毒理基因组学
邻苯二甲酸二丁酯
邻苯二甲酸盐
毒性
苏木精
生物信息学
男科
生物
氧化应激
化学
毒理
染色
生物化学
基因表达
医学
遗传学
基因
有机化学
作者
Katarina Baralić,Dragica Jorgovanović,Katarina Živančević,Aleksandra Buha Djordjevic,Evica Antonijević Miljaković,Milica Miljković,Jelena Kotur-Stevuljević,Biljana Antonijević,Danijela Đukić-Ćosić
出处
期刊:Chemosphere
[Elsevier]
日期:2021-03-01
卷期号:267: 129296-129296
被引量:18
标识
DOI:10.1016/j.chemosphere.2020.129296
摘要
The aim of this study was to: (i) determine and compare the capacity of bis (2 –ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), bisphenol A (BPA), and their mixture to produce testicular toxicity after the subacute exposure; (ii) explore the mechanisms behind the observed changes using in silico toxicogenomic approach. Male rats were randomly split into groups (n = 6): (1) Control (corn oil); (2) DEHP (50 mg/kg b.w./day); (3) DBP (50 mg/kg b.w./day); (4) BPA (25 mg/kg b.w./day); and (5) MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA). Animals were sacrificed after 28 days of oral exposure, testes were extracted and prepared for histological assessments under the light microscope (haematoxylin and eosin staining) and redox status analysis. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite (https://toppgene.cchmc.org) were used for data-mining. Present pathohistological study has demonstrated more pronounced testicular toxicity of the MIX group (desquamated germinal epithelium cells, enlarged cells with hyperchromatic nuclei, multinucleated cell forms and intracytoplasmic vacuoles) in comparison with the single substances, while effects on redox status parameters were either more prominent, or present only in the MIX group. In silico investigation revealed 20 genes linked to male reproductive disorders, affected by all three investigated substances. Effects on metabolism, AhR pathway, apoptosis and oxidative stress could be singled out as the most probable mechanisms involved in the subacute DEHP, DBP and BPA mixture testicular toxicity, while the effect on oxidative stress parameters was confirmed by in vivo experiment.
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