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Citation
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HERO ID
3984521
Reference Type
Journal Article
Title
Aroclor1254 disrupts the blood-testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway
Author(s)
Jia, X; Xu, Y; Wu, W; Fan, Y; Wang, G; Zhang, T; Su, W
Year
2017
Is Peer Reviewed?
Yes
Journal
Cell Death & Disease
ISSN:
2041-4889
Volume
8
Issue
5
Page Numbers
e2823
Language
English
PMID
28542131
DOI
10.1038/cddis.2017.224
Web of Science Id
WOS:000402195700072
Abstract
The blood-testis barrier (BTB) constituted by coexisting junction apparatus between Sertoli cells (SCs) plays an important role in spermatogenesis, which is a known target of various environmental toxicants. The commercial polychlorinated biphenyls mixture, Aroclor1254, has been shown to impair male reproduction by decreasing sperm count and affecting SC metabolism. This study was designed to investigate the effects of Aroclor1254 on the BTB integrity and elucidate the underlying mechanisms. We found that Aroclor1254 treatment in rats (1 or 3 mg/kg per day for 21 consecutive days) and in primary cultured SCs (5 or 10 μg/ml for 48 h) could induce BTB disruption via p38 MAPK pathway, concurrently with increments in junction proteins (JAM-A, N-cadherin, and β-catenin) endocytosis, and occludin ubiquitination. Either inhibition of caveolin-dependent membrane protein internalization by cholesterol oxidase or silencing E3 ubiquitine ligase Itch by small interfering RNA could partially counteract the effects of Aroclor1254 on the barrier function of cultured SCs. These results demonstrate that Aroclor1254 disrupts the BTB function by promoting the caveolin-dependent endocytosis and ubiquitine-proteasome degradation of junction proteins through the p38 MAPK pathway, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.
Tags
IRIS
•
PCBs
Mechanistic
Supplemental
Litsearches
LitSearch: August 2016-August 2017
PubMed
Toxline
WoS
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