• Clinical and Experimental Reproductive Medicine
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• v.34 no.3
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• pp.149-157
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• 2007

Objective: This study was performed to compare the expression of osteopontin (OPN) mRNA and protein in the eutopic and ectopic endometrial tissues in women with endometriosis and endometrial tissues in women without endometriosis. Methods: A total of 32 women with histologically confirmed endometriosis were recruited for study group. For controls, 34 women undergoing operative treatment for cervical intraepithelial neoplasia (CIN) or benign gynecologic condition other than endometriosis were recruited. At the time of laparoscopy or laparotomy, a biopsy specimen was taken from the endometrial cavity and peritoneal endometrial implant or endometrioma whenever appropriate. We employed real time quantitative RT-PCR to quantify OPN mRNA expression of these tissues and performed western blot analysis to measure the quantity of OPN. Results: The expression of OPN mRNA was significantly higher in both eutopic and ectopic endometrial tissues of women with endometriosis than in endometrial tissues of controls during both proliferative and secretory phase. In the eutopic endometrial tissue of women with endometriosis, OPN mRNA expression significantly increased during the secretory phase compared to the proliferative phase in women with endometriosis as well as controls. However, in the ectopic endometrial tissue, OPN mRNA expression significantly decreased during the secretory phase compared to the proliferative phase. The expression of OPN protein was significantly higher in women with endometriosis than in controls. Conclusion: This study shows the marked expression of OPN mRNA and protein in eutopic and ectopic endometrial tissues in women with endometriosis may be associated with the adhesion and invasion of endometrial explants.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.159-168
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• 2010

Objective: The purpose of this study was to evaluate the correlation between the expression pattern of vascular endothelial growth factor (VEGF) in endometrium and the pathogenesis of endometriosis by investigating VEGF expression patterns and their difference between eutopic endometrium of patients with endometriosis and that of normal controls without endometriosis. Methods: Endometrial sections were obtained from 64 hysterectomy specimens from women under age of 40, who had undergone hysterectomies and had histological evidence of endometriosis, with stage 3 and 4 according to the revised American Society for Reproductive Medicine classification. As for controls, 37 sections were gained from women diagnosed as having cervical intraepithelial neoplasia (CIN) of the uterine cervix and without evidence of pelvic endometriosis or adenomyosis during their operation. The VEGF content was evaluated immunohistochemically in the eutopic endometrium from 64 patients with endometriosis and 37 normal controls. Histological semiquantitative score (H-score) was calculated and compared between study group and control group throughout the menstrual cycle. Results: There was no significant difference in the H-score of VEGF in the eutopic endometrium between patients with endometriosis and controls without endometriosis when compared according to the same phase of the cycle, although the H-score of the study group was significantly higher in the secretory phase than the proliferative phase. Conclusion: The VEGF expression in the eutopic endometrium of women with endometriosis was not different from that of women without endometriosis. This study suggests VEGF expression in eutopic endometrium is unlikely associated with the pathogenesis of endometriosis.

• Development and Reproduction
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• v.4 no.1
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• pp.101-108
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• 2000

Objectives: The pleiotrophin (PTN) and midkine (MK) are secreted heparin-binding neurokines that share 50％ sequence homology. PTN and MK are expressed in the range of primary human tumors. The association of PTN and MK with carcinogenesis, enhancement of plasminogen activator activity and angiogenic factor are reported. Patients with endometriosis are characterized by the ability of the endometrium to implant; angiogenic and growth factors may play a significant role in the pathogenesis of endometriosis. To test the hypothesis that higher expression of PTN and MK in endometrium from women with endometriosis might be increase angiogenesis and growth ectopic endometriosis implants, we investigated PTN and MK expression by quantitative and competitive polymerase chain reaction (QC-PCR) in endometrium from women with and without endometriosis throughout the menstrual cycle. Design: MK and PTN mRNA expression in endomeoium from women with endometriosis and control patients without endometriosis were determined by QC-PCR throughout the menstrual cycle. Methods: Endometrial tissue was obtained from 25 patients with severe endometriosis and 30 patients without endometriosis undergoing hysterectomy or endometrial biopsy. Stage of endometrial cycle and a diagnosis of endometriosis were confirmed histologically. Total RNA was extracted and reverse transcribed into c-DNA. QC-PCR was performed to evaluate PTN and MK mRNA expression. Results were analysed by Post Hoc test. Results: MK and PTN were expressed throughout the menstrual cycle in both groups. MK expression was higher in follicular phase than luteal phase in endometrium from normal women. endometrium from endometriosis patients showed increased expression of PTN and MK compared to endometrium from normal women in the luteal phase (p<0.05). Conclusion: Our results suggest that uterine endometrium from women with endometriosis expresses higher levels of MK and PTN than endometrium from normal women during luteal phase. Increased MK and PTN expression may be related to the initiation of ectopic endometrial implants and their subsequent peritoneal invasion.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.3
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• pp.199-205
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• 2006

Objective: The aim of this study was to evaluate the correlation between severity of endometriosis and the incidence of endometrial polyp. Methods: The study population consisted of six hundred thirty-one women who had undergone laparoscopic operation due to infertility, severe dysmenorrhea or ovarian tumors. We divided two groups: 434 women with endometriosis (study group) and 197 women without the disease (control group). The presence of endometriosis was documented by diagnostic or therapeutic laparoscopic operation and the disease severity was scored according to revised The American Fertility Society classification. We confirmed the endometrial polyps by pathologic examination after hysteroscopic polypectomy, and compared endometrial polyp incidence according to severity of endometriosis. Results: There was no significant difference between groups with regard to age, mean duration of infertility. Endometrial polyps were found in 274 women (63.0%) with endometriosis and in 58 controls (29.8%, p=0.0000). The incidence of endometrial polyps differed significantly according to stage of endometriosis. The incidence of endometrial polyps were 77/142 (54.2%), 58/90 (64.4%), 73/108 (67.6%, p<0.05), 66/94 (70.2%, p<0.05) in endometriosis stage I, II, III, and IV. There was a linear correlation between stage of endometriosis and endometrial polyps incidence (p=0.008). Conclusion: Endometriosis is accompanied by endometrial polyps. This results showed positive correlation between severity of the endometriosis and incidence of endometrial polyps. It is the possible mechanism for low pregnancy rate in the severe endometriosis.

• Clinical and Experimental Reproductive Medicine
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• v.34 no.4
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• pp.275-283
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• 2007

Objective: This study was performed to investigate the expressions of endometriosis related genes in shed endometrial tissues from menstrual blood of patients with or without endometriosis. Methods: The shed endometrial tissues were collected on 2$^{nd}$ or 3$^{rd}$ day of menstrual cycle with Wallace catheter in patients with endometriosis (n=16) and without endometriosis (n=26). The mRNA expressions of twelve kinds of endometriosis related genes were compared between two groups using semi-quantitative RT-PCR. Results: The collected shed endometrium was confirmed by histological observation. Expressions of telomerase, c-kit and aromatase mRNA were not detected by RT-PCR in shed endometrial tissues. The mRNA expressions of apoptosis related genes (fas, fas ligand, bcl-2, bax), stem cell factor, estrogen receptor-$\alpha$/$\alpha$, endometriosis protein-I and secretory leukocyte protease inhibitor gene were similar between shed endometrial tissues with endometriosis and without endometriosis. Conclusion: We could not find the difference of mRNA expressions of tested endometriosis related genes between shed endometrial tissues with or without endometriosis by semi-quantitative RT-PCR analysis. It may be related to the dynamical changes of gene expressions in the endometrium with menstrual cycle.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.4
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• pp.229-236
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• 2006

Objective: We investigated the expression of uPA and uPAR in eutopic endometrium of advanced stage endometriosis and control patients. Methods: The 33 endometriosis patients and 32 controls were enrolled. Endometrial samples were obtained from 65 premenopausal women aged 29-44 years, undergoing laparoscopic surgery or hysterectomy for non-malignant lesions. Sufficient samples were collected from 33 patients with endometriosis stage Ill and IV and 32 controls without endometriosis confirmed by laparoscopic surgery. The mRNA expression of uPA and uPAR from eutopic endometrium were analyzed by RT-QC PCR. Results: The mRNAs of uPA and uPAR were expressed in eutopic endometrium from endometriosis and normal controls throughout the menstrual cycle. Uterine endometrium from women with endometriosis expresses significantly (p<0.05) higher levels of u-PA mRNA than endometrium from normal women without endometriosis in the proliferative phase. There were no significant differences in expression of uPAR in eutopic endometrium between controls and endometriosis patients. Conclusion: These results suggest that eutopic endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation because of greater u-PA mRNA expression than endometrium from women without endometriosis. Thus, increased proteolytic activity may be one etiology for the invasive properties of the endometrium resulting in the development of endometriosis.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.1
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• pp.1-12
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• 2010

진단적 복강경을 하지 않으면 자궁내막증의 진단이 불가능하다는 점은 의사들이 해결해야 할 과제 중 하나이다. 아직까지는 자궁내막증을 진단할 수 있는 획기적인 표지자가 없기 때문에 CA-125 같은 종양 표지자의 혈중 농도를 측정하였으나 진단 도구로 이용하기에는 한계가 있다. 이러한 이유로 초기 자궁내막증을 진단할 수 있는 방법을 연구하기 위한 여러 시도들이 있었는데 특히 자궁내막증 1, 2기 환자에서 병의 초기 상태에 복강경적 치료를 하였을 경우 자연 임신 성공률이 2배 가까이 높은 것으로 보고되었기 때문에 불임 여성에 있어 자궁내막증의 진단 시기는 임상적으로도 그 중요성이 매우 크다고 할 수 있겠다. CA-125는 자궁내막증 환자의 추적관찰에 있어 특이도가 높은 편이며 효용성이 있는데 특히 수술적 치료 후 장기적으로 병의 활성 혹은 재발을 평가하는데 있어 유용하다. 무작위적인 임상 연구 결과 자궁내막증과 관련된 불임이나 통증은 수술적 치료시 분명한 이득이 있는 것으로 보고된 바84 자궁내막증은 적절한 진단과 치료가 중요한 질환이라는 점을 다시 한번 상기해야 한다. 또한 병의 진행에 따른 여러 면역학적인 변화들이 확인되면서 자궁내막증의 진단에 있어 면역학적 표지자의 중요성이 부각되고 있다. 그 중에서도 복막액이나 혈청 내 사이토카인은 진단 도구로서 그 가능성에 주목을 받고 있으며 이에 대한 대규모 연구가 추후 필요할 것으로 사료된다. 최근의 면역학적 발견과 DNA 기술 발전은 자궁내막증의 진단에 있어 핵심적인 screening 도구의 발견에 일조할 것이며 이러한 기술적 발전을 근간으로 하여 머지 않아 획기적인 표지자가 개발될 것으로 기대한다.

• Clinical and Experimental Reproductive Medicine
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• v.22 no.3
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• pp.227-240
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• 1995

착상은 정상적으로 발육한 건강한 배아와 자궁내막과의 만남으로 이루어진다. 따라서 착상을 이해하려면 배아의 발달 과정 및 배아가 착상시 극복해야 하는 정상적인 과정, 즉 배아와 자궁조직과의 접촉, 혈관 연결, 착상 내막 조직의 변화 및 모체 면역체계의 변화 등에 대한 이해가 필요하다. 배아에 염색체 이상 등이 동반되는 경우 건강한 signal로 자궁내막을 변화시킬 수 없으며 결과적으로 착상의 실패를 가져오게 된다. 착상과정에 있어 배아는 스스로의 정상적인 발달과정을 통하여 자궁내막의 변화를 일으킬 뿐 아니라, 또한 모체의 면역기전으로 부터 스스로를 보호할 능력을 갖추게 되므로 건강치 못한 배아는 자연도태된다.

• Development and Reproduction
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• v.3 no.1
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• pp.29-38
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• 1999

The pathogenesis of endometriosis is unknown, but retrograde menstruation is widely accepted as an etiology. Refluxed endometrium from endometriosis patients is more prone to implant and invade peritoneum possibly through the action of extracellular proteolysis. This proteolytic action may involve plasminogen activators and the collagenase system. Plasminogen activators (PAs) and matrix metalloproteinases (MMPs) play a critical role in the breakdown of extracellular matrix components and basement membrane in the processes of implantation and tumor invasion. PAs are inhibited by plasminogen activator inhibitor (PAI) and MMPs activity is inhibited by tissue inhibitor of metalloproteinase (TIMP). To test the hypothesis that lower expression of PAI-1 and TIMP-3 in endometrium from women with endometriosis, we investigated their PAI-1 and TIMP-3 expression by quantitative competitive RT PCR in endometrium from women with and without endometriosis. Endometrial tissues were obtained from 14 patients with severe endometriosis and 14 patients without endometriosis. Total RNA was extracted and reverse transcribed into cDNA, and quantitative competitive PCR (QC PCR) was performed to evaluate PAI-1 and TIMP-3 mRNA expression. Endometrium from patients with endometriosis showed decreased expression of PAI-1 and TIMP-3 mRNA compared to endometrium from control in luteal phase (p<0.05). Our results suggest that endometrium from women with endometriosis expresses lower levels of PAI-1 and TIMP-3 than endometrium from normal women. Endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation than control because of higher PA and MMP enzymatic activity. Thus, increased proteolytic activity may be one of the reasons for the invasive properties of the endometrium resulting in the development of endometriosis.

• Journal of Veterinary Clinics
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• v.32 no.5
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• pp.426-432
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• 2015

This study compared blood metabolites during peri- and postpartum periods among cows with clinical or subclinical endometritis and cows without endometritis. Blood samples from 207 Holstein dairy cows were collected at 4 weeks prepartum, just after calving, and at 1, 2, 4, and 6 weeks postpartum to measure serum concentrations of calcium, magnesium, non-esterified fatty acids (NEFAs), total cholesterol, albumin, urea nitrogen, ${\beta}$-hydroxybutyrate (BHBA), aspartate aminotransferase (AST), ${\gamma}$-glutamyltransferase, glucose, and phosphorus. Clinical endometritis was diagnosed by the observation of vaginal discharge (> 50% pus) and subclinical endometritis was diagnosed by the evaluation of uterine cytology (> 18% neutrophils) at 4 weeks postpartum. Cows were divided into three groups based on the presence or absence of clinical or subclinical endometritis: the control group (n = 104), the clinical endometritis group (n = 66), and the subclinical endometritis group (n = 37). Calcium and magnesium concentrations were lower in the clinical endometritis group than in the control and subclinical endometritis groups throughout the study period (p < 0.05 to 0.0001), whereas the NEFAs concentration was higher in the clinical endometritis group than in the control group throughout the study period (p < 0.01). The total cholesterol concentration was lower in the clinical endometritis group than in the control and subclinical endometritis groups throughout the pre- and postpartum periods (p < 0.05 to 0.001). The albumin concentration was lower in the clinical endometritis group than in the control and subclinical endometritis groups during the postpartum period (p < 0.05 to 0.001). The urea nitrogen concentration was lower in the clinical endometritis group than in the control and subclinical endometritis groups at 4 and 6 weeks postpartum (p < 0.01). At 1 week postpartum, the BHBA concentration was higher in the clinical endometritis group than in the control group (p < 0.05), whereas the AST concentration was higher in the clinical endometritis and subclinical endometritis groups than in the control group (p < 0.05). In conclusion, lower serum concentrations of calcium, magnesium, total cholesterol, albumin, and urea nitrogen, but higher concentrations of NEFAs, BHBA, and AST during the postpartum period were associated with the incidence of clinical endometritis, indicating the importance of balanced nutrition during the transition period.