J 2019

Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins

KUBINCOVÁ, Petra, Eliška SYCHROVÁ, Jan RAŠKA, Amrita BASU, Affiefa YAWER et. al.

Basic information

Original name

Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins

Authors

KUBINCOVÁ, Petra (203 Czech Republic, belonging to the institution), Eliška SYCHROVÁ (203 Czech Republic, belonging to the institution), Jan RAŠKA (203 Czech Republic, belonging to the institution), Amrita BASU (356 India, belonging to the institution), Affiefa YAWER (586 Pakistan, belonging to the institution), Aneta DYDOWICZOVÁ (203 Czech Republic, belonging to the institution), Pavel BABICA (203 Czech Republic, belonging to the institution) and Iva SOVADINOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Toxicological sciences, OXFORD, Academic Press, 2019, 1096-6080

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30108 Toxicology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.703

RIV identification code

RIV/00216224:14310/19:00108198

Organization unit

Faculty of Science

DOI

UT WoS

000475894000009

Keywords in English

connexins; Cx43 truncated isoforms; endocrine disruptors; gap junctional intercellular communication; polycyclic aromatic hydrocarbons; testicular cells

Tags

Tags

International impact, Reviewed
Změněno: 3/4/2020 12:45, Mgr. Marie Šípková, DiS.

Abstract

V originále

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.

Links

EF16_013/0001761, research and development project
Name: RECETOX RI
GJ16-10775Y, research and development project
Name: Mezibuněčná komunikace zprostředkovaná mezerovými spoji jako cíl endokrinních disruptorů v testikulárních buňkách
Investor: Czech Science Foundation
LM2015051, research and development project
Name: Centrum pro výzkum toxických látek v prostředí (Acronym: RECETOX RI)
Investor: Ministry of Education, Youth and Sports of the CR