초록

본 연구는 자궁내막증 환자의 체내에서 내분비교란물질의 농도가 증가되어 있는지를 검증하고 세포배양 및 누드마우스 모델에서 이들이 자궁내막증의 성립을 가능하게 하는지 검증할 목적으로 시행되었다. 연구 결과 자궁내막증 환자에서 중요한 내분비교란물질인 DEHP, MEHP가 대조군보다 유의하게 증가되어 있었고 또 세포배양 조건에서 DEHP의 투여가 혈장결핍 조건과 hydrogen peroxide 노출 후 조건에서 자궁내막 세포의 생존, 성장을 항진시킴으로써 궁극적으로 자궁내막증의 발병시킬 수 있다는 가설을 입증할 수 있었다.

Abstract ▼

BACKGROUND: Phthalates have been used as additives in industrial products and considered to be important endocrine disruptors. Based on the hypothesis that environmental factors play a critical role in the pathogenesis of endometriosis, several studies have shown that plasma level of di-(2-ethylhexy

BACKGROUND: Phthalates have been used as additives in industrial products and considered to be important endocrine disruptors. Based on the hypothesis that environmental factors play a critical role in the pathogenesis of endometriosis, several studies have shown that plasma level of di-(2-ethylhexyl) phthalate (DEHP) is elevated in women with endometriosis. However, there has been no study evaluating the effects of DEHP on endometrial cells.
METHODS: Following in vitro cell culture and treatment with DEHP, viability of endometrial cell was investigated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescent activated cell sorter (FACS) analysis, and microscopic evaluation after . We also evaluated whether the plasma concentrations of phthalate esters are elevated in women with advanced stage endometriosis in a Korean population utilizing liquid chromatography-tandem mass spectrometry.
RESULTS: MTT assay revealed that in vitro treatment with DEHP in serum-free condition for 3 days led to increased viability in Ishikawa cells and endometrial stromal cells. Following exposure to hydrogen peroxide, the DEHP groups also showed higher viability compared to the controls in both cell types. On FACS analysis after annexin V and propidium iodide staining following exposure to hydrogen peroxide, the percentage of live cells was higher in the DEHP groups in both cell types. More cells were left attached following exposure to hydrogen peroxide in the DEHP groups in both cell types on fluorescence microscopic evaluation after Hoechst staining. The plasma levels of mono-ethylhexyl phthalate (MEHP) as well as DEHP were significantly higher in the endometriosis group than the control group. Adjusting for other factors utilizing logistic regression model, the MEHP level and the BMI were found to be significantly associated with endometriosis.
CONCLUSIONS: Our results strongly suggest that plasma concentrarions of phthalate esters are increased in women with advanced stage endometriosis and that higher levels of phthalate esters might play a critical role in the establishment of endometriosis through increased viability of endometrial cells.

목차 Contents

• 1. 겉표지 ...1
• 2. 제출문 ...3
• 3. 보고서 요약서 ...4
• 4. 요약문 (한글) ...5
• 5. 요약문 (영문) ...6
• 6. 연구 성과 실적 및 향후 계획 ...7
• 7. 참여연구원 현황표 ...11
• I. 총괄연구과제 연구결과 ...12
• 1. 연구개발과제의 배경 및 필요성 ...13
• 2. 국내외 기술개발 현황 ...16
• 3. 연구개발과제의 추진체계 ...18
• 4. 연구개발수행 내용 및 결과 ...18
• 5. 목표달성도 및 관련분야 기여도 ...24
• 6. 향후 연구성과 추진 계획: 해당사항 없음 ...25
• 7. 연구개발결과의 파급효과 ...25
• 8. 연구개발결과의 활용계획 ...26
• 9. 연구개발과정에서 수집한 해외과학기술정보: 해당사항 없음 ...26
• 10. 참고문헌 ...26
• II. 첨부서류 ...28
• 실적증빙자료 및 첨부서류 목차 ...29
• 1. 자체평가의견서 ...30
• 2. 실적 증빙자료 ...33
• 3. 기타 첨부서류 ...36