Novel medicine and therapeutic effect for endometriosis using a mouse development model = 인간 자궁내막증 유사 동물모델을 이용한 새로운 치료제 발굴 및 효과에 대한 연구

다국어 초록 (Multilingual Abstract)

Endometriosis is often seen as a reproductive disease. It can impact reproductive organ of women, causing pelvic pain and subfertility. Current therapeutic medicines for endometriosis cannot be administered during ART because they have a bad influence on pregnancy. In this study, we made an animal model of endometriosis and evaluated therapeutic effect of progestin (Dienogest), dopamine agonist (Cabergoline) and combined (Dienogest + Cabergoline).
We prepared the animal model of endometriosis with C57BL mouse as recipient and ICR mouse as donor after surgical ovariectomy. Both donor and recipient mice were induced with estrogen priming. At 19 days after priming, endometrial fragment tissue extracted from the donor mouse was injected to the pelvic cavity of the recipient mouse. Mouse model of endometriosis was then treated with a single drug (Dienogest, Cabergoline) or combined drugs (Dienogest + Cabergoline) for 14 days. Immunohistological study was then performed to analyze inflammatory lesions of recipient mouse. RT-PCR and western blot were also performed to determine levels of genes and proteins in inflammatory lesions for the recovery of endometriosis.
Histologic staining images showed that all medication groups clearly decreased inflammatory phenotype in uterus, peritoneum, and intestine. Immunohistological study also showed that ER alpha showed stronger signals while ER beta and NGF showed weaker staining in single and combined medication groups. RT-PCR for gene expression analysis showed that ER beta, CCL2, CCL5, and IL6 showed decreased expression in all medication groups, and combined medication group was more decreased than single medication groups. Western blot for Protein expression showed that ER beta, NGF, and CD61 levels were decreased in all medication groups, and combined medication group was more decreased than single medication groups.
We established a mouse model mimicking human endometriosis. Cabergoline had similar therapeutic effect to Dienogest, could be used as an alternative of Dienogest during ART for patients with infertility, and combined medication has a synergic effect on endometriosis treatment compared to single medication.

목차 (Table of Contents)

• LIST OF TABLES ………………………………………………………… iii
• LIST OF FIGURES ……………………………………………………… iii
• ABSTRACT IN KOREAN ………………………………………………… iv
• I. INTRODUCTION …………………………………………… 1
• II. MATERIALS AND　METHODS ………………………… 5
• 1. Animals ………………………………………………………………… 5
• 2. In vivo model of endometriosis…………………………………… 5
• 3. Histological study……………………………………………………… 7
• 4. Immunohistochemistry study……………………………………… 7
• 5. RT-PCR for gene expression analysis………………………… 9
• 6. Western blotting for protein expression analysis……………10
• 7. Statistical analysis …………………………………………………… 11
• III. RESULTS ………………………………………………… 14
• 1. Gross findings of pelvic cavity…………………………………… 14
• 2. Histological study of endometriosis animal model………… 14
• 3. Immunohistochemistry data……………………………………… 15
• 4. Gene expression analysis by RT-PCR………………………… 15
• 5. Protein expression analysis by Western blot…………………16
• IV. DISCUSSION ……………………………………………… 27
• V. CONCLUSION ……………………………………………… 31
• REFERENCES ……………………………………………………………… 32
• ABSTRACT IN ENGLISH　……………………………………………… 40