Tetrabromobisphenol A-bis(2,3-dibromopropyl ether)(TBBPA-BDBPE),a widely used flame retardant,has been frequently detected in various environmental compartments,but its health hazard remains largely unknown.Here,we in...Tetrabromobisphenol A-bis(2,3-dibromopropyl ether)(TBBPA-BDBPE),a widely used flame retardant,has been frequently detected in various environmental compartments,but its health hazard remains largely unknown.Here,we investigated the adverse effects of TBBPA-BDBPE(50 and 1000μg/kg/day)on postnatal testis development in CD-1 mice and the underlying mechanism.Following the first week of maternal exposure,neonatal mice in the high-dose group exhibited reduced seminiferous tubule area,fewer Sertoli cells and germ cells,and damaged microtubules in Sertoli cells;even microtubule damage was also observed in the low-dose group.When exposure extended to adulthood,male offspring in the high-dose group presented more remarkable alterations in reproductive parameters,including reduced sperm count;in the low-dose group,microtubule damage was also observable,along with blood−testis barrier impairment.Further molecular docking analysis and tubulin polymerization assay indicated that TBBPA-BDBPE could interact with tubulin and disrupt its polymerization.Moreover,we observed attenuated microtubules in mouse Sertoli cells in vitro(TM4)following TBBPABDBPE treatment,suggesting that TBBPA-BDBPE impaired testis development possibly by interfering with tubulin dynamics.This study not only highlights the male reproductive hazard of TBBPA-BDBPE but also greatly improved the understanding of the molecular mechanism for male reproductive toxicity of chemicals.展开更多
基金supported by the National Key Research and Development Program of China(2018YFA0901103)the National Natural Science Foundation of China(21876196).
文摘Tetrabromobisphenol A-bis(2,3-dibromopropyl ether)(TBBPA-BDBPE),a widely used flame retardant,has been frequently detected in various environmental compartments,but its health hazard remains largely unknown.Here,we investigated the adverse effects of TBBPA-BDBPE(50 and 1000μg/kg/day)on postnatal testis development in CD-1 mice and the underlying mechanism.Following the first week of maternal exposure,neonatal mice in the high-dose group exhibited reduced seminiferous tubule area,fewer Sertoli cells and germ cells,and damaged microtubules in Sertoli cells;even microtubule damage was also observed in the low-dose group.When exposure extended to adulthood,male offspring in the high-dose group presented more remarkable alterations in reproductive parameters,including reduced sperm count;in the low-dose group,microtubule damage was also observable,along with blood−testis barrier impairment.Further molecular docking analysis and tubulin polymerization assay indicated that TBBPA-BDBPE could interact with tubulin and disrupt its polymerization.Moreover,we observed attenuated microtubules in mouse Sertoli cells in vitro(TM4)following TBBPABDBPE treatment,suggesting that TBBPA-BDBPE impaired testis development possibly by interfering with tubulin dynamics.This study not only highlights the male reproductive hazard of TBBPA-BDBPE but also greatly improved the understanding of the molecular mechanism for male reproductive toxicity of chemicals.
