Ovarian Mesothelium Research Articles

An unusual case of primary peritoneal adenocarcinoma

Primary peritoneal adenocarcinoma is sporadic with few cases cited in pre-existing literature. This cancer arises from the peritoneal epithelium lining of the abdomen, which is derived from extra ovarian mesothelium. It generally carries a poor prognosis. The treatment strategies are similar to ovarian serous papillary carcinoma. Report an incidental finding of primary peritoneal adenocarcinoma in a 39-year-old female army personnel, currently undergoing her chemotherapy and thriving. Exploratory laparotomy was done given the incidental finding of a mass on the contrast-enhanced computed tomography scan (CT). The mass was attached to the greater omentum, however, did not invade the mucosa of the transverse colon. Given this, part of greater omentum was removed. The findings of the immunohistochemical studies of the tumour are described within this report. The diagnosis of a primary peritoneal adenocarcinoma, stage II was established as no other primary site were found upon further investigation. The patient was treated with chemotherapy (carboplatin/paclitaxel) which was planned for 6 cycles. Otherwise, the patient had an uneventful postoperative course, is underway her chemotherapy regime and is planned for interim CT study to assess chemotherapy response. To conclude, isolated solitary primary peritoneal adenocarcinoma without peritoneal carcinomatosis, gastrointestinal manifestations and ascites are rare. This case, however, demonstrates the importance of its diagnosis, accurate evaluation and management.

Unravelling the Ovarian Endometrioma Pathogenesis: “The Long and Winding Road” across the Various Theories

Controversy exists regarding the pathogenesis of endometriotic ovarian cysts. Different and complex theories have been proposed over the years since the description of chocolate cysts by Sampson in 1921. We have herein reviewed findings in support and against the most widely accepted theories. According to the theory of Hughesdson and Brosens, a prerequisite for endometrioma formation seems to be the inversion and progressive invagination of the ovarian cortex after the accumulation of menstrual debris derived from bleeding of superficial endometriotic implants, which are located on the ovarian surface and adherent to the peritoneum. Disproving the metaplasia hypothesis put forward by Donnez and coworkers and supporting the involvement of the ovulation process in the development of ovarian endometriosis, Vercellini and colleagues have recently demonstrated that a cystic corpus luteum may be a transitory step toward endometrioma formation. As these theories are not able to explain the various aspects of endometrioma formation fully, the possibility that the coelomic metaplasia of the ovarian mesothelium with changes into typical endometrial glands and stroma might be responsible for the endometrioma formation cannot be totally ruled out. Further research is needed to clearly elucidate the pathogenetic aspects of endometriotic ovarian cysts.

Endometriosis and infertility

Endometriosis is frequent in infertile women, but the relation between these two conditions has still remained unclear. Our intention was to present the pathogenesis of endometriosis, mechanism of the associated infertility and a rational approach to treatment of this frequent medical problem. The peritoneal form is most probably generated by implantation of the endometrium by menstrual reflux. Endometriomas are most probably formed by invagination and metaplasia of the ovarian mesothelium or by metaplasia of the epithelium of inclusion cysts. Adenomyosis of the rectovaginal septum develops from embryonic remnants of the Mullerian ducts. Laparoscopy is a method of choice which provides safe diagnosis, estimation of the disease and is an optimal method of treatment. The relation between mild forms of disease (Stage I and II) and infertility has remained unclear. Surgical removal of ectopic foci does not affect female fertility. The expectant treatment during one to four years has been followed by pregnancy in 50% of patients. In patients with III and IV stage disease, there is a frequent mechanical cause of infertility. Expectant treatment was followed by 25% incidence of pregnancy in patients with stage III disease and 0% in patients with stage IV endometriosis. Surgical reconstruction of normal anatomical relations resulted in pregnancy in 40-60% of patients. Administration of any drug therapy, either single or combined with surgical treatment does not increase the fertility rate. Methods of assisted reproduction are alternative approaches to treatment and they have to be administered after unsuccessful surgical treatment. Pretreatment with GnRH agonists increases the efficacy of in vitro fertilization.

Influence of Growth Factors on Proliferation and Morphogenesis of Rabbit Ovarian Mesothelial Cells in Vitro1

The ovarian mesothelium (OM) is the source of one of the most frequent and lethal types of common ovarian epithelial tumors, the so-called papillary serous carcinomas. Recent work from our laboratory indicates the existence of postovulatory luteal OM mitogens with variable affinity for heparin. To further investigate the paracrine regulation of this ovarian tissue, rabbit ovarian mesothelial cells (OMC) were cultured in serum-free, fibronectin-rich HL-1 medium with or without one of the following luteal growth factors (0.1, 1, and 10 ng/ml): basic (bFGF) and acidic (aFGF) fibroblastic growth factors, epidermal growth factor (EGF), transforming growth factors alpha (TGF alpha) and beta (TGF beta), tumor necrosis factor alpha, platelet-derived growth factor (PDGF-BB), and vascular endothelial growth factor. After 8 days of culture, OMC growth was stimulated 3-fold by all tested doses of bFGF, EGF, and TGF alpha and 2-2.5-fold by 10 ng/ml of PDGF-BB and aFGF; it was inhibited more than 60% by TGF beta (10 ng/ml). In addition to enhancing the formation of cohesive OMC monolayers, most factors enhanced 3- to 6-fold the aggregation of OMC into papillary processes. The finding of a growth and morphogenetic response to intraluteal growth factors is novel and suggests a role for postovulatory paracrine regulation of OM pathobiology.

Ovarian mesothelial and extramesothelial cells in interactive culture.

The ovarian mesothelium (OM) represents the tissue of origin of ovarian epithelial cancer. To gain insight into the regulation of this tissue, OM organoids and submesothelial ovarian stromal cells (SC) were isolated from New Zealand White rabbits by a stepwise tissue dispersal technique, while granulosa cells (GC) were aspirated from mature follicles (14 +/- 4 groups/animal). OM and SC dispersal were sequentially accomplished by: a) 1-h incubation in collagenase type I (300 U/ml), gentle scraping of the ovarian surface, and 1 g sedimentation of OM organoids (equivalent to 0.93 +/- 0.40 x 10(6) cells/animal) on 5% bovine serum albumin (BSA); b) 2-h incubation in pronase-collagenase (0.5%-300 U/ml) under periodical resuspension and gentle scraping of SC (1.40 +/- 0.25 x 10(6)/animal) from OM-denuded ovaries. After a week-long in vitro expansion, OM cells (OMC) were cultured alone and with SC or GC within monocameral vessels or bicameral transfilter vessels in serumless, fibronectinrich (4 micrograms/ml) HL-1 medium. After 7 d of contact cell-cell interaction, cytokeratin-positive OMC became surrounded by fibroblastoid, vimentin-positive SC or by cytokeratin and vimentin-weakly positive GC. Filter-bound OMC humorally interacting with underlying SC or GC displayed a biphasic, epithelioid and spindle, morphology with universal cytokeratin expression. Bromo-2'-deoxyuridine (BrdU) immunoperoxidase revealed mean cell proliferation indices of 14.88% for OMC cultured alone, 11.21% and 19.39% for OMC cultured with GC or SC in monocameral dishes, and 15.25% or 22.47% for OMC cultured in bicameral vessels over GC or SC, respectively. This model provides an experimental tool for investigating the unexplored role of stromal-mesothelial interaction in OM pathobiology.

Reciprocal Interactions between Human Ovarian Surface Epithelial Cells and Adjacent Extracellular Matrix

The human ovarian surface epithelium (OSE), or ovarian mesothelium, is functionally complex as seen by its capacity to proliferate, migrate, and contribute to ovulation and ovulatory repair in response to cyclic hormonal and environmental changes. We wished to determine whether this phenotypic versatility is reflected in cell-extracellular matrix interactions in primary and low-passage culture. Comparisons of cultures maintained on different substrata revealed that these cells form cohesive monolayers on plastic, while fibrin clots enhance cell dispersion, and thus may provide a migratory cue. The cells invaded Matrigel as multicellular aggregates, while collagen gels mediated a morphologic epithelial-mesenchymal conversion. On plastic, the cells produced extracellular matrix components characteristic of epithelial basement membrane (laminin and collagen type IV), as well as stroma (collagen types I and III). In addition, ovarian surface epithelial cells secreted serine proteases and matrix metalloproteinases. The levels of chymotrypsin- and elastase-like proteases were dictated by the substratum: low levels were secreted by cells grown on plastic, intermediate levels on collagen gels and fibrin clots, and most protease was produced on Matrigel. The rate of cell proliferation varied with the substrata and was inversely related to protease secretion. Integrin expression was greatest on plastic and least on collagen gels where integrins were downregulated with time. α6/β4 was absent from all cells while varying levels of α2, α3, α5, β1, and vitronectin receptor were detected depending on the culture substratum employed. In low-passage cultures of human ovarian surface epithelial cells, then, cell shape, growth, protease production, and integrin expression are modulated by the extracellular matrix. The cells, in turn, alter extracellular matrix by synthesis, lysis, and physical remodeling, and express both stromal and epithelial characteristics. The broad repertoire of these functions may be related to their mesodermal origin, and may reflect the expression of a dual, epithelio-mesenchymal phenotype by relatively immature, uncommitted cells. The results demonstrate the great complexity and versatility of these interactions which render OSE cells capable of participating in numerous physiological and pathological processes.

Endothelial mitosis during the initial stages of corpus luteum neovascularization in the cycling adult rat.

The initial stages of neovascularization of the corpus luteum were studied in cycling adult rats using light-microscopic autoradiography. The aim of this analysis was to determine whether endothelial mitosis is a factor in this vascular growth and whether there are differences in the amount of mitotic activity in various regions of the ovary. Ovaries were examined at two time intervals: 1-2 hr and 7-8 hr following ovulation. Animals received an intraperitoneal injection of tritiated-thymidine 20 min prior to perfusion fixation of the ovaries. Autoradiographic demonstration of tritiated-thymidine labeling in endothelial nuclei was considered an indication of DNA synthesis preceding mitosis. The percentage of labeled endothelial cells in the ovaries at both time intervals varied according to the region of tissue examined and the stage of differentiation of that region. Stromal vessels were less heavily labeled than thecal vessels. Thecal vessels surrounding growing follicles were more heavily labeled than those surrounding atretic follicles. The heaviest labeling was seen in the developing corpora lutea 7-8 hr following ovulation. Minimal labeling was evident in the corpora lutea which were formed in previous cycles. A regional difference was also detected in the ovarian mesothelium. The portion of the mesothelium overlying ovulated follicles and developing corpora lutea had the greatest percentage of labeled cells. The major findings of this study were: endothelial mitosis was elevated in the initial stages of luteal neovascularization; the heightened endothelial labeling was confined to specific regions of the ovary; and mesothelium in close proximity to the developing corpora lutea also displayed heightened DNA synthesis.