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HERO ID
3224992
Reference Type
Journal Article
Title
Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene
Author(s)
Laknaur, A; Foster, TL; Bobb, LE; Ramesh, A; Ladson, GM; Hood, DB; Al-Hendy, A; Thota, C
Year
2016
Is Peer Reviewed?
Yes
Journal
Journal of Applied Toxicology
ISSN:
0260-437X
EISSN:
1099-1263
Publisher
WILEY
Location
HOBOKEN
Volume
36
Issue
6
Page Numbers
827-835
Language
English
PMID
26358852
DOI
10.1002/jat.3216
Web of Science Id
WOS:000374382700007
URL
https://www.proquest.com/docview/1781532556?accountid=171501&bdid=13857&_bd=ekAw9aa6jKKI%2B2A7JDBqUVABkIU%3D
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Abstract
Etiology of preterm birth (PTB) is multifactorial; therefore, decreasing the incidence of PTB is a major challenge in the field of obstetrics. Epidemiological studies have reported an association between toxicants and PTB. However, there are no studies on the role of benzo[a]pyrene (BaP), an environmental toxicant, in the incidence of PTB. We first assessed the effects of BaP (150 and 300 µg kg(-1) body weight) dosed via gavage from day 14 to 17 of pregnancy on gestation length in Long Evans rats. We further assessed the histopathology of the uterus, expression of inflammatory cytokines, contractile-associated factors, histone deacetylases (HDACs) and NFқB-p65 in myometrium collected on day 22 postpartum versus vehicle-treated controls. In our study, rats exposed to BaP delivered prematurely (P < 0.05) compared to control. Hematoxylin and eosin staining of uterus showed squamous metaplasia, glandular and stromal hyperplasia in BaP-exposed rats versus control. The concentrations of BaP metabolites measured by high-pressure liquid chromatography were higher in uterine myometrium of BaP-exposed rats while they were undetectable in controls. Quantitative real-time polymerase chain reaction showed significant increases in mRNA expression of interleukin-1β and -8, tumor necrosis factor-α, connexin 43, cyclo-oxygenase-2 and prostaglandin F2α receptor as compared to controls (P < 0.05). Western blot analysis revealed that BaP exposure caused decreases in class I HDACs 1 and 3 and increases in class II HDAC 5, cyclo-oxygenase-2 and nuclear translocation of NFκB-p65 relative to controls. Our results suggest that gestational exposure to BaP increases incidence of PTB through epigenetic changes that causes increases in the expression of contractile-associated factors through the NFκB pathway. Copyright © 2015 John Wiley & Sons, Ltd.
Keywords
Preterm birth; Benzo(a)pyrene; inflammatory cytokines; connexin 43; Cox2; Histone deacetylases; NF?B; Environmental toxicant; Rats; Uterine myometrium
Tags
IRIS
•
Benzo(a)pyrene (BaP)
August 2016 Update
Animal Studies
NAAQS
•
LitSearch-NOx (2024)
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