Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene

Archana Laknaur, Terri Lee Foster, Lesley E. Bobb, Aramandla Ramesh, Gwinnett M. Ladson, Darryl B. Hood, Ayman Al-Hendy, Chandrasekhar Thota

Research output: Contribution to journalArticle

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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 NFκB-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 F 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.

Original languageEnglish (US)
Pages (from-to)827-835
Number of pages9
JournalJournal of Applied Toxicology
Volume36
Issue number6
DOIs
StatePublished - Jun 1 2016

Fingerprint

Long Evans Rats
Histone Deacetylases
Myometrium
Benzo(a)pyrene
Premature Birth
Rats
Cytokines
Prostaglandin-Endoperoxide Synthases
Uterus
Incidence
Rat control
Obstetrics
High pressure liquid chromatography
Pregnancy
Connexin 43
Polymerase chain reaction
Metaplasia
Hematoxylin
Eosine Yellowish-(YS)
Metabolites

Keywords

  • Benzo(a)pyrene
  • Connexin 43, Cox2
  • Environmental toxicant
  • Histone deacetylases
  • Inflammatory cytokines
  • NFκB
  • Preterm birth
  • Rats
  • Uterine myometrium

ASJC Scopus subject areas

  • Toxicology

Cite this

Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene. / Laknaur, Archana; Foster, Terri Lee; Bobb, Lesley E.; Ramesh, Aramandla; Ladson, Gwinnett M.; Hood, Darryl B.; Al-Hendy, Ayman; Thota, Chandrasekhar.

In: Journal of Applied Toxicology, Vol. 36, No. 6, 01.06.2016, p. 827-835.

Research output: Contribution to journalArticle

Laknaur, Archana ; Foster, Terri Lee ; Bobb, Lesley E. ; Ramesh, Aramandla ; Ladson, Gwinnett M. ; Hood, Darryl B. ; Al-Hendy, Ayman ; Thota, Chandrasekhar. / Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene. In: Journal of Applied Toxicology. 2016 ; Vol. 36, No. 6. pp. 827-835.
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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 NFκB-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.",
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AU - Bobb, Lesley E.

AU - Ramesh, Aramandla

AU - Ladson, Gwinnett M.

AU - Hood, Darryl B.

AU - Al-Hendy, Ayman

AU - Thota, Chandrasekhar

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