Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30668803
DOI
10.1093/toxsci/kfz023
PII: 5298326
Knihovny.cz E-resources
- Keywords
- Cx43 truncated isoforms, connexins, endocrine disruptors, gap junctional intercellular communication, polycyclic aromatic hydrocarbons, testicular cells,
- MeSH
- Cell Line MeSH
- Endocrine Disruptors chemistry toxicity MeSH
- Phosphorylation MeSH
- Connexin 43 genetics metabolism MeSH
- Leydig Cells drug effects metabolism pathology MeSH
- Gap Junctions drug effects metabolism pathology MeSH
- Cell Communication drug effects MeSH
- Mitogen-Activated Protein Kinases metabolism MeSH
- Mice MeSH
- Polycyclic Aromatic Hydrocarbons chemistry toxicity MeSH
- Sertoli Cells drug effects metabolism pathology MeSH
- Signal Transduction MeSH
- Cell Survival drug effects MeSH
- Bay-Region, Polycyclic Aromatic Hydrocarbon MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Endocrine Disruptors MeSH
- GJA1 protein, mouse MeSH Browser
- Connexin 43 MeSH
- Mitogen-Activated Protein Kinases MeSH
- Polycyclic Aromatic Hydrocarbons MeSH
Ambient air pollution and smoking are well-documented risk factors for male infertility. Prevalent air pollutants and cigarette smoke components, polycyclic aromatic hydrocarbons (PAHs), are environmental and occupational toxicants that act as chemicals disrupting endocrine regulation and reproductive potential in males. Testicular gap junctional intercellular communication (GJIC) is critical for normal development and function of testicular tissue, thus we assessed GJIC as a process potentially targeted by PAHs in testes. Lower MW PAHs with a bay or bay-like region rapidly dysregulated GJIC in Leydig TM3 cells by relocalization of major testicular gap junctional protein connexin 43 (Cx43) from plasma membrane to cytoplasm. This was associated with colocalization between Cx43 and ubiquitin in intracellular compartments, but without any effect on Cx43 degradation rate or steady-state Cx43 mRNA levels. A longer exposure to active PAHs decreased steady-state levels of full-length Cx43 protein and its 2 N-truncated isoforms. Inhibition of GJIC by PAHs, similarly to a prototypic GJIC-inhibitor TPA, was mediated via the MAP kinase-Erk1/2 and PKC pathways. Polycyclic aromatic hydrocarbon-induced GJIC dysregulation in testes was cell-type-specific because neither PAH dysregulated GJIC in Sertoli TM4 cells, despite PAHs were rapidly taken up by both Leydig TM3 as well as Sertoli TM4 cells. Because TPA effectively dysregulated GJIC in both testicular cell types, a unique regulator of GJIC targeted by PAHs might exist in Leydig TM3 cells. Our results indicate that PAHs could be a potential etiological agent contributing to reproductive dysfunctions in males through an impairment of testicular GJIC and junctional and/or nonjunctional functions of Cx43.
References provided by Crossref.org
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