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17β‐Estradiol and Bisphenol‐A Exacerbate Symptoms of Dextran Sodium Sulfate Induced Colitis in Mice
Author(s) -
DeLuca Jennifer A.A.,
Allred Kimberly F.,
Jayaraman Arul,
Allred Clinton D.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1023.11
Subject(s) - medicine , colitis , inflammatory bowel disease , estrogen , ulcerative colitis , xenoestrogen , endocrinology , endocrine system , estrogen receptor , endocrine disruptor , gastroenterology , hormone , disease , breast cancer , cancer
Inflammatory bowel diseases (IBDs) are a collection of chronic disorders associated with inflammation of gastrointestinal (GI) epithelium and autoimmune responses in the GI tract. Crohn's disease (CD) and ulcerative colitis (UC), the two main IBDs, have differing responses to increased concentrations of estrogen in women suffering from these conditions. Evidence suggests that higher estrogen exposure, such as that associated with hormone replacement therapy or normal fluctuations during menses, are related to symptom reduction in women with CD but exacerbation of symptoms in those with UC. In the Dextran Sodium Sulfate (DSS) induced model of colitis, co‐administration of estrogen has previously shown negative effects on disease activity scores in mice. The effects of xenoestrogens on DSS‐induced colitis have not been evaluated. One such xenoestrogen, Bisphenol‐A (BPA), is a known endocrine disruptor with estrogenic effects mainly via estrogen receptor β, the dominant estrogen receptor in the GI tract. In this study, we investigated the ability of 17β‐estradiol (E 2 ) and BPA, to exacerbate colonic inflammation due to acute DSS‐induced colitis in vivo . Co‐treatment of DSS and E 2 resulted in 100% mortality, with initial deaths observed 72 hours after the start of DSS treatment. DSS and BPA together resulted in 67% mortality, with most deaths between 120 and 168 hours after initial DSS treatment. Body weight, an overall indicator of disease severity, decreased significantly in E 2 mice. BPA treatment also decreased body weight, with initial decrease occurring later than that observed in E 2 mice. Rectal bleeding scores were most severe in E 2 mice, with the greatest increase in severity between 48 and 72 hours following initiation of DSS. Between 48 and 120 hours after DSS treatment began, rectal bleeding scores of BPA mice worsened and were intermediate between E 2 and control mice. Fecal consistency scores were most severe in E 2 mice. Fecal scores tended to be worse in BPA mice compared to controls, but this was not significant. DSS treatment significantly decreased colon length, as expected. Ongoing analysis focuses on evaluation of cytokine expression and pathological examination of tissues. This is the first study to demonstrate that a xenoestrogen introduced through the diet can exacerbate symptoms of UC and suggests that investigating how exposure to BPA might influence UC in humans is warranted. Support or Funding Information Funding was provided by the Center for Translational Environmental Health Research through National Institute of Environmental Health Sciences grant number P30ES023512.