Endocrine-disrupting chemicals rapidly affect intercellular signaling in Leydig cells
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
32739526
DOI
10.1016/j.taap.2020.115177
PII: S0041-008X(20)30303-3
Knihovny.cz E-zdroje
- Klíčová slova
- Connexins, Endocrine-disrupting chemicals, Gap junctional intercellular communication, Leydig cells, Reproductive toxicants, Steroidogenesis,
- MeSH
- endokrinní disruptory toxicita MeSH
- fenoly toxicita MeSH
- konexin 43 genetika metabolismus MeSH
- Leydigovy buňky účinky léků MeSH
- mezibuněčná komunikace účinky léků MeSH
- myši MeSH
- signální transdukce účinky léků MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- endokrinní disruptory MeSH
- fenoly MeSH
- GJA1 protein, mouse MeSH Prohlížeč
- konexin 43 MeSH
- nonylphenol MeSH Prohlížeč
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.
RECETOX Faculty of Science Masaryk University Kamenice 753 5 building A29 625 00 Brno Czech Republic
Citace poskytuje Crossref.org
Toxicity of bisphenol A and its replacements in the mice Leydig cells in vitro
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