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@article{1708556,
author = {Yawer, Affiefa and Sychrová, Eliška and Labohá, Petra and Raška, Jan and Jambor, Tomas and Babica, Pavel and Sovadinová, Iva},
article_location = {SAN DIEGO},
article_number = {October 2020},
doi = {http://dx.doi.org/10.1016/j.taap.2020.115177},
keywords = {Connexins; Endocrine-disrupting chemicals; Gap junctional intercellular communication; Leydig cells; Reproductive toxicants; Steroidogenesis},
language = {eng},
issn = {0041-008X},
journal = {Toxicology and applied pharmacology},
note = {CZ.02.1.01/0.0/0.0/18_046/0015975 neuplatňovat.},
title = {Endocrine-disrupting chemicals rapidly affect intercellular signaling in Leydig cells},
url = {https://www.sciencedirect.com/science/article/pii/S0041008X20303033?via%3Dihub},
volume = {404},
year = {2020}
}
TY - JOUR
ID - 1708556
AU - Yawer, Affiefa - Sychrová, Eliška - Labohá, Petra - Raška, Jan - Jambor, Tomas - Babica, Pavel - Sovadinová, Iva
PY - 2020
TI - Endocrine-disrupting chemicals rapidly affect intercellular signaling in Leydig cells
JF - Toxicology and applied pharmacology
VL - 404
IS - October 2020
SP - 1-17
EP - 1-17
PB - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN - 0041008X
N1 - CZ.02.1.01/0.0/0.0/18_046/0015975 neuplatňovat.
KW - Connexins
KW - Endocrine-disrupting chemicals
KW - Gap junctional intercellular communication
KW - Leydig cells
KW - Reproductive toxicants
KW - Steroidogenesis
UR - https://www.sciencedirect.com/science/article/pii/S0041008X20303033?via%3Dihub
L2 - https://www.sciencedirect.com/science/article/pii/S0041008X20303033?via%3Dihub
N2 - 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.
ER -
YAWER, Affiefa, Eliška SYCHROVÁ, Petra LABOHÁ, Jan RAŠKA, Tomas JAMBOR, Pavel BABICA and Iva SOVADINOVÁ. Endocrine-disrupting chemicals rapidly affect intercellular signaling in Leydig cells. \textit{Toxicology and applied pharmacology}. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020, vol.~404, October 2020, p.~1-17. ISSN~0041-008X. Available from: https://dx.doi.org/10.1016/j.taap.2020.115177.
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