metallothionein and Endometriosis

 To characterize the patterns of cell differentiation, proliferation, and tissue invasion in eutopic and ectopic endometrium of rabbits with induced endometriotic lesions via a well- known experimental model, 4 and 8 weeks after the endometrial implantation procedure..  Twenty-nine female New Zealand rabbits underwent laparotomy for endometriosis induction through the resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of animals (one with 14 animals, and the other with15) were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised along with the opposite uterine horn for endometrial gland and stroma determination. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissues for analysis of the following markers: metalloprotease (MMP-9) and tissue inhibitor of metalloprotease (TIMP-2), which are involved in the invasive capacity of the endometrial tissue; and metallothionein (MT) and p63, which are involved in cell differentiation and proliferation..  The intensity of the immunostaining for MMP9, TIMP-2, MT, and p63 was higher in ectopic endometria than in eutopic endometria. However, when the ectopic lesions were compared at 4 and 8 weeks, no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue..  Ectopic endometrial lesions seem to express greater power for cell differentiation and tissue invasion, compared with eutopic endometria, demonstrating a potentially invasive, progressive, and heterogeneous presentation of endometriosis..  Caracterizar o padrão de diferenciação celular, proliferação e invasão tecidual em endométrio eutópico e ectópico de coelhas com lesões de endometriose induzidas por um modelo experimental 4 e 8 semanas após o procedimento de implantação endometrial. MéTODOS:  Vinte e nove coelhas fêmeas Nova Zelândia foram submetidas a laparotomia para indução de endometriose através da ressecção de um dos cornos uterinos, isolamento do endométrio e fixação do tecido no peritônio pélvico. Dois grupos de animais (14 animais em um grupo e 15 animais no outro) foram sacrificados 4 e 8 semanas após a indução da endometriose. A lesão foi excisada junto com o corno uterino contralateral para determinação da presença de glândulas e de estroma endometrial. Reações de imunohistoquímica foram realizadas no tecido endometrial eutópico e ectópico para análise dos seguintes marcadores: metaloprotease (MMP9) e inibidor tecidual da metaloprotease 2 (TIMP-2), os quais estão envolvidos na capacidade de invasão do tecido endometrial; e metalotioneina (MT) e p63, os quais estão envolvidos na diferenciação e proliferação celular..  A intensidade da imunomarcação para MMP9, TIMP-2, MT e p63 foi mais alta nos endométrios ectópicos do que nos endométrios eutópicos. Contudo, quando as lesões foram comparadas entre 4 e 8 semanas, nenhuma diferença foi observada, com exceção do marcador p63, o qual foi mais evidente depois de 8 semanas de evolução do tecido endometrial ectópico. CONCLUSãO:  Lesões endometriais ectópicas parecem expressar maior poder de diferenciação celular e de invasão tecidual comparadas com endométrios eutópicos, demonstrando o potencial de invasão, de progressão e de apresentação heterogênea da endometriose.

Topics: Animals; Cell Differentiation; Cell Proliferation; Choristoma; Disease Models, Animal; Endometriosis; Endometrium; Female; Matrix Metalloproteinase 9; Membrane Proteins; Metallothionein; Rabbits; Tissue Inhibitor of Metalloproteinase-2

The coexistence of endometrial and immune cells during decidualization is preserved by the ability of endometrial cells to regulate the cytotoxic immune activity and their capability to be resistant to immune-mediated apoptosis. These phenomena enable the survival of endometrial ectopic cells. RCAS1 is responsible for regulation of cytotoxic activity. Metallothionein expression seems to protect endometrial cells against apoptosis. The aim of the present study was to evaluate RCAS1 and metallothionein expression in human ovarian and scar endometriomas in relation to the presence of immune cells and their activity.. Metallothionein, RCAS1, CD25, CD69, CD56, CD16, CD68 antigen expression was assessed by immunohistochemistry in ovarian and scar endometriomas tissue samples which were obtained from 33 patients. The secretory endometrium was used as a control group (15 patients).. The lowest metallothionein expression was revealed in ovarian endometriomas in comparison to scar endometriomas and to the control group. RCAS1 expression was at the highest level in the secretory endometrium and it was at comparable levels in ovarian and scar endometriomas. Similarly, the number of CD56-positive cells was lower in scar and ovarian endometriomas than in the secretory endometrium. The highest number of macrophages was found in ovarian endometriomas. RCAS1-positive macrophages were observed only in ovarian endometriomas. CD25 and CD69 antigen expression was higher in scar and ovarian endometriomas than in the control group.. The expression of RCAS1 and metallothionein by endometrial cells may favor the persistence of these cells in ectopic localization both in scar following cesarean section and in ovarian endometriosis.

Topics: Abdominal Wall; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; CD56 Antigen; Cicatrix; Endometriosis; Female; Humans; Immunohistochemistry; Lectins, C-Type; Macrophages; Metallothionein; Ovarian Diseases; Ovary; Receptors, IgG; Receptors, Interleukin-2

Acquiring the immune-mediated apoptosis and the ability to regulate the cytotoxic immune response are the main phenomena playing fundamental roles in such situations as neoplasm survival and creation of immune tolerance during pregnancy. The aim of this study was to investigate these phenomena through the evaluation of metallothionein and RCAS1 proteins in neoplasm and its healthy environment (clear surgical margin), physiological conditions in placenta and its environment (decidua) and the comparison to non-neoplasmatic lesions originating from the environment (nasal polyps, endometriosis). We have shown that the growth of RCAS1 expression was simultaneous to the infiltration of activated immunological cells of tumor environment as well as decidua. The activity of immunological cells was in our study selectively suppressed. Metallothionein expression growth was also observed in healthy tumors stroma and in decidua probably in response to the growing cytotoxic activity and tumor spread. Alterations in RCAS1 and Metallothionein expression seem to be associated with local immune dysfunction in nasal polyps and endometriosis. In conclusion, the ability to compensate the growing cytotoxic immune response is physiologically observed in decidua, the lost of this ability in tumor environment might participate in the development of tumor spread.

Topics: Antigens, Neoplasm; Apoptosis; Decidua; Endometriosis; Female; Humans; Immune Tolerance; Immunity, Cellular; Lymphatic Metastasis; Menstrual Cycle; Metallothionein; Nasal Polyps; Neoplasms; Placenta

Endometrium is a specialized organ in which phenomena controlling the level of cell proliferation and apoptosis are marked. The aim of our study was to determine the presence of proteins involved in apoptosis and proliferation: RCAS1, MT and the number of CD56-positive cells and their activity to elucidate their possible role in the development of adenocarcinoma and endometriosis.. MT, RCAS1, CD56-positivity and CD69 expression were assessed in 55 tissue samples by Western blot and immunohistochemistry methods.. We found that endometrium during secretory menstrual cycle phase is characterized by significantly higher RCAS1 and higher MT expression than in proliferative phase. The number of CD56-positive cells and the CD69 antigen expression was significantly increased. Endometrial adenocarcinoma was characterized by significantly increased RCAS1 expression, while MT expression was comparable to the level found in the secretory phase. The number of CD56-positive cells was significantly decreased and their activity was comparable to the level found in the secretory phase. Endometriosis was accompanied by significantly lower RCAS1 and MT expressions, with lower number of CD-56 positive cells and lower expression of CD69 antigen in comparison to the secretory phase.. The ability of endometrium to determine cytotoxic activity (RCAS1 expression changes) and high protection against DNA damage (MT expression) with concomitant changes in the number of immune cells and their activity, observed in normal endometrium during the menstrual cycle phases seems to be fundamental for pathological features of endometrial adenocarcinoma and endometriosis.

Topics: Adenocarcinoma; Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; CD56 Antigen; DNA Damage; Endometrial Neoplasms; Endometriosis; Endometrium; Female; Humans; Immunochemistry; Lectins, C-Type; Menstrual Cycle; Metallothionein; Middle Aged

Endometriosis is an illness accompanied by invasion features, but malignant changes appear extremely seldom. Metallothionein (MT) is a protein and takes part in the detoxicating processes of the organism. MT is located, among others, in benign and malignant neoplasms in animals as well as humans, mainly in the S phase of cellular cycle, and that is why MT is considered to be both an index of cell proliferation and tumor progress.. 34 specimens from 21 women with ovary endometriosis (III degree according to AFS) have been examined. The specimens were obtained during surgery and they were histopathologically verified. The material was coloured by H + E and by van Gieson method, and MT was determined immunohistochemically. The measurement of the cells number containing MT was performed with measurement system Multi-Scan Base V8.08, with the microscope Axiophot, Zeiss Jena in so-called measurements areas, with the surface 18802 microns 2.. High MT capacity was found in the epithelial cells in the endometriosis focus. This high MT capacity may imply that there exists the proliferation process in the focuses of external endometriosis. Simultaneously, the lowest MT capacity was discovered in glandular ducts.. Proliferating epithelial cells contain the highest capacity of MT, which indicates increase of number of dividing cells particularly in the S phase of cellular cycle and that is why MT can be considered one of the markers of ovary endometriosis.

Topics: Biomarkers, Tumor; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Endometriosis; Female; Humans; Immunohistochemistry; Metallothionein; Ovarian Diseases