alternative to tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and organisms and poses potential reproductive effects. However, the mechanisms of TCBPA on reproduction remain largely unclear. In this study, Caenorhabditis elegans (C. elegans, L4 larvae) was exposed to TCBPA at environmentally relevant doses (0–100 μg/L) for 24 h. Exposure to TCBPA impaired fertility as indicated by brood size. After staining, the number of germline cells decreased in a dose-dependent manner, whereas that of germline cell corpses increased in exposed nematodes (10–100 μg/L TCBPA). Moreover, the expression of genes related to germline apoptosis pathway was regulated by exposure to 100 μg/L TCBPA, and ced-3, ced-9, cep-1, and egl-1 played critical roles, indicating that DNA damage is involved 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. More foci was detected in hus-1::GFP strains exposed to 100 μg/L TCBPA. These results indicated that TCBPA induces DNA damage, mediated by hus-1, and further causes apoptosis through cep-1-dependent pathway. Our data provide evidence that TCBPA causes reproductive toxicity via DNA damage-induced apoptosis.

Keywords: Tetrachlorobisphenol A, Reproductive toxicity, Germline apoptosis, DNA damage, Caenorhabditis elegans