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HERO ID
710825
Reference Type
Journal Article
Title
Arsenic induced progesterone production in a caspase-3 dependent manner and changed redox status in preovulatory granulosa cells
Author(s)
Yuan, XH; Lu, CL; Yao, N; An, LS; Yang, BQ; Zhang, CL; Ma, X
Year
2012
Is Peer Reviewed?
Yes
Journal
Journal of Cellular Physiology
ISSN:
0021-9541
EISSN:
1097-4652
Volume
227
Issue
1
Page Numbers
194-203
Language
English
PMID
21391215
DOI
10.1002/jcp.22717
Web of Science Id
WOS:000297942500021
Abstract
Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cAMP or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle stimulating hormone (FSH). GSH depletion with buthionine sulfoximine (BSO) led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3 dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment. © 2011 Wiley Periodicals, Inc.
Tags
•
Arsenic Hazard ID
1. Initial Lit Search
PubMed
WOS
ToxNet
4. Considered through Oct 2015
5. Additions through Oct 2015
6. Cluster Filter through Oct 2015
iAs MOA Literature Categorization
Cytotoxicity and Regenerative Proliferation
Immune
•
Arsenic (Inorganic)
1. Literature
PubMed
Toxline, TSCATS, & DART
Web of Science
4. Adverse Outcome Pathways/Networks Screening
Relevant
•
Arsenic MOA
4. Adverse Outcome Pathways
Endocrine mechanisms
5. Health Effect
Reproductive System Effects including Pregnancy Outcomes
1. MOA Literature Screening
MOA Cluster
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