Endocrine-disrupting chemicals rapidly affect intercellular signaling in Leydig cells
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32739526
DOI
10.1016/j.taap.2020.115177
PII: S0041-008X(20)30303-3
Knihovny.cz E-resources
- Keywords
- Connexins, Endocrine-disrupting chemicals, Gap junctional intercellular communication, Leydig cells, Reproductive toxicants, Steroidogenesis,
- MeSH
- Endocrine Disruptors toxicity MeSH
- Phenols toxicity MeSH
- Connexin 43 genetics metabolism MeSH
- Leydig Cells drug effects MeSH
- Cell Communication drug effects MeSH
- Mice MeSH
- Signal Transduction drug effects MeSH
- Cell Survival drug effects MeSH
- Dose-Response Relationship, Drug 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
- Phenols MeSH
- GJA1 protein, mouse MeSH Browser
- Connexin 43 MeSH
- nonylphenol MeSH Browser
A decline in male fertility possibly caused by environmental contaminants, namely endocrine-disrupting chemicals (EDCs), is a topic of public concern and scientific interest. This study addresses a specific role of testicular gap junctional intercellular communication (GJIC) between adjacent prepubertal Leydig cells in endocrine disruption and male reproductive toxicity. Organochlorine pesticides (lindane, methoxychlor, DDT), industrial chemicals (PCB153, bisphenol A, nonylphenol and octylphenol) as well as personal care product components (triclosan, triclocarban) rapidly dysregulated GJIC in murine Leydig TM3 cells. The selected GJIC-inhibiting EDCs (methoxychlor, triclosan, triclocarban, lindane, DDT) caused the immediate GJIC disruption by the relocation of gap junctional protein connexin 43 (Cx43) from the plasma membrane and the alternation of Cx43 phosphorylation pattern (Ser368, Ser279, Ser282) of its full-length and two N-truncated isoforms. After more prolonged exposure (24 h), EDCs decreased steady-state levels of full-length Cx43 protein and its two N-truncated isoforms, and eventually (triclosan, triclocarban) also tight junction protein Tjp-1. The disturbance of GJIC was accompanied by altered activity of mitogen-activated protein kinases MAPK-Erk1/2 and MAPK-p38, and a decrease in stimulated progesterone production. Our results indicate that EDCs might disrupt testicular homeostasis and development via disruption of testicular GJIC, a dysregulation of junctional and non-junctional functions of Cx43, activation of MAPKs, and disruption of an early stage of steroidogenesis in prepubertal Leydig cells. These critical disturbances of Leydig cell development and functions during a prepubertal period might be contributing to impaired male reproduction health later on.
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References provided by Crossref.org
Toxicity of bisphenol A and its replacements in the mice Leydig cells in vitro
Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing
