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DNA methylation alterations in an association between bisphenol A and endometrial condition
비스페놀 A와 자궁내막질환의 연관성에서 DNA 메틸화 변이의 역할

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Authors
이선영
Advisor
정해원
Major
보건대학원 보건학과
Issue Date
2015-08
Publisher
서울대학교 보건대학원
Keywords
bisphenol Aendometriumendometrial cellsendometriosismyomaadenomyosisendometrial polypDNA methylationHOXA 10
Description
학위논문 (박사)-- 서울대학교 보건대학원 : 보건학과 분자역학전공, 2015. 8. 정해원.
Abstract
Bisphenol A is one of the endocrine disrupting chemicals and extensively used as protective coatings on food-storage containers, baby bottles, bottle tops, water pipes, and medical equipment. Bisphenol A binds to estrogen receptors, and acts as an estrogen agonist. Bisphenol A also induces epigenetic modifications. Endometrium expressed estrogen receptors, thus it could be a target tissue for bisphenol A. Several studies explored relationship between bisphenol A and gynecologic disorders. However, there are few studies about cytotoxic and epigenetic effects of bisphenol A on endometrium. Therefore, it is necessary to evaluate the relationships between bisphenol A and endometrial disorders.
This study evaluated cytotoxicity and DNA methylation changes in bovine endometrial cells induced by bisphenol A. And urinary bisphenol A concentrations were assessed from women with endometrial disorders, then the relationship was explored between urinary bisphenol A levels and methylation levels of endometrial tissue DNA.
When bovine endometrial cells were treated with 100 μM of bisphenol A for 3 h, the cell viability was significantly decreased. Also, apoptotic cells were significantly induced after 24 h treatment of bisphenol A at 100 μM. S phase arrest was observed after 3 h treatment, and G2/M cell cycle arrest was observed after 24 h treatment. After 1 h treatment, intracellular ROS was significantly increased. DNA damage was induced after 3 h treatment of bisphenol A. After 3 h treatment, global DNA methylation and HOXA 10 methylation levels were decreased. Meanwhile, the methylation level of RASSF1A, one of tumor suppressor genes, was increased after 24 h treatment of 100 μM bisphenol A.
Endometrial tissue DNAs were obtained from 44 women with endometriosis, myoma, or adenomyosis. The relationships between urinary bisphenol A and DNA methylation levels, and the diseases and DNA methylation status were evaluated. There were no significant differences about urinary bisphenol A level among the diseases, also the relationships between urinary bisphenol A levels and DNA methylation status were not observed. However, global DNA methylation level in proliferative phase was significantly higher than that in secretory phase. Sat2 methylation level was significantly higher in adenomyosis than that in myoma. Also, HOXA 10 methylation was significantly associated with endometrial polyps.
In conclusion, bisphenol A can induce cytotoxicity and modify DNA methylation level in bovine endometrial cells. The relations between urinary bisphenol A concentration and endometrial disorders, or urinary bisphenol A concentration and DNA methylation could not find in the epidemiologic study. On the other hand, global DNA hypomethylation was associated with endometrium phase, and endometrial polyps showed HOXA 10 hypermethylation. Therefore, HOXA 10 methylation can be used as a biomarker for endometrial polyp.
Language
English
URI
https://hdl.handle.net/10371/120789
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Graduate School of Public Health (보건대학원)Dept. of Public Health (보건학과)Theses (Ph.D. / Sc.D._보건학과)
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