Search

Objective: To investigate the expression of moesin, p21-activated kinase 4 (PAK 4), matrix metalloproteinases (MMP 2, MMP 9), and CD34 in the eutopic and ectopic endometrium in different forms of adenomyosis., Material and Methods: Fifty uteri removed for diffuse adenomyosis and for adenomyomas were examined in reproductive-aged (n=25) and premenopausal (n=25) women. A comparison group included 20 uteri removed for intramural and subserosal fibroids in reproductive-aged and premenopausal women. The investigators performed histological and immunohistochemical (using antibodies to moesin, PAK 4, MMP 2, MMP 9, and CD34) examinations of the eutopic and ectopic endometrium., Results: Different forms of adenomyosis were characterized by the irregular border of the endometrium and myometrium due to that there were multiple foci of ingrowth of the basal layer of the endometrium through the terminal plate into the myometrium. In both diffuse adenomyosis and adenomyomas, the basal layer of the eutopic and ectopic endometrium differed many (3-8.5) times, showing the higher expression of the enzymes in the epithelial and stromal cells, which affected their invasive activity (moesin, PAK 4, MMP 2 and MMP 9), and the increased number of CD34 cells in its stroma. At the same time, there were no statistically significant differences in their expression in the basal layer of the eutopic and ectopic endometrium in diffuse adenomyosis and adenomyomas., Conclusion: The findings favor the theory of the pathogenesis of adenomyosis due to the invasion of the eutopic endometrium into the myometrium.

Endometriosis is a dyshormonal immune-dependent genetically determined disease, which appears as an endometrioid tissue that grows outside the uterine. Endometriosis is one of the most urgent problems of medicine. To date, new concepts of the endometriosis etiology and pathogenesis have been developed, but, despite their abundance, there is no unified theory. Genetic and epigenetic factors result in changes in an expression of aromatase, steroidogenic factor 1, and estrogen receptors are suggested to be the main cause of endometriosis. These changes lead to an active synthesis of various pro-inflammatory agents and a nerve growth factor, that are important in the development of pain syndrome. Also, changes in the progesterone receptor functioning and the local progesterone resistance development decrease the antiproliferative activity, apoptosis, and the anti-inflammatory substances level, as well as increase the prostaglandin, metalloproteinase activity, and level of hypoxia factors. In addition, there are shreds of evidence that endometriosis is associated with the risk of malignant tumors development, so new concepts for understanding these mechanisms are actively developing. Some of these mechanisms are discussed in this review.

The article covers the management of patients with internal genital endometriosis, in which the polymorphism of the glutathione-S-transferase genes has been diagnosed. The aim of our study was to select the optimal conservative method for treatment of internal genital endometriosis in women of reproductive age by developing complex therapy taking into account the polymorphism of the genes of the detoxification system. 102 patients with combined gynecological pathology were examined. All patients were subject to a dynamic clinical and laboratory examination. According to the presence of GSTT1 genes deletion, GSTM1 has established research groups and treatment. Analyzing the performed research, it was discovered that the clinical efficacy of complex treatment depended on the genotypes of patients. The presence of pathologically burdened alleles of genes GSTM1 and GSTT1 somewhat reduced the response to standard treatment in the second group of patients. However, when comparing the levels achieved in the group I of patients, it was determined that in general, the clinical effect of our proposed therapy was more pronounced than in the II and III clinical groups. Clinical research has proved the effectiveness of hormone therapy combined with immunomodulatory and target drug in the form of reducing recurrence and restoring fertility.

Unlabelled: Endometriosis (EM) is morphologically characterized by the development of extrauterine endometrioid heterotopies, the major clinical symptoms of which is chronic pelvic pain, which is a serious problem not only in modern gynecology, but also in public health as a whole., Aim: to investigate neurogenic markers in the foci of EM of various sites and histological structure in women with and without pain syndrome., Material and Methods: The investigation was performed using the operative material (resected segments of the intestine, bladder, rectovaginal septum, and small pelvic peritoneum) obtained from 52 women with an intraoperative and morphologically verified diagnosis of EM and (Group 1) and without (Group 2) pain syndrome. Immunohistochemical examination was made on paraffin-embedded tissue sections in accordance with the standard protocols, by using the antibodies: 1) anti-PGP 9.5 polyclonal rabbit antibodies; 2) mouse anti-human neurofilament (NF) protein monoclonal antibodies (Clone 2F1); 3) mouse anti-nerve growth factor (NGF) monoclonal antibodies; 4) monoclonal mouse anti-human NGF receptor p75 (NGFRp75) antibodies (Dako, Denmark)., Results: Our findings demonstrate differences in the expression of PGP 9.5, NFs, NGF, and NGFRp75 in the foci and adjacent tissue in painful and painless EM irrespective of the locations of heterotopies., Conclusion: The found molecular features are a manifestation of the remodeling of nerve fibers and nerve endings in the foci of EM and PGP9.5, NGF, and NGFRp75 give rise to nerve fiber neoformation and pain syndrome in EM. At the same time, the immunohistochemical phenotype of EM foci does not depend on their site and reflects the presence or absence of pain syndrome.

Exogenous dinitrosyl iron complexes (DNIC) with thiol-containing ligands as NO and NO+ donors are capable of exerting both regulatory and cytotoxic effects on diverse biological processes similarly to those characteristic of endogenous nitric oxide. Regulatory activity of DNIC (vasodilation, hypotension, trombosis suppression, red blood cell elasticity increasing, skin wound healing acceleration, penile erection inducing, etc) is determined by their capacity of NO and NO+ transfer to biological targets of the latter (hemo- and thiol-containing proteins, respectively) due to higher affinity of the proteins for NO and NO+ than that of DNIC. Cytotoxic activity of DNIC is endowed with rapid DNIC decomposition under action of iron-chelating compounds resulting in appearance of NO and NO+ in cells and tissues in high amount. The latter mechanism is suggested to cause the blocking effect of DNIC as cytotoxic effectors on the development of benign endometrial tumors in rats with experimental endometriosis. It is also proposed that. a similar mechanism can operate causing at least a delay of malignant tumor proliferation under action of DNIC.

The aim of this paper is to provide a systematic review of the role of the genetic factors, detoxication systems and oxidative stress in the pathogenesis of endometriosis and infertility. Endometriosis and infertility are still both the most uncommon diseases in gynecology. Many aspects of female reproductive function are strongly influenced by genetic factors, and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as polycystic ovary syndrome, endometriosis, fibroids, cancer (ovarian, vulvar, cervical), premature ovarian failure, recurrent pregnancy loss and pre-eclampsia. The most solid evidence linking specific polymorphisms to endometriosis is showed by the studies investigating a phase II detoxification enzyme. No data were found concerning influences of the genetic factors on the female infertility. Contrary, a lot of studies devoted to the genetic factors of male infertility are presented. It's known that endometriosis associated with increased systemic oxidative stress. The implication of increased systemic oxidative stress in disease progression or the association with other oxidative stress-related pathologic conditions needs to be addressed in further studies. The majority of studies suggest a reduced antioxidant capacity in infertile wome with endometriosis. In the present review we discussed the role of the genetic factors in the pathogenesis of endometriosis and infertility. NAT2 polimorphism, xenobiotic methabolism and exogenous factors are somehow related with these diseases. An altered balance between pro-oxidant antioxidant activities may have an impact on folliculogenesis and adequate embryo development.

The investigation of leukocytic elastase (LE) and alpha1-proteinase inhibitor (alpha1-PI) from patients with different stage adenomyosis and in control group was found activation innate immunity system in all the patients with adenomyosis. The degree of LE activity is a prevalence rate of adenomyosis. The degree of alpha1-PI activity is correlated with antiproteolytic potential that blocks the effects shown by LE. It can lead the prognose of disease and timely treatment.

Adenomyosis, ovarian endometriosis and extragenital endometriosis are clinico-pathologic types of one nosologic form as endometrioid disease (ED). ED's clinical presentations are various, but they are essentially characterized by a pain syndrome and disorder of menstrual cycle. The comparative clinico-pathologic analysis of adenomyosis, ovarian endometriosis, and extragenital endometriosis affords to suppose that theirs clinical course, the intensity and character of symptoms, as well as morphogenetic processes are generally determined by the organ localization. Topography of foci, theirs organ localization, morphological and morphofunctional features vary within one type of ED and even within one organ. So the separation of various ED's morphofunctional forms, its clinico-phatological features and intensity of its morphofunctional activity is necessary. All forms of ED have general morphogenesis features including the various form of proliferation, secretion, regression, wave-like courses of dishormonal morphogenetic manifestation within one organ. Typical for all ED's types pathologic synthesis of aromatase cytochrome P-450 promotes the local estrogens synthesis from androgens, transition of endometrioid heterotopias to the quite different level of existence and self-regulation contributing autonomous wave-like chronic ED' clinic course.

The molecular biological features of the eutopic and ectopic endometrium were studied in 46 patients with adenomyosis, 44 with endometrioid cysts in the ovaries, and 34 with disseminated mixed forms of genital endometriosis. Reproductive-aged patients with the eutopic endometrium in a proliferation phase with hyperplastic or inflammatory changes were selected. Ten samples of the endometrium in a phase proliferation, which had been obtained at medicolegal autopsy of women without reproductive disorders, were studied as a control group. Both the glandular and stromal components of the ectopic and eutopic endometrium in different forms of endometriosis were shown to differ from the intact endometrium in their molecular biological features (the expression of Ki-67, Bcl-2, Bax, vascular endothelial growth factor, transforming growth factor-beta1, matrix metalloproteinases 2 and 10, matrix metalloproteinase-2 inhibitor, the enzyme cytochrome P450 aromatase.

The purpose of the investigation was to study the morphological variants and molecular changes of the endothelial component of adenomyosis (AM) concurrent with endometrial adenocarcinoma (EAC). Monoclonal and polyclonal antibodies to ApoCas, Cl 2, 3, and 5, Ki-7, MMP-2, MMP-9, TIMP-1, E-cadherin, COX-2, EGFR, and VEGF were used as primary antibodies. The AM foci displayed the following types of epithelial changes: the epithelium corresponding to the proliferation stage; epithelial hyperplasia with and without atypia; atrophic epithelium. There was an increased expression of ApoCas, Ki-67, MMP-2, MMP-9, COX-2, VEGF, and EGFR, which increased from proliferation to hyperplasia with atypia. The maximum expression of the markers was seen in EAC. The foci of AM, which corresponded to epithelial hyperplasia with atypia, were characterized by the oncomarker changes supporting its malignant potential: elevated Ki-67 and EGRF, reduced E-cadherin, changes in MMP-2, MMP-9, TIMP-1, and claudins-2, -3, and -5.

The expression of E-cadherin and beta-catenin in the eutopic and ectopic endometrium was studied in 40 patients with adenomyosis and 12 without this condition, by using an immunohistochemical test and enzyme immunoassay. There was increased expression of E-cadherin and beta-catenin in the eutopic and ectopic endometrium in adenomyosis. The cytoplasmic expression of beta-catenin was also revealed in the smooth muscle cells surrounding the foci of adenomyosis. The E-cadherin concentration measured by enzyme immunoassay was significantly higher in the endometrium and myometrium of patients with adenomyosis than in the controls. There was a higher expression of this protein with a longer duration of the disease. Thus, the formation of ectopic foci in adenomyosis may be argued to be unassociated with the decreased adhesion of epithelial cells. On the contrary, the authors documented the enhanced adhesion of epithelial cells in the ectopic foci, which was likely to be adaptive due to the altered microcirculation.

The purpose of the study was to reveal clinical and morphological parallels and to define molecular mechanisms, the regulation of proliferation, apoptosis, neoangiogenesis, and the extent of abnormal tissue in adenomyosis (AM). The surgical material obtained from 492 patients of late reproductive age was examined. The data of clinico-anamnestic and instrumental diagnostic studies and a morphological study with hematoxylin and eosin staining were analyzed. An immunohistochemical study was carried out on serial paraffin sections (n = 115), by applying antibodies to Apo-CAS, Ki67, PCNA, CD-34, MMP-1, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-3, TIMP-4, and E-cadherin. The specific features of their morphological structure and the clinical course of the disease allowed identification of its active and inactive forms. Immunohistochemically active AM is characterized by high proliferation, diminished apoptosis, and increased expression of MMPs along with lower expression of TIMPs by glandular and stromal cells as compared with inactive AM. At the same time, there was a high activity of stromal cells in the foci of active AM. The results of the study may be used to predict the course of the disease and to elaborate target therapy for AM.

A complex morphological and morphometric study was used to examine endometrial biopsy specimens from 133 patients with bacterial vaginosis (BV). Chronic endometritis (CE) was detected in 100% of them. The morphological components of CE in BV were significant dystrophic changes in integumentary endotheliocytes and glandular cells, differently pronounced polymorphocellular infiltration of the uterine mucosa with signs of tissue lymphopenia, as well as stromal and vascular fibroblastic changes with the decreased volume density of the endometrial integumentary endothelium, lower relative volumes of glands, and increased relative volume of connective tissue. The characteristic structural changes for CE and BV are intensive processes of apoptosis of the uterine mucosal epithelium in the presence of its slight proliferative activity, which determines progressive endometrial atrophy and may contribute to non-developing pregnancy. As this takes place, discrinism occurs in the uterine mucosa, mainly as inadequate progesterone reception of endometrial target cells, which leads to uterine gland dysfunction and may also cause fetal depletion syndrome.

The review of literature concerns some aspects of the pathogenesis of adenomyosis in terms of occurring molecular biological processes. It pools the literature data on endometrial capacity to be plunged into the deep myometrial layers--the expression of adhesive molecules, endometrial proteolytic activity, angiogenetic factors, and apoptosis-proliferation relationships. Evidence for the metaplastic theory of the disease is also presented. Emphasis is laid on the characteristics of a subendometrial zone whose pathology plays an important role in adenomyosis.

One hundred and fifty-three women with external genital endometriosis (EM), stages 1-4, and 30 healthy fertile women were examined. The peripheral-blood serum and daily urine were tested with the level of the mean weight molecules (MWM) being determined spectrophotometrically at lambda = 230-300 nm. The minimal MWM concentrations were detected in blood in cases of the stage-1 endometrioid process; they were significantly lower versus those observed in the healthy women at the maximal urine concentrations, i.e. well above the normal value. An increasing MWM blood content is registered in stages 2-4 EM, which exceeds the normal figure, whereas MWM was minimal in urine in stage 2, it was progressively increasing later but did not reach the value of stage 1. The external EM was associated with an enhanced MWM formation; it is noteworthy, that their concentrations in blood serum directly correlated with a stage of the endometrioid process. A reliably lower MWM level in stage 1 EM is below the normal value, while its maximal increase in urine could be regarded as a compensation-adaptation reaction aimed at removing the toxic substances from the body. A reduced MWM discharge with urine and its growth in blood plasma were observed in further progressing of the endometrioid process, which is preconditioned by the toxic impact of MWM exerted on the nephron.

The study of the effect of radon water in different concentrations (1.5 and 6.5 kBk/l) on a clinical status and endocrine system of patients with genital endometriosis has detected a positive action of both concentrations. High-concentration radon water more effectively decreased the size and tenderness of endometriotic foci as well as concentration of sex steroids. Therefore, a differential approach is needed to prescription of radon water. Its concentration must be based on endometriosis extension and severity of the process.

Our objective in this work was to study efficiency of cryohormonal treatment in patients with internal endometriosis. As many as 27 female patients were treated, in whom the diagnosis of internal endometriosis had been confirmed with the aid of ultrasound investigation, hysteroscopy and laparoscopy. All above patients underwent intrauterine cryodestruction of endometrioidal loci by a contact technique over 3 minutes with subsequent administration of dipherelin, 3.75 mg every 28 days, a total of 4 to 6 injections for the course. The study made has shown high efficacy of the employed treatment option.

A method of flow horizontal chromatography has been developed permitting investigation of blood and tissue cellular phospholipids ruling out lipid peroxidation effects on cellular membranes. Phospholipid levels of blood and myometrial tissue cells were measured by this method in 67 patients with histologically verified internal endometriosis. Phospholipid and phosphatidyl inosite levels in platelets and immunocompetent cells of these patients reliably differed from those in healthy women. Phosphatidyl inosite levels of heterotopic endometrial tissue was increased by 1.4 times vs. the norm on an average. In parallel with this, a reliable change of phosphatidyl cholines and inosites levels in endometriosis foci were detected as against their levels in intact tissue. The authors suggest a method for the diagnosis of internal endometriosis by phosphatidyl inosite levels in blood lymphocytes.

The authors analyze the data of ultrasonic examinations in 110 patients operated on for adenomyosis and in 50 patients with this condition not exposed to surgery, in whom the diagnosis was made after comprehensive examinations. The accuracy of ultrasonic diagnosis correlated with the disease severity. Diagnostic difficulties are explained by the absence of pathognomonic echographic criteria, frequent associations with myoma, and with false echo signals emerging in the myometrium. Transabdominal and transvaginal methods may be recommended for a more precise diagnosis; it is desirable to single out several echographic criteria and by all means correlate them to clinical data. An attempt at morphologic explanation of the principal echographic criteria of adenomyosis has been made. Echo-negative structures in the myometrium emerge mainly as a result of the signal reflection from the zone of perifocal membranogenic edema of myometrial stroma developing round endometriosis focus.

Eighty-six patients with histologically verified internal endometriosis were examined using histochemical, morphometric methods, and measurements of blood and myometrial tissue phosphatidyl inosites. Blood levels of phosphatidyl inosites were found reliably decreased in the patients vs. normal subjects, whereas their levels in myometrial tissue were significantly increased. Increased counts of tissue basophils, microcirculation disorders, lymphostasis and membranogenic stromal edema development were observed round endometriosis foci. Changes in the basic substance and fibrous structures of myometrial connective tissue complex were revealed, most marked in the areas adjacent to the endometrium. A possible mechanism of the development of pathologic shifts in internal endometriosis is discussed.

Levels of phospholipids, phosphoinosites, phosphatidylinosite-3-phosphates, diacylglycerols, arachidonic acid, prostaglandins E, F, J, and thromboxane A2 in patients with endometriosis and cancer of the corpus uteri were found to differ from those in healthy women. Biochemical parameters of whole blood and myometrial tissue of endometriosis patients differ significantly from those of patients with corpus uteri cancer. The authors suggest that reduction of phosphatidylinosite and phosphatidulinosite-3-phosphate levels in whole blood and their parallel increase in myometrial tissue are conducive to cellular proliferation and malignant degeneration.

The specific binding of an antiestrogen tamoxifen to receptors of estradiol of target cells plasmic membranes of the human endometrium was studied in some hyperplastic processes. The relative binding activity of tamoxifen was determined. Tamoxifen was found to compete with estradiol for binding to plasmic membranes of the endometrial cells.

Patients with ovarian endometriosis have been examined during the follicular and luteal phase of the ovulatory and the second phase of the anovulatory cycles. Estradiol and progesterone blood concentrations measured on operation days and during the respective ovulatory phases were in a normal range. Ovulation and endometrial hyperplasia reduced basal progesterone concentrations. Comparison of findings on steroid receptor systems in the endometrium and endometrioid ovarian cysts indicated that they were identical. The findings were different in ovulation and endometrial hyperplasia. These patterns provided criteria for endometrial response to female sex hormones by assaying endometrial intracellular steroid receptor systems in normally ovulating patients with ovarian endometriosis.