Triphenyl phosphate induced reproductive toxicity through the JNK signaling pathway in Caenorhabditis elegans

Triphenyl phosphate (TPHP) is a widely used aryl organophosphate flame retardant (OPFR) that has attracted attention due to its frequent detection in the environment and living organisms. To date, the reproductive toxicity of TPHP has been investigated in organisms, but its molecular mechanisms are not fully understood. Caenorhabditis elegans (C. elegans) is the ideal animal for the study of reproductive toxicity following environ-mental pollutants, with short generation times, intact reproductive structures, and hermaphroditic fertilization. This study aimed to explore the reproductive dysfunction and molecular mechanisms induced by TPHP exposure in C. elegans. Specifically, exposure to TPHP resulted in a reduction in the number of eggs laid and developing embryos in utero, an increase in the number of apoptotic gonadal cells, and germ cell cycle arrest. The JNK signaling pathway is a potential pathway inducing reproductive toxicity following TPHP exposure based on transcriptome sequencing (RNA-seq). Moreover, TPHP exposure induced down-regulation of vhp-1 and kgb-2 gene transcription levels, and the knockout of vhp-1 and kgb-2 in the mutant strains exhibited more severe toxicity in apoptotic gonad cells, embryos, and eggs developing in utero, suggesting that vhp-1 and kgb-2 genes play a crucial role in TPHP-induced reproductive toxicity. Our data provide convergent evidence showing that TPHP exposure results in reproductive dysfunction through the JNK signaling pathway and improve our un-derstanding of the ecotoxicity and toxicological mechanisms of aryl-OPFRs.

Automated summary

This study explored the reproductive dysfunction and molecular mechanisms induced by Triphenyl phosphate (TPHP) exposure in Caenorhabditis elegans. The results showed that TPHP exposure reduced the number of eggs laid, increased apoptotic gonadal cells, and arrested the germ cell cycle. Transcriptome sequencing revealed the JNK signaling pathway as a potential pathway for reproductive toxicity. Knockout experiments confirmed the crucial role of vhp-1 and kgb-2 genes in TPHP-induced reproductive toxicity.