Abstract:
BACKGROUND:Bisphenol A (BPA) is known to be biologically active in experimental models even at low levels of exposure. However, its impact on endometrial cancer remains unclear. OBJECTIVES:This study aimed to investigate whether lifelong exposure to different doses of BPA induced uterine abnormalities and molecular changes in a rat model. METHODS:Sprague-Dawley rats were exposed to 5 doses of BPA [0, 25, 250, 2,500, or 25,000 μ g / kg body weight (BW)/d] or 2 doses of 17 α - ethynylestradiol (EE2) (0.05 and 0.5 μ g / kg BW/d) starting from gestational day 6 up to 1 y old according to the CLARITY-BPA consortium protocol. The BW, uterus weight, and histopathology end points of the uteri were analyzed at postnatal (PND) day 21, 90, and 365. Estrous cycling status was evaluated in PND90 and PND365 rats. Transcriptomic analyses of estrus stage uteri were conducted on PND365 rats. RESULTS:Based on the analysis of the combined effects of all testing outcomes (including immunohistological, morphological, and estrous cycle data) in a semiblinded fashion, using statistical models, 25 μ g / kg BW/d BPA [BPA(25)], or 250 μ g / kg BW/d BPA [BPA(250)] exerted effects similar to that of EE2 at 0.5 μ g / kg BW/d in 1-y-old rats. Transcriptome analyses of estrus stage uteri revealed a set of 710 genes shared only between the BPA(25) and BPA(250) groups, with 115 of them predicted to be regulated by estradiol and 57 associated with female cancers. An interesting finding is that the expression of 476 human orthologous genes in this rat BPA signature robustly predicted the overall survival ( p = 1.68 × 10 - 5 , hazard ratio = 2.62 ) of endometrial cancer patients. DISCUSSION:Lifelong exposure of rats to low-dose BPA at 25 and 250 μ g / kg BW/d altered the estrous cycle and uterine pathology with similarity to EE2. The exposure also disrupted a unique low-dose BPA-gene signature with predictive value for survival outcomes in patients with endometrial cancer. https://doi.org/10.1289/EHP6875.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Leung YK,Biesiada J,Govindarajah V,Ying J,Kendler A,Medvedovic M,Ho SMdoi
10.1289/EHP6875subject
Has Abstractpub_date
2020-12-01 00:00:00pages
127005issue
12eissn
0091-6765issn
1552-9924journal_volume
128pub_type
杂志文章abstract:BACKGROUND:Humans living near industrial point emissions can experience high levels of exposures to air pollutants. Map Ta Phut Industrial Estate in Thailand is the location of the largest steel, oil refinery, and petrochemical factory complexes in Southeast Asia. Air pollution is an important source of oxidative stres...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0900907
更新日期:2010-01-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7519
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pub_type: 杂志文章
doi:10.1289/ehp.9337
更新日期:2006-10-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 历史文章,杂志文章
doi:10.1289/ehp.834913
更新日期:1983-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.95103s6243
更新日期:1995-09-01 00:00:00
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.00108s4625
更新日期:2000-08-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.95103s335
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP3169
更新日期:2019-05-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.99107539
更新日期:1999-07-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.751171
更新日期:1975-06-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:2002-02-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.939957
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9399307
更新日期:1993-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
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更新日期:1984-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.11590
更新日期:2009-03-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1289/ehp.02110s4573
更新日期:2002-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.1205281
更新日期:2013-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8353169
更新日期:1983-11-01 00:00:00
abstract::Polychlorinated biphenyls (PCBs) are important environmental contaminants, and their toxicity to wildlife and humans are of major concern. PCBs form persistent and abundant metabolites, PCB methyl sulfones, that accumulate in biota. We now report that certain hydroxylated PCB metabolites show a strong and selective ac...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102464
更新日期:1994-05-01 00:00:00
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doi:10.1289/ehp.1307459
更新日期:2014-04-01 00:00:00
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doi:10.1289/EHP1289
更新日期:2018-01-11 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.866593
更新日期:1986-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8763
更新日期:2006-06-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
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更新日期:1984-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.1409014
更新日期:2015-11-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8350149
更新日期:1983-04-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP2427
更新日期:2018-07-23 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9399265
更新日期:1993-03-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:1998-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.01109s4479
更新日期:2001-08-01 00:00:00