AO168=O at environmentally relevant concentrations induces reproductive toxicity by causing germline apoptosis and cell cycle arrest in Caenorhabditiselegans.
Abstract — Entities Highlighted
Gene/ProteinChemicalDiseasePhenotypeAnatomyDev. Stage
Tris(2,4-di-tert-butylphenyl) phosphate (AO168=O) is an oxidized derivative of the widely used organophosphite antioxidant tris(2,4-di-tert-butylphenyl) phosphite (AO168). AO168=O, frequently detected in environments, represents a novel organophosphate ester, the toxicity of which is poorly known. We report the effects of exposure to AO168=O on reproductive characteristics of the nematode Caenorhabditis elegans. Exposure to 1 and 10 μg/L AO168=O decreases brood size, fertilized egg number, germ cell number, and length and area of gonad arms, and enhances germline apoptosis and expressions of genes ced-3, ced-4, ced-9, and egl-1 that regulate apoptosis; apoptosis was altered by RNAi of these apoptotic regulatory genes. Additionally, AO168=O (1 and 10 μg/L) reduced germ cell number in the meiotic zone of the gonad and decreased expressions of gld-2 and gld-3 and increased those of fbf-1, cye-1, and cdk-2, suggesting that cell-cycle arrest was induced. This cell-cycle arrest could be altered by RNAi of these five genes; expression of gld-2 and gld-3 was increased by fbf-1, cye-1, and cdk-2 RNAi. AO168=O (10 μg/L) also decreased expressions of germline rho-1, let-502, and cyk-4 required for maintenance of the gonadal sheath, leading to formation of an abnormal gonadal sheath. After exposure to concentrations of 1 and 10 μg/L, AO168=O also accumulated in the nematode body. Therefore, we demonstrate that exposure to AO168=O at environmentally relevant concentrations can induce reproductive damage in a species.
Relation Network
Specialists Used
deepseek: 35gene_gene: 8gene_expression: 4
All Extracted Relations (50)
| Entity 1 | Relation | Entity 2 | Confidence | Specialist | Direction |
|---|---|---|---|---|---|
| cye-1 | regulation | cdk-2 | 100% | gene_gene | supports |
| gld-3 | regulation | cye-1 | 100% | gene_gene | supports |
| gld-2 | regulation | cdk-2 | 100% | gene_gene | supports |
| gld-2 | expressed in | cell | 100% | gene_expression | supports |
| ced-3 | regulation | ced-9 | 100% | gene_gene | supports |
| ced-3 | regulation | egl-1 | 100% | gene_gene | supports |
| let-502 | regulation | cyk-4 | 100% | gene_gene | supports |
| gld-2 | regulation | gld-3 | 98% | gene_gene | supports |
| gonad | expressed in | ced-4 | 94% | gene_expression | supports |
| gonad | expressed in | gld-3 | 90% | gene_expression | supports |
| AO168=O | positively regulates | egl-1 | 85% | deepseek | supports |
| ced-3 | regulates | apoptosis | 85% | deepseek | supports |
| ced-4 | regulates | apoptosis | 85% | deepseek | supports |
| ced-9 | regulates | apoptosis | 85% | deepseek | supports |
| egl-1 | regulates | apoptosis | 85% | deepseek | supports |
| AO168=O | negatively regulates | germ cell number in the meiotic zone | 85% | deepseek | refutes |
| AO168=O | negatively regulates | gld-2 | 85% | deepseek | refutes |
| AO168=O | negatively regulates | gld-3 | 85% | deepseek | refutes |
| AO168=O | positively regulates | fbf-1 | 85% | deepseek | supports |
| AO168=O | positively regulates | cye-1 | 85% | deepseek | supports |
| AO168=O | positively regulates | cdk-2 | 85% | deepseek | supports |
| AO168=O | causes phenotype | cell-cycle arrest | 85% | deepseek | supports |
| gld-2 | negatively regulates | cell-cycle arrest | 85% | deepseek | refutes |
| gld-3 | negatively regulates | cell-cycle arrest | 85% | deepseek | refutes |
| fbf-1 | positively regulates | cell-cycle arrest | 85% | deepseek | supports |
| cye-1 | positively regulates | cell-cycle arrest | 85% | deepseek | supports |
| cdk-2 | positively regulates | cell-cycle arrest | 85% | deepseek | supports |
| AO168=O | negatively regulates | rho-1 | 85% | deepseek | refutes |
| AO168=O | negatively regulates | let-502 | 85% | deepseek | refutes |
| AO168=O | negatively regulates | cyk-4 | 85% | deepseek | refutes |
| rho-1 | positively regulates | maintenance of the gonadal sheath | 85% | deepseek | supports |
| let-502 | positively regulates | maintenance of the gonadal sheath | 85% | deepseek | supports |
| cyk-4 | positively regulates | maintenance of the gonadal sheath | 85% | deepseek | supports |
| AO168=O | causes phenotype | abnormal gonadal sheath | 85% | deepseek | supports |
| AO168=O | expressed in | nematode body | 85% | deepseek | supports |
| AO168=O | causes phenotype | reproductive damage | 85% | deepseek | supports |
| AO168=O | negatively regulates | brood size | 85% | deepseek | refutes |
| AO168=O | negatively regulates | fertilized egg number | 85% | deepseek | refutes |
| AO168=O | negatively regulates | germ cell number | 85% | deepseek | refutes |
| AO168=O | negatively regulates | length of gonad arms | 85% | deepseek | refutes |
| AO168=O | negatively regulates | area of gonad arms | 85% | deepseek | refutes |
| AO168=O | positively regulates | germline apoptosis | 85% | deepseek | supports |
| AO168=O | positively regulates | ced-3 | 85% | deepseek | supports |
| AO168=O | positively regulates | ced-4 | 85% | deepseek | supports |
| AO168=O | positively regulates | ced-9 | 85% | deepseek | supports |
| gonad | expressed in | ced-3 | 83% | gene_expression | supports |
| fbf-1 | regulation | cdk-2 | 68% | gene_gene | supports |
| ced-3 | regulates | ced-4 | 59% | — | supports |
| let-502 | required for | cyk-4 | 59% | — | supports |
| gld-2 | positively regulates | gld-3 | 59% | — | uncertain |