It is well known that the number of peritoneal macrophages is increased in patients with pelvic endometriosis. We measured the concentration of monocyte chemoattractant protein-1 (MCP-1) using an enzyme-linked immunosorbent assay (ELISA) in the peritoneal fluid of women with and without endometriosis. The expression of MCP-1 in pelvic endometriotic lesions obtained from the peritoneum was also examined using immunohistochemistry and nonradioactive in situ hybridization. The mean concentration of MCP-1 in the peritoneal fluid was significantly higher in the patients with endometriosis (P<0.05). The most significant elevation, compared with non-endometriosis patients, was found in stage I of the disease (P<0.05). However, no statistically significant difference was found among endometriosis stages I, II, III, and IV. Immunohistochemical staining revealed that MCP-1-positive cells were localized in the glandular epithelium of the endometriotic lesions and in the stromal macrophages distributed in those lesions, but normal peritoneal cells were negative. The in situ hybridization method demonstrated expression of MCP-1 mRNA on the endometriotic glandular epithelium and stromal macrophages. These findings suggest that MCP-1 may be involved in the histogenesis and early development of peritoneal endometriosis.

Female gonadotroph adenomas with endocrinological symptoms are uncommon. Six cases of such adenomas have been reported in the literature: two were girls who presented with precocious puberty and four were premenopausal women with accompanying multiple ovarian cysts. We describe here a 10-year-old Japanese girl with a gonadotroph macroadenoma and present detailed morphological findings of the tumor. The patient's chief complaints were nausea, abdominal distention, and abdominal pain. Abdominopelvic ultrasonography and magnetic resonance imaging (MRI) revealed bilateral multiple ovarian cysts. Endocrinological assays showed elevated serum follicle-stimulating hormone (FSH) (33.7 mIU/ml) and estradiol (3840 pg/ml). MRI of the head showed a large pituitary tumor. Two transsphenoidal operations and subsequent radiation therapy were performed. Immunohistochemically, more than half the tumor cells were positive for anti-FSH-β monoclonal antibody. Ultrastructurally, the tumor cells exhibited a fairly uniform picture of rounded cells. Their nuclei were slightly irregular and contained heterochromatin, and their cytoplasm contained many round, dense core granules, measuring 140–260 nm in diameter, together with well-developed organelles. An in vitro study showed that the tumor cells in primary culture produced FSH (1089.0 mIU/ml). To our knowledge, this is the first immunohistochemical and ultrastructural study of an FSH-secreting gonadotroph adenoma occurring in childhood.

Primary vaginal stones are extremely rare, particularly in young women. We describe the occurrence of a primary vaginal calculus in a severely retarded 11-year-old girl who was not diagnosed until she was examined using computerized tomography. We postulate that the calculus was formed as a consequence of urinary contamination of the vagina in association with incontinence and prolonged maintenance in a recumbent posture.

Objective: To develop an in vitro experimental model of ovarian endometriosis using human cells and to investigate the pathogenesis of endometriosis.Design: Controlled in vitro coculture study.Setting: A department of obstetrics and gynecology at a university hospital.Patient(s): Ovaries and endometrium were obtained from patients who underwent a hysterectomy because of gynecologic disease.Intervention(s): Human ovarian surface epithelial (OSE) cells were cultured alone and OSE cells and endometrial stromal (ES) cells were cultured together in a three-dimensional collagen gel culture system with or without the addition of E-2.Main Outcome Measure(s): The aggregated collagen gels containing the cultured cells were examined morphologically.Result(s): The OSE cells in single culture with E-2 formed circular arrangements. These cells were immunohistochemically positive for cytokeratin but negative for epithelial membrane antigen. In the cocultures of OSE and ES cells with E-2, the OSE cells formed a lumen structure surrounded by ES cells. Immunoreactivity for cytokeratin and epithelial membrane antigen was detected in the glandular cells and cilia were identified on the cell surface by electron microscopy. Without the addition of E-2, no structures were detected.Conclusion(s): A new in vitro experimental model was established with the aid of human OSE cells. Endometriotic lesions can arise through a process of metaplasia from OSE cells in the presence of E-2 and ES cells. (C) 1998 by American Society for Reproductive Medicine.

Ultrastructure studies of pelvic peritoneal tissue from women undergoing laparotomy suggest that before endometriosis has become established in the peritoneum, there might be a metaplastic change by peritoneal mesothelial cells into endometrial glandular cells. A new in vitro experimental model of endometriosis using human ovarian surface epithelium cells has shown evidence that endometriotic lesions can arise by a process of metaplasia from the ovarian surface epithelium. In this model, when both ovarian surface epithelium and ovarian stromal cells were cocultured with 17β estradiol in a three-dimensional collagen gel lattice, the ovarian surface epithelium cells formed a lumen structure, surrounded by endometrial stromal cells with an epithelial mesenchymal structure. Immunoreactivity for epithelial membrane antigen and cytokeratin was shown in the glandular cells and cilia, as well as in the microvilli. Electron microscopy showed evidence of tight junctions on cell surfaces. These findings suggest that endometriosis may manifest as a serial change from the adjacent mesothelial cells.

Objective: To elucidate the regulation and involvement of interleukin (IL)-1β, IL-8, and IL-1 receptor antagonist in the hCG-induced rabbit ovulatory process.

Objective: To elucidate the regulation and involvement of interleukin (IL)-1 beta, IL-8, and IL-1 receptor antagonist in the hCG-induced rabbit ovulatory process.Design: Randomized, controlled animal study.Setting: University research laboratory.Animal(s): Mature female New Zealand white rabbits.Intervention(s): After IV administration of 100 IU of hCG to rabbits, ovarian levels of IL-1 beta, IL-8, and IL-1 receptor antagonist were determined at indicated times by ELISA. Anti-IL-1 beta, anti-IL-8, or anti-IL-1 receptor antagonist antiserum was given IV 30 minutes before hCG injection.Main Outcome Measure(s): Effects of each antiserum oil the levels of the other cytokines and neutrophil accumulation, assessed by myeloperoxidase activity, were determined. Ovulation rate (rate of ruptured follicles) was also evaluated.Result(s): The maximal level of IL-8 was detected at 4 hours, which preceded that of IL-1 beta and IL-1 receptor antagonist, detected at 6 hours after hCG injection. Administration of anti-IL-1 beta antiserum resulted in a statistically significant reduction of the peak levels of IL-8 and IL-1 receptor antagonist. Administration of anti-IL-8 antiserum reduced the accumulation of IL-1 beta and IL-1 receptor antagonist. Anti-IL-1 receptor antagonist antiserum significantly augmented the accumulation of IL-1 beta and IL-8. Myeloperoxidase activity was reduced by anti-IL-8 antiserum. Anti-IL-1 beta and anti-IL-8 antiserum reduced the hCG-induced ovulation rate, but a synergistic effect was not evident when these antisera were injected simultaneously. Anti-IL-1 receptor antagonist antiserum had no apparent effect on ovulatory efficiency.Conclusion(s): IL-1 beta, IL-8, and IL-1 receptor antagonist may affect the accumulation of related cytokines in ovaries and may be involved in ovulation. (Fertil Steril(R) 1998;70:759-65. (C) 1998 by American Society for Reproductive Medicine.).

The objective of our study was to elucidate the involvement of interleukin (IL)-8 in the hCG-induced rabbit ovulatory process. After administering hCG (100 IU i.v.), we examined myeloperoxidase (MPO) activity, which represents neutrophil accumulation; neutrophil elastase (NE) activity, which is an indicator of neutrophil activity; and levels of IL-8 in the ovaries. The maximal level of IL-8 was observed before MPO and NE activities reached a peak: production of IL-8, MPO, and NE activities peaked, respectively, at 4 h (5.58 +/- 0.88 pg/mg ovary, n = 13), 6 h (1.07 +/- 0.13 deltaA/min per gram ovary, n = 8), and 9 h (18.89 +/- 1.05 U/g ovary, n = 8). Anti-rabbit IL-8 antiserum given i.v. significantly reduced the maximal levels of hCG-induced MPO activity (antiserum vs. control; 0.34 +/- 0.04 vs. 1.12 +/- 0.11 deltaA/min per gram ovary, n = 14, p < 0.001) and NE activity (8.14 +/- 0.85 vs. 18.30 +/- 0.79 U/g ovary, n = 14, p < 0.001). The hCG-induced ovulation rate was significantly inhibited by the antiserum (50.5% vs. 83.9%, n = 14, p < 0.001). Intraperitoneal injection of 100 mg/kg of ONO-5046, a specific NE inhibitor, also attenuated the ovulation rate (ONO-5046 vs. vehicle; 56.0% vs. 74.0%, n = 14, p < 0.05). These findings clearly indicate that IL-8 has an important role in the hCG-induced ovulatory process through the accumulation and activation of neutrophils.

The objective of our study was to elucidate the involvement of interleukin (IL)-8 in the hCG-induced rabbit ovulatory process. After administering hCG (100 IU i.v.), we examined myeloperoxidase (MPO) activity, which represents neutrophil accumulation; neutrophil elastase (NE) activity, which is an indicator of neutrophil activity; and levels of IL-8 in the ovaries. The maximal level of IL-8 was observed before MPO and NE activities reached a peak: production of IL-8, MPO, and NE activities peaked, respectively, at 4 h (5.58 +/- 0.88 pg/mg ovary, n = 13), 6 h (1.07 +/- 0.13 deltaA/min per gram ovary, n = 8), and 9 h (18.89 +/- 1.05 U/g ovary, n = 8). Anti-rabbit IL-8 antiserum given i.v. significantly reduced the maximal levels of hCG-induced MPO activity (antiserum vs. control; 0.34 +/- 0.04 vs. 1.12 +/- 0.11 deltaA/min per gram ovary, n = 14, p < 0.001) and NE activity (8.14 +/- 0.85 vs. 18.30 +/- 0.79 U/g ovary, n = 14, p < 0.001). The hCG-induced ovulation rate was significantly inhibited by the antiserum (50.5% vs. 83.9%, n = 14, p < 0.001). Intraperitoneal injection of 100 mg/kg of ONO-5046, a specific NE inhibitor, also attenuated the ovulation rate (ONO-5046 vs. vehicle; 56.0% vs. 74.0%, n = 14, p < 0.05). These findings clearly indicate that IL-8 has an important role in the hCG-induced ovulatory process through the accumulation and activation of neutrophils.

The purpose of the present study was to investigate a possible participation of the kinin-kallikrein system (KKS) in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Symptoms of hyperstimulation were produced in immature female rats using equine chorionic gonadotrophin followed by human chorionic gonadotrophin (HCG). At 48 h after the HCG injection, rats were injected s.c. with 100 microg/kg of HOE140, bradykinin-2 receptor antagonist. Capillary permeability was evaluated using peritoneal Evans blue dye (EB) concentrations 30 min after the i.v. injections. The EB concentrations in the hyperstimulated rats were significantly reduced 4 and 6 h after the HOE140 injection, compared with those injected with the vehicle as a control (4.58+/-0.80 versus 8.22+/-0.87 and 4.32+/-0.74 versus 8.35+/-1.03 microg respectively; P < 0.03), indicating the involvement of kinin in the pathophysiology of OHSS in this model. The administration of 10 IU aprotinin significantly reduced the peritoneal EB concentration when compared with the control (4.13+/-0.53 versus 7.95+/-1.06 microg; P < 0.01), implicating a possible role of kallikrein. Furthermore, pretreatment with RU486 (5 or 10 mg/kg) resulted in a significant reduction of ovarian kinin concentrations 48 h after the HCG injection, compared with the control (1.22+/-0.07 or 1.43+/-0.07 versus 1.94+/-0.10 pg/mg; P < 0.005 and P < 0.05 respectively). Similar results were obtained in the peritoneal EB concentrations. In addition, a significant correlation between the ovarian kinin and peritoneal EB concentrations was observed (P < 0.001, r = 0.539). Thus it was suggested that ovarian KKS plays an intermediary role in the progesterone-induced augmentation of capillary permeability in this experimental model, indicating the involvement of KKS in the pathophysiology of OHSS.

We present a case of well differentiated endometrioid adenocarcinoma of the endometrium in a 29-year-old woman, developing 6 months after an atypical polypoid adenomyoma (APA) was diagnosed by curettage. Four cases of APA with coexistent endometrial adenocarcinoma were recently reported. To our knowledge, this is the first reported case of endometrioid adenocarcinoma following conservative treatment for an APA. Since APA may be associated with the development of adenocarcinoma, careful follow-up with hysteroscopy and endometrial sampling is recommended in a woman with APA who desires continued fertility.

The role of progesterone in capillary permeability, which may be causally related to the pathophysiology of ovarian hyperstimulation syndrome (OHSS), was investigated in immature rats. A total of 96 female Wistar rats aged 22 days were given 10 IU of equine chorionic gonadotrophin daily for 4 consecutive days, and given 30 IU of human chorionic gonadotrophin on the fifth day to produce hyperstimulated manifestations. On the sixth day, groups of 12 rats each received RU486 at a dose of 0, 1, 2.5, 5, 10, 15 or 20 mg/kg (groups 1-7), or RU486 at 5 mg/kg combined with 6alpha-methyl-17alpha-hydroxy-progesterone acetate at 10 mg/kg (group 8). On the 7th day, the ovarian weight and capillary permeability of all rats were determined. Capillary permeability was evaluated from the Evans blue dye (EB) content in the ovaries and the EB level in peritoneal irrigated fluid at 30 min after the intravenous injection of EB. The peritoneal fluid EB level was significantly lower in groups 3, 4, and 5 than in the vehicle group. However, the peritoneal EB level in group 7 was higher than in the vehicle group, although not significantly. These findings demonstrated that RU486 has two divergent effects on capillary permeability, depending on the dose administered. In group 8, on the other hand, the peritoneal EB level and ovarian EB content were significantly higher than the corresponding values in group 4, respectively, suggesting that progesterone has a role in capillary permeability and ovarian enlargement. These results imply that progesterone may contribute, at least in part, to the pathophysiology of OHSS in this experimental model.

The fine structure of the macrophages involved in the human female reproductive organs are described. Macrophages appear inside and outside of developing follicles in addition to atretic follicles and regressing corpora lutea. No vacuoles or granules are found in their cytoplasm, and there is direct contact between macrophages and adjacent granulosa cells. Peritoneal macrophages are classified into four types according to their ultracytochemical localization of endogenous peroxidase activity. Under stimulated conditions, the number of exudate macrophages is increased. Macrophages are present in the endosalpingeal stroma and smooth muscle layer of the Fallopian. tubes. Their number increases during menstruation and from the early until the mid-secretory phase. Menstrual-phase macrophages in the endosalpingeal stroma show characteristic phagocytic vacuoles and granules in the cytoplasm. In the secretory phase, macrophages possess well-developed intracytoplasmic organelles with fewer cytoplasmic vacuoles and granules. Decidual tissue in the placenta is composed of cells such as macrophages, lymphocytes, fibroblasts, and stromal cells. Very close contact is frequently observed between. macrophages and decidual cells. Macrophages in the chorionic villi are characterized by numerous vacuoles of varying size and the presence of small granules scattered in the cytoplasm. The hCG-beta subunit is localized in coated pits and vesicles, as well as in the vacuoles and granules. Macrophages constitute an extremely heterogeneous population of cells in, the reproductive organs of the female. Such heterogeneity may result from differences in their specific tissues function.