Endocrine Disruption throughout the Hypothalamus–Pituitary–Gonadal–Liver (HPGL) Axis in Marine Medaka (Oryzias melastigma) Chronically Exposed to the Antifouling and Chemopreventive Agent, 3,3′-Diindolylmethane (DIM)
| Autor: | Lianguo Chen, Chenyan Hu, Paul K.S. Lam, Drew R. Peterson, Doris W.T. Au, Rui Ye, Bingsheng Zhou, Pei-Yuan Qian, Weipeng Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty 3 3'-Diindolylmethane Indoles Biofouling Oryzias Hypothalamus Diindolylmethane Ovary Endocrine Disruptors 010501 environmental sciences Toxicology 01 natural sciences Vitellogenins 03 medical and health sciences Vitellogenin chemistry.chemical_compound Internal medicine medicine Animals Endocrine system Protein Precursors Gonads Testosterone 0105 earth and related environmental sciences biology Egg Proteins General Medicine biology.organism_classification 030104 developmental biology medicine.anatomical_structure Endocrinology Liver chemistry Pituitary Gland biology.protein Female Hormone |
| Zdroj: | Chemical Research in Toxicology. 29:1020-1028 |
| ISSN: | 1520-5010 0893-228X |
| Popis: | Despite being proposed as a promising antifouling and chemopreventive agent, the environmental risks of 3,3'-diindolylmethane (DIM) are scarcely investigated. Therefore, this study used adult marine medaka (Oryzias melastigma) as a model organism to examine the toxicological effects and underlying mechanism of DIM throughout the hypothalamus-pituitary-gonadal-liver (HPGL) axis following 28 days of exposure to low DIM concentrations (0 and 8.46 μg/L). The results showed that altered gene transcription in the hypothalamus, pituitary, and gonads contributed to the great imbalance in hormone homeostasis. The lowered estradiol (E2)/testosterone (T) and E2/11-keto-testosterone (11-KT) ratios in female plasma resulted in decreased synthesis and levels of vitellogenin (VTG) and choriogenin in the liver and plasma, and vice versa in males. Subsequently, VTG and choriogenin deficiency blocked the reproductive function of the ovary as indicated by decreased fecundity and offspring viability, whereas in male medaka, DIM mainly targeted the liver and induced severe vacuolization. Proteomic profiling of plasma revealed that the sex-specific susceptibility to DIM could be attributed to the increased detoxification and oxidative defense in males. Overall, this study identified the endocrine disruption and reproductive impairment potency of DIM and first elucidated its mechanisms of action in medaka. The differential responses to DIM (estrogenic activities in the male but antiestrogenic activities in the female) provided sensitive biomarkers characteristic of each sex. Considering the chemical stability and potent endocrine disturbance at low concentration, the application of DIM either as an antifouling or chemopreventive agent should be approached with caution in marine environments. |
| Databáze: | OpenAIRE |
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