Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive functi...Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive function of offspring are not yet fully understood.The present study classified institute of cancer research(ICR)mice into control and BDE-209 treatment groups,administering doses of 0 and 75 mg/(kg·day),respectively.After 50 days of exposure,normal female mice were co-housed with the male mice,and their male offspring were sacrificed at 2 and 12 months of age.Paternal BDE-209 exposure reduced both sperm quantity and quality in offspring.Furthermore,exposure to BDE-209 resulted in DNA damage and the upregulation of the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)DNA-sensing and inflammatory signaling pathways.The activation resulted in Z-DNA binding protein 1(ZBP1)binding to the mitochondrial antiviral signaling protein(MAVS),subsequently activating mitochondrial apoptosis in the testes.The activation of the cGAS-STING pathway inhibited mitophagy,leading to senescence in the testes of male offspring.In vitro studies indicated that the cGAS inhibitor RU320521(RU.521)effectively reversed the cGAS-STING pathway activation,alleviated the mitophagy inhibition,and decreased apoptosis and senescence in mouse spermatocyte line GC-2spd cells treated with BDE-209.The results showed that paternal BDE-209 exposure might disrupt spermatogenesis in mouse offspring by activating the cGAS-STING pathway and inhibiting mitophagy.This study provides essential data on the toxicity of BDE-209 to male reproduction and have important scientific and practical implications for maintaining biodiversity and population health in general.展开更多
基金supported by the National Natural Science Foundation of China(No.32171492)。
文摘Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive function of offspring are not yet fully understood.The present study classified institute of cancer research(ICR)mice into control and BDE-209 treatment groups,administering doses of 0 and 75 mg/(kg·day),respectively.After 50 days of exposure,normal female mice were co-housed with the male mice,and their male offspring were sacrificed at 2 and 12 months of age.Paternal BDE-209 exposure reduced both sperm quantity and quality in offspring.Furthermore,exposure to BDE-209 resulted in DNA damage and the upregulation of the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)DNA-sensing and inflammatory signaling pathways.The activation resulted in Z-DNA binding protein 1(ZBP1)binding to the mitochondrial antiviral signaling protein(MAVS),subsequently activating mitochondrial apoptosis in the testes.The activation of the cGAS-STING pathway inhibited mitophagy,leading to senescence in the testes of male offspring.In vitro studies indicated that the cGAS inhibitor RU320521(RU.521)effectively reversed the cGAS-STING pathway activation,alleviated the mitophagy inhibition,and decreased apoptosis and senescence in mouse spermatocyte line GC-2spd cells treated with BDE-209.The results showed that paternal BDE-209 exposure might disrupt spermatogenesis in mouse offspring by activating the cGAS-STING pathway and inhibiting mitophagy.This study provides essential data on the toxicity of BDE-209 to male reproduction and have important scientific and practical implications for maintaining biodiversity and population health in general.
