Hirotaka Ota

Endothelial nitric oxide synthase in the endometrium during the menstrual cycle in patients with endometriosis and adenomyosis

OBJECTIVE To determine the expression of endothelial nitric oxide synthase in the endometrium during the menstrual cycle in endometriosis and adenomyosis. DESIGN Immunohistochemical identification of endothelial nitric oxide in endometrial tissues using the monoclonal antibody. SETTING Department of obstetrics and gynecology in a university hospital. PATIENT(S) The subjects were divided into three groups: 35 patients with endometriosis, 33 patients with adenomyosis proven histologically, and 46 fertile controls. MAIN OUTCOME MEASURE(S) Semiquantitative immunostaining (evaluation nomogram) score in endometrial cells. RESULT(S) The analyses revealed phase-dependent changes in the expression of endothelial nitric oxide synthase in the surface and glandular epithelia during the menstrual cycle in the fertile controls. The expression was weakest in the early proliferative phase, gradually increased, was most marked in the midsecretory phase, and decreased thereafter. In contrast, stromal cells did not change throughout the cycle. Contrary to expectations, the expression of endothelial nitric oxide synthase in endometriosis and adenomyosis was persistently greater than the control levels throughout the menstrual cycle. CONCLUSION(S) This study has shown that endothelial nitric oxide synthase is changed in a phase-dependent manner during the menstrual cycle. The exaggerated expression of endothelial nitric oxide synthase in the endometrium throughout the cycle suggests some pathologic role in endometriosis and adenomyosis.

Immunohistochemical assessment of superoxide dismutase expression in the endometrium in endometriosis and adenomyosis

OBJECTIVE To determine the expression of superoxide dismutase (SOD) in the endometrium during the menstrual cycle in endometriosis and adenomyosis. DESIGN Immunohistochemical identification of SOD in endometrial tissues using the monoclonal antibody. SETTING Department of obstetrics and gynecology in a university hospital. PATIENT(S) The subjects were divided into three groups: 36 patients with endometriosis, 38 patients with histologically proven adenomyosis, and 47 fertile control subjects. INTERVENTION(S) Endometrium was biopsied throughout the menstrual cycle. MAIN OUTCOME MEASURE(S) Semiquantitative immunostaining (evaluation nomogram) score for endometrial cells. RESULT(S) The analyses revealed phase-dependent changes in the expression of SODs in the glandular and surface epithelia during the menstrual cycle in fertile controls. Specifically, the expression of copper, zinc SOD was weakest in the early and midproliferative phases, then gradually increased, and was most marked in the early and midsecretory phases. The expression of manganese SOD reached a peak in the late secretory phase. The expression of both SODs in endometriosis and adenomyosis was persistently higher than the control levels throughout the menstrual cycle. CONCLUSION(S) The exaggerated expression of both SODs in the endometrium throughout the menstrual cycle suggests that superoxide plays a key role in infertility in endometriosis and adenomyosis.

Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis

OBJECTIVE To determine the expression of glutathione peroxidase (GPx) in the eutopic and ectopic endometria during the menstrual cycle in endometriosis and adenomyosis. DESIGN Immunohistochemical identification of GPx in endometrial tissues identified using the polyclonal antibody. SETTING Department of obstetrics and gynecology in a university hospital. PATIENT(S) One hundred fourteen women divided into three groups: 33 patients with endometriosis, 34 patients with adenomyosis, and 47 fertile control subjects. INTERVENTION(S) Endometrium biopsied throughout the menstrual cycle. MAIN OUTCOME MEASURE(S) Endometrial cells: semiquantitative immunostaining (evaluation nomogram) score. RESULT(S) The analyses revealed phase-dependent changes of GPx expression in the surface and glandular epithelia in the eutopic endometrium during the menstrual cycle in the fertile controls, i.e., the expression was weak in the early proliferative phase, gradually increased, was most marked in the early secretory phase, and decreased thereafter. The expression of GPx in the eutopic endometrium in endometriosis lost the variation during the menstrual cycle. The expression of GPx in adenomyosis was persistently marked over the control levels throughout the menstrual cycle. CONCLUSION(S) The aberrant expression of GPx in the eutopic endometrium throughout the cycle suggests a pathological role in endometriosis and adenomyosis.

Xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis

OBJECTIVE To investigate the expression of xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. DESIGN Immunohistochemical identification of xanthine oxidase in endometrial tissues by using polyclonal antibody. SETTING University hospital. PATIENT(S) Thirty-four women with endometriosis, 34 women with adenomyosis, and 44 fertile control women. INTERVENTION(S) Biopsy samples were obtained from the endometrium throughout the menstrual cycle. MAIN OUTCOME MEASURE(S) Semiquantitative immunostaining (evaluation nomogram) score of endometrial cells. RESULT(S) The level of xanthine oxidase expression in the glandular epithelium of control varied according to menstrual phase, but no such variation in expression was seen in endometriosis. Variation in xanthine oxidase expression was observed during the menstrual cycle in patients with adenomyosis; this variation differed completely from that in controls. Xanthine oxidase expression was found in ectopic endometrial tissue in all cases. The mean evaluation nomogram levels in the glandular epithelium in adenomyosis tissue were as high as those in the early secretory phase in the eutopic endometrium. CONCLUSION(S) Aberrant expression of xanthine oxidase in eutopic and ectopic endometrium appears to play a pathologic role in endometriosis and adenomyosis.

Distribution of heat shock proteins in eutopic and ectopic endometrium in endometriosis and adenomyosis

OBJECTIVE To evaluate the pathophysiologic role of heat shock proteins and to examine the effect of danazol on these proteins in patients with endometriosis and adenomyosis. DESIGN Immunohistochemical identification of human heat shock proteins 27, 60, and 70 in endometrial glandular cells identified using monoclonal antibodies. SETTING Department of obstetrics and gynecology in a university hospital. PATIENT(S) Subjects were 119 women with documented endometriosis or adenomyosis. The subjects were divided into three groups: fertile control (n = 38), with 14 in the proliferative phase and 24 in the secretory phase; endometriosis (n = 38); and adenomyosis (n = 43), including 33 who underwent hysterectomy and 10 treated with danazol. MAIN OUTCOME MEASURE(S) Staining of glandular cells by semiquantitative immunostaining (evaluation nomogram) score. RESULT(S) Significantly increased expression of heat shock protein 27 was noted in eutopic endometrium from patients with endometriosis and adenomyosis as compared with controls, regardless of the menstrual phase. The scores for heat shock protein 27 and heat shock protein 70 in the ectopic endometrium of patients with endometriosis were low compared with those in eutopic endometrium, whereas in adenomyosis, the scores were similar to those of eutopic endometrium. After treatment with danazol, the expression of heat shock proteins returned to control levels. CONCLUSION(S) We suggest that abnormally increased expression of heat shock proteins plays a role in the pathophysiology of endometriosis and adenomyosis.

Expression of major histocompatibility complex class II antigen in endometriotic tissue in patients with endometriosis and adenomyosis

OBJECTIVE To evaluate the expression of major histocompatibility complex class II antigen (human leukocyte antigen, HLA-DR) in glandular cells in eutopic and ectopic endometria in patients with endometriosis and adenomyosis. PATIENTS Subjects consisted of 50 patients with adenomyosis and 18 patients with endometriosis. Controls consisted of 17 patients with adenomyoma and 42 infertile women without habitual abortion and autoimmune diseases. DESIGN Glandular cells in eutopic and ectopic endometria were analyzed immunohistochemically to localize the expression of HLA-DR antigen. The sections were scored from 0 to 5 according to the evaluation nomogram. RESULTS Immunohistochemical analysis revealed significantly increased expression of HLA-DR antigen in the glandular cells in eutopic and ectopic endometria, compared with materials from patients with adenomyoma and infertile patients. CONCLUSIONS It is likely that aberrant expression of HLA-DR antigen in glandular cells of eutopic and ectopic endometria in endometriosis and adenomyosis is deeply involved in various immunological abnormalities.

Integrin Adhesion Molecules in the Endometrial Glandular Epithelium in Patients with Endometriosis or Adenomyosis

Objective: To assess the role of β1 ‐integrin and E‐cadherin molecules in the eutopic glandular epithelium in patients with endometriosis or adenomyosis.

Laparoscopy-assisted Ruge procedure for the creation of a neovagina in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome

OBJECTIVE To describe the successful use of a laparoscopy-assisted Ruge procedure for the reconstruction of a vagina in a patient with Mayer-Rokitansky-Küster-Hauser syndrome. DESIGN Case report. SETTING A university hospital. PATIENT(S) A 19-year-old Japanese woman with Mayer-Rokitansky-Küster-Hauser syndrome. INTERVENTION(S) Creation of a neovagina by a laparoscopy-assisted Ruge technique. MAIN OUTCOME MEASURE(S) Clinical examinations were performed during the follow-up period. The depth and diameter of the neovagina were measured by vaginography. Patient satisfaction also was determined. RESULT(S) The neovagina was 12 cm in length and 4 cm in diameter. The mucosa of the neovagina was pinkish and had a moist surface. No intraoperative or postoperative complications were observed. CONCLUSION(S) The use of an isolated segment of the sigmoid colon for vaginal construction has the advantages of providing a sufficient length of neovagina and not requiring immediate postoperative self-dilatation. We believe that our procedure has various advantages in addition to those of the original Ruge method, including its minimally invasive nature and excellent cosmetic results. Further, a laparoscopy-assisted operation allows for the diagnosis of uterine defects and the creation of a neovagina at the same time.

Endometriosis and Free Radicals

Recent studies have shown that synthase for nitric oxide or scavenger enzymes is distributed throughout the endometrium. We have reported that endothelial nitric oxide synthase, originally identified in vascular endothelial cells, is distributed in glandular epithelial cells in the endometrium, peaking in the midsecretory phase. In addition, it is known that superoxide dismutase is distributed throughout the endometrium, varying with the menstrual cycle. Yet it is not clear how these enzymes are committed in the reproductive processes. Endometriosis is often complicated by infertility and miscarriage. Of particular interest is that these enzymes are overexpressed in the disease throughout the menstrual cycle. These findings strongly suggest that excessive amounts of free radicals are produced in endometriosis.

Effects of danazol at the immunologic level in patients with adenomyosis, with special reference to autoantibodies: A multi-center cooperative study

OBJECTIVE We attempted to evaluate the effects of danazol on autoantibodies, in particular, to phospholipids, and on the immune system in patients with adenomyosis. STUDY DESIGN Forty-two patients with adenomyosis who had high titers of autoantibodies were randomly chosen, and they received 400 mg/day of danazol for 4 months (n = 22) or underwent hysterectomy (n = 20). RESULTS Among the six autoantibodies we investigated, the incidence of antiphosphatidylinositol immunoglobulin G was the highest (42.9%), followed by antiphosphatidylglycerol immunoglobulin G (38.1%). The autoantibody titers decreased with time and were comparable to the control values 16 weeks after treatment in both groups. Total serum levels of immunoglobulin G and M were high before treatment, but immunoglobulin M levels decreased significantly in week 8 during treatment with danazol, whereas C4 levels increased and C3 levels decreased with danazol. CONCLUSION Danazol has an inhibitory effect on the autoimmunologic response associated with adenomyosis.