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

作者：Laknaur Archana; Foster Terri Lee; Bobb Lesley E; Ramesh Aramandla; Ladson Gwinnett M; Hood Darryl B; Al Hendy Ayman; Thota Chandrasekhar^*

来源：Journal of Applied Toxicology, 2016, 36(6): 827-835.

DOI：10.1002/jat.3216

• Preterm birth
• Benzo(a)pyrene
• inflammatory cytokines
• connexin 43
• Cox2
• Histone deacetylases
• NF?B
• Environmental toxicant
• Rats
• Uterine myometrium

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 mu g 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 NF?B-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-1 and -8, tumor necrosis factor-, connexin 43, cyclo-oxygenase-2 and prostaglandin F-2 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 NFB-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 NFB pathway. Copyright (c) 2015 John Wiley & Sons, Ltd.
There are no studies on the role of benzo[a]pyrene (BaP), an environmental toxicant, on preterm birth. In this study, pregnant rats treated with BaP delivered prematurely. Histopathology performed on the uterus, postpartum day 22, showed structural abnormalities in BaP-exposed rats. We observed a direct correlation between BaP metabolites and expression of interleukin-1 and -8, tumor necrosis factor , connexin 43, cyclo-oxygenase-2, prostaglandin F-2 receptor, histone deacetylase 5 (P < 0.05) and nuclear NF?Bp65 and an inverse correlation with histone deacetylases 1 and 3 in the myometrium of BaP-exposed rats.

• 出版日期2016-6