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  1. Home
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Browsing by Subject "Endometrium"

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    3D model of the maternal-fetal interface: challenges, recent advances and beyond
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Passaponti, Sofia; Luongo, Francesca Paola; Ietta, Francesca; Luddi, Alice; Piombon, Paola
    Embryo implantation is a complex and highly coordinated process that involves an intricate network of factors establishing intimate contact at the maternal-fetal interface. Knowledge of the human implantation process is compromised by both ethical issues, which do not allow the study of this process in vivo, and by the accuracy and reproducibility of in vitro models of human endometrium. Effective and reliable embryo implantation models are, therefore, necessary to mimic the molecular event cascade that occurs in vivo. 3D models are considered a new step to foster precision medicine and an advanced tool for the study of endometrial biology, endometrium associated diseases and to understand the complex mechanisms surrounding endometrium-embryo crosstalk. In this review we explore the various methods by which 3D cultures of endometrium and trophoblast can be created, exploring targets and applications of these in vitro models.
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    Blind aspiration biopsy versus a guided hysteroscopic technique for investigation of the endometrium in infertile women
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Ejzenberg, Dani; de Jesus Simões, Manuel; Pinheiro, Walter; Soares Júnior, José Maria; Serafini, Paulo Cesar; Chada Baracat, Edmund
    Embryo implantation failure and recurrent abortion are common indications for endometrial evaluation to determine the implantation window and diagnose endometrial anomalies. There are few research studies comparing the efficacy of different techniques used for endometrial sampling in infertile females during the luteal phase. Likewise, morphometric studies of the endometrium through aspiration biopsy are scant. A cross-sectional study of 30 infertile and 10 fertile females was carried out. The study participants underwent hysteroscopic and aspiration biopsies (pipelle) at the midluteal phase. Computer-assisted morphometric and pathological anatomy analyses were conducted independently by two pathologists blinded to the study. The two endometrial sampling biopsy techniques were compared through morphometric and pathological anatomy analyses using three parameters: a) the amount of material collected for the endometrial studies; b) the scope and origin of sampled materials; and c) the quality of the sample. Both biopsy techniques produced sufficient material for analysis. The directed biopsies yielded higher quality samples from targeted segments of the uterine cavity because samples were homogeneous and had no architectural distortion (p<0.05). Blood was present only in the samples obtained through a Pipelle. Endometritis was detected in 10% of the infertile women. Our findings suggest that hysteroscopic biopsies are superior to blinded aspiration biopsies
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    Decidualized and pre-decidualized normal endometrial stromal cells produce more O-linked N-acetylglucosamine containing epitope H than non-decidualized normal endometrial stromal cells
    (Murcia : F. Hernández, 2006) Polyzos, P.T.; Arvanitis, L.; Charchanti, A.; Galani, V.; Havaki, S.; Kallioras, V.; Nakou, María; Faros, E.G.; Marinos, E.; Sgantzos, M.; Kittas, C.
    The epitope H contains an O-linked Nacetylglucosamine residue in a specific conformation and/or environment recognized by the monoclonal antibody H (mAbH). mAbH stains two bands with Mr x10-3 of 209 and 62 in lysates of cultured rat astrocytes. In addition, in extracts of cultured MCF-7 breast carcinoma cell line cells it stains cytokeratin 8 and five polypeptides originating from Triton X-100-soluble (Mr x10-3 of 232, 67 and 37) and from the Triton X-100- insoluble (Mr x10-3 of 51 and 50) fractions, respectively. In our previous studies we used the mAbH to investigate by immunostaining the expression of the epitope H in normal human brains, human brains with a variety of lesions, astrocytic tumors, infiltrating ductal breast carcinomas, fibroadenomas, and mitochondria-rich normal, metaplastic and neoplastic cells. In order to gain further insight into the expression patterns of the epitope H in human tissues we used the mAbH to investigate the immunohistochemical expression of the epitope H in normal human endometrium, including 30 cases of proliferative endometrium, 30 cases of early secretory endometrium, 30 cases of mid secretory endometrium, 30 cases of late secretory endometrium and 30 cases of decidual tissues. The main results were the following: 1) The decidual stromal cells presented in all cases high cytoplasmic expression of the epitope H; 2) The predecidual stromal cells presented in all cases of late secretory endometrium significant cytoplasmic expression of the epitope H ranging from moderate to high expression; 3) The non pre-decidual stromal cells of the functional endometrial layer presented in all cases insignificant cytoplasmic expression of the epitope H ranging from null to low expression; 4) The stromal cells of the basal layer of the endometrium and decidua did not express the epitope H in any case; 5) The endometrial stromal granulocytes did not express the epitope H in any case and 6) The blood vessel wall cells (endothelial and smooth muscle) of the endometrium through the whole duration of the menstrual cycle and of the decidua presented high cytoplasmic expression of the epitope H. It is concluded that decidualized and predecidualized human normal endometrial stromal cells show increased expression of the O-linked Nacetylglucosamine containing epitope H compared to non-decidualized endometrial stromal cells. These findings suggest that the expression of the epitope H may be under positive progesteronic control in normal human endometrium. Further investigation of the antigens bearing the epitope H might help to gain further insight into the histophysiology and the pathology of human endometrium.
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    Effects of low dose of tibolone on steroid receptors and Bcl-2 on the postmenopausal endometrium
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Reis, Benedito Fabiano; Lima, Sonia Maria Rolim R.; Silva, Gustavo Maximiliano D.; Francisco, Antonio Marcos C.; Barbosa, Lyliana Coutinho R.; Archangelo, Silvania C. Vieira; Grande, Rogerio M.
    Objective: A prospective randomized controlled trial was conducted to evaluate the effect of low dose of tibolone on the histology, expression of estrogen (ER) and progesterone receptors (PR) and Bcl2 protein, in endometrium of postmenopausal women. Method: Forty postmenopausal women consented to treatment and were allocated into two groups of 20 women: Group 1 (Control) without hormone replacement therapy (HRT); Group 2 (Tibolone) treatment at the dose of 1.25 mg/day of oral tibolone administered for a 24-week period. The effect on the endometrium was assessed by histology and the apoptosis marker Bcl-2. The immunoexpression of ER and PR were also measured. Results: Tibolone group showed higher expression of ER, PR and Bcl-2 protein in glandular epithelium and stroma compared to control group. Conclusion: Tibolone in a daily dose of 1.25 mg during 24 weeks demonstrated endometrial action that resulted in low proliferation and was shown to lead to atrophic endometrium. It had favorable effects on the postmenopausal endometrium due to its higher immunoexpression of PR and Bcl-2 protein in endometrial glandular epithelium, thereby creating a balance between pro-apoptotic and anti-apoptotic actions.
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    Expression of a putative stem cell marker Musashi-1 in endometrium
    (F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Lu, Xiaoye; Lin, Fangfang; Fang, Huijuan; Yang, Xuesong; Qin, Li
    Aim: Firstly to examine the expression characteristics of Musashi (Msi)-1 in fetal endometrium, reproductive normal endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, next, to focus on exploring the possibility that Msi-1 serves as a marker of the endometrial stem cells in-situ. Methods: Immunohistochemical staining was performed to detect the expression of Msi-1 in 20 cases of fetal endometrium, 20 cases of normal endometrium, 20 cases of endometrial hyperplasia and 50 cases of endometrioid adenocarcinoma respectively. Results: In fetal endometrium, Msi-1 positive cells were observed from the 12th week in epithelium, but the number of Msi-1 positive cells decreased with an increase in gestational age. In reproductive normal endometrium, Msi-1 expression presented as dispersed single cell and cell groups in the stroma adjacent to the myometrium. In endometrial hyperplasia and endometrioid adenocarcinoma, Msi-1 expression significantly increased and was more widely distributed. Conclusions: Msi-1 positive cells mainly lie in the stroma of normal endometrium, and the distribution pattern is consistent with that of the speculated endometrial stem cells. The high expression of Msi-1 in fetal endometrium and endometrioid adenocarcinoma suggests that Msi-1 positive cells have several characteristics of stem cells, such as high proliferative potentiality and multipotency. Considering these factors, this makes Msi-1 potentially a promising stem cell marker.
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    Expression of NA-1 symporter NIS in endometrial mucosa of fertile, sterile and post-menopausal women
    (Murcia : F. Hernández, 2008) Trovato, María; Vitarelli, Enrica; Tripepi, María; Abate, Antonino; Rizzo, Piero; Benedetto, Vincenzo; Sciacchitano, Salvatore; Grosso, Maddalena; Barresi, G.
    The expression of the Na/I Symporter (NIS) in the basolateral cell membrane of the thyroid follicular cells is responsible for the active accumulation of iodide within the thyroid gland and for the subsequent biosynthesis of thyroid hormones. However, several tissues, such as salivary glands, breast, stomach, colon, ovary and endometrium, express NIS even if they are unable to organify iodide. In order to investigate a possible role of NIS in the endometrium, we analyzed, by immunochemistry, the expression of NIS in 44 endometrial samples of 20 patients with primary unexplained infertility, 14 fertile women and 10 in postmenopausal. NIS immunostaining was detected in endometrial cells belonging to the majority of sterile, postmenopausal and fertile women. However, the sterile and post-menopausal patients showed a higher percentage of NIS reactive cells compared to the fertile women (60±21% and 57±18% vs 19±9%; p=0.0001). NIS immunostaining was localized on the membrane and cytoplasm of the endometrial cells. We could not find any correlation between endometrial thickness and NIS immunoexpression. Our results indicate that, in the absence of histological markers, a sterile endometrium can be recognized because of the high expressions of NIS. Moreover, NIS expressions, elevated in both sterile and menopause women, is not related to the estrogen levels, but it could be modulated by factors common to the two conditions. In conclusion, we speculate that NIS may play a role in the development of female sterility.
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    Expression of toll-like receptors in the human decidua
    (Murcia : F. Hernández, 2007) Krikun, G.; Lockwood, C.J.; Abrahams, V.M.; Mor, G.; Paidas, M.; Guller, S.
    Background: Successful trophoblast invasion and transformation of the maternal spiral arteries requires that the pregnant endometrium (i.e., decidua) act in an immunologically paradoxical fashion, accepting the semi-allogenic placenta, while maintaining host defenses against an array of microbial pathogens. In contrast to the growing evidence that the immune surveillance molecules known as Toll-like receptors (TLRs) are expressed by trophoblasts and fetal membranes, to date, no studies have been conducted on the decidua. Methods: Decidual tissues and cells were obtained from women undergoing first trimester elective terminations or repeat Cesarean sections and analyzed at both the protein and mRNA level. Results: We now demonstrate for the first time that human decidua differentially express TLRs and their downstream signaling molecules as well as TLR stimulated induction of cytokine production in the first and third trimester of pregnancy. Conclusions: These findings suggest that the decidua is a critical component of the innate immune response in pregnancy. Moreover, the results have implications for the success or failure of compromised pregnancies in early or late gestation
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    Increased endometrial expression of CC-chemokine receptor-1 in women with adenomyosis
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Xu, Hong; Yang, Yanfeng; Zhou, Caiyun; Huang, Xiufeng; Lin, Jun; Zhang, Xinmei
    Abnormal endometrial expression of CCchemokine receptor-1 (CCR1) may play a role in the pathogenesis of endometriosis. Adenomyosis, also called endometriosis interna, occurs when the endometrium invades the myometrium. The objective of this study was to determine CCR1 expression in endometrium in women with adenomyosis as compared to women without adenomyosis. We evaluated endometrial mRNA and protein expression in women with and without adenomyosis using quantitative polymerase chain reaction (PCR), immunohistochemical staining and western blot analysis, respectively. We detected CCR1- immunoreactive expression in endometrium in all women with and without adenomyosis. CCR1- immunoreactive staining in endometrial cells was significantly higher in women with adenomyosis (4.89±1.06) compared to those without adenomyosis (2.21±1.16, P<0.001). Women with adenomyosis had higher levels of CCR1 mRNA in endometrium compared to women without adenomyosis (P<0.05). CCR1 protein levels in endometrium were significantly higher in women with adenomyosis (1.66±0.79) compared to women without adenomyosis (0.56±0.13, P<0.001), and positively correlated with the severity of dysmenorrhea (r=0.87, P<0.001). These results suggest that increased CC-chemokine receptor expression may play a role in the pathogenesis of adenomyosis.
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    Lectin binding patterns in normal canine endometrium and in bitches with pyometra and cystic endometrial hyperplasia
    (Murcia : F. Hernández, 2003) Leitner, M.; Aurich, J.E.; Galabova, G.; Aurich, C.; Walter, I.
    Cystic endometrial hyperplasia (CEH) and pyometra in the bitch are dioestral syndromes, supposed to be caused by hormonal disturbances and changes in endometrial steroid hormone receptor levels. Histologically, the endometria show cystic dilated glands and, if bacteria succeed in invading the uterus, pyometra may develop in the following metoestrus. In this study, lectin histochemistry was performed on paraffin sections to compare carbohydrate expression of uterine glands and surface epithelium in healthy dogs and in dogs with CEH and pyometra. Lectin binding is a useful tool to identify glycoconjugates, especially of the glycocalyx, which has essential functions in the endometrium during reproduction. Uterine tissue was obtained from 18 healthy bitches in metoestrus or anoestrus and 18 bitches with a clinical diagnosis of CEH or pyometra. Normal endometria showed cycle-dependent changes in SBA, PNA, HPA and UEA binding during metoestrus and anoestrus. LCA did not show cycle-dependent changes and WGA bound to Golgi regions in the apical parts of surface epithelial cells only in metoestrous. Endometria with inflammatory alterations lost cycle-specific lectin binding patterns and, with increasing severity of pathological changes, showed a marked decrease in binding intensity to the glandular and surface epithelial glycocalyx and secretions. In dogs with CEH, unaltered glands with generally strong lectin binding to the glycocoalyx and Golgi regions were found adjacent to altered glands. The decrease of lectin binding in pyometra cases is supposed to be a result of glandular exhaustion after cystic hyperplasia. In addition, bacterial adhesion to sugar residues on the uterine surface epithelium might impede lectin binding.
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    Local immune response in serous papillary carcinoma of the endometrium
    (Murcia : F. Hernández, 2005) Tamiolakis, D.; Venizelos, J.; Lambropoulou, M.; Nikolaidou, S.; Tsikouras, P.; Jivannakis, T.; Papadopoulos, N.
    Objective: Serous papillary carcinomas of the endometrium are aggressive tumors that tend to permeate, in a very extensive fashion, to uterine and adnexal lymphatic and vascular channels at an early stage in their evolution, and are associated with a particularly gloomy prognosis. It is generally thought that even tumors apparently limited to the endometrium or confined to an endometrial polyp have a poor outcome. Our study points towards the value of HLADR antigen in the outcome of serous papillary endometrial cancer. Our aim was to assess the HLA-DR expression in inactive, endometrial intraepithelial carcinoma (EIC), and invasive serous carcinoma curretage specimens from the endometrial cavity, suggesting a role inimmune response to keep tumor proliferation in check. Study design: Thirty-one cases of inactive endometrium, twelve cases of EIC, and thirtynine cases of serous papillary invasive carcinoma curettings were evaluated for the detection of HLA-DR monoclonal antigen. T helper (TH) marker (CD4) in the tumor stroma of the relevant cases was also studied, given that it is now known that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to TH cells. Results: HLA-DR was expressed in 20 of 31 inactive endometrium (64.5%), 4 of 12 in EIC (33.3%), and in 10 of 39 serous papillary invasive carcinomas (25.6%). CD4 was expressed in 9 of 31 inactive endometrium (29%), 5 of 12 in EIC (42%), and in 26 of 39 serous papillary invasive carcinomas (67%). Conclusions: The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells of inactive endometrium, of EIC and of serous papillary invasive carcinomas agrees with the hypothesis of the inactive endometrium - carcinoma in situ sequence as the usual route for the development of serous papillary invasive carcinoma. The immune attract mechanism by low HLA-DR signaling seems to be of minor importance in the malignant and metastatic potential of the serous papillary endometrial tumours.
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    Maspin expression, subcellular localization and clinicopathological correlation in endometrial hyperplasia and endometrial adenocarcinoma
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Blandamura, Stella; Alessandrini, Lara; Saccardi, Carlo; Giacomelli, Luciano; Fabris, Alberta; Borghero, Angela; Litta, Pietro
    Maspin expression in endometrial hyperplasia and endometrial endometrioid adenocarcinomas was assessed and its correlation with p53 and Ki-67 expressions and clinical outcome, as well as its potential to distinguish typical from atypical endometrial hyperplasia, were assessed in this study. Histological sections from 114 cases of endometrial endometrioid adenocarcinoma, 75 cases of endometrial hyperplasia (typical and atypical), and 23 normal endometrial tissue samples were examined. The most representative hematoxylin-eosin slides were selected and 2-3 micron-thick sections were cut for immunohistochemical staining with maspin, p53, and Ki-67 antibodies. While there was no maspin expression in normal endometrial cells, it was present in 14.5% of the patients with endometrial hyperplasia without atypia. Staining for maspin was positive in atypical hyperplasia and endometrial adenocarcinoma in, respectively, 45% and 49.1% of the cases studied. No statistically significant correlations were found between maspin and Ki-67 antibodies or p53 expression. Our findings showed that maspin expression, which generally correlates with a less aggressive behavior, is significantly higher in atypical hyperplasia and in endometrial endometrioid adenocarcinoma. Maspin positivity in endometrial hyperplasia could be used to identify pseudo-atypical hyperplasia and could be considered a potentially useful prognostic parameter in those cases in which adenocarcinomas are well differentiated.
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    Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis
    (Murcia : F. Hernández, 2005) Walter, I.; Handler, J.; Miller, I.; Aurich, C.
    Periglandular arrangement of myofibroblasts, associated with the deposition of extracellular matrix (ECM), is a cardinal feature of endometrosis in mares. We hypothesized that a disturbance in the expression of matrix degrading enzymes such as matrix metalloproteinases (MMP’s) and matrix cross-linking proteins might lead to an imbalance in deposition and degradation of extracellular matrix components and thereby accentuate degeneration. Therefore, distributions of MMP-2, capable of collagen IV and laminin degradation, and tissue transglutaminase (TG2), a crosslinker of extracellular matrix proteins, were investigated by means of immunohistochemistry on uterine biopsies of healthy mares and animals with endometrosis. It was illustrated that both proteins were present in fibrotic regions of affected endometria, and that they were in most cases colocalized. Periglandular MMP-2 expression was significantly associated with dilated and fibrotic uterine glands. Furthermore, MMP-2 and TG 2 were demonstrated in the stratum compactum of healthy and endometrotic endometria. Gelatin zymography proved that active and inactive pro-form of MMP-2 were present in all examined samples with significantly higher amounts of total and active MMP-2 in affected endometria. TG 2-activity, determined by an in situ assay, was found in cases of severe periglandular fibrosis. We suggest that both enzymes play a major role in changes that occur in ECM homeostasis in endometrial fibrotic regions.
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    Metalloproteinase expression by control and telomerase immortalized human endometrial endothelial cells
    (Murcia : F. Hernández, 2005) Krikun, G.; Mor, G.; Huang, J.; Schatz, F.; Lockwood, C.J.
    Vascular endothelial cells play a critical role in the maintenance of endometrial homeostasis. Indeed many pathological conditions causing abnormal endometrial bleeding including progestin only contraception, hormone replacement therapy, endometrial polyps, myomas, hyperplasia and cancer are associated with aberrant angiogenesis. Critical to the process of angiogenesis is the breakdown of the surrounding tissues by matrix metalloproteases (MMPs). In addition to the cells surrounding the endometrial endothelial cells, the endothelial cells themselves produce their own panel of MMPs. We now characterize the specific MMPs that are expressed by endothelial cells derived from human endometrium. These include MMP-1, MMP-2 and MMP-10 but not MMP-3. In addition, in order to successfully carry out consistent, homogeneous and sufficient numbers of studies we investigated the in vitro expression of the MMPs with both freshly isolated, early passaged endometrial endothelial cells (HEECs) as well as with newly telomerase immortalized HEECs (T-HEECs). The latter were karyotypically normal and expressed classic endothelial cell endpoints such as tubulogenesis on matrigel and expression of the endothelial cell markers CD-31 (PECAM), von Willebrand’s factor, and the Tie-2 receptors. The levels of MMP expression as well as that of the metalloprotease inhibitors TIMP-1 and TIMP-2 were similar in parent and immortalized endothelial cells.
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    Porcine endometrial 3D co-culture: Morphological changes in 3D endometrium tissues according to hormonal changes
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Kim, Sang-Hwan; Park, Yong-Su; Shin, Da-Hye; Moon, Jeong-Chan; Oh, Min-Gee; Yoon, Jong-Taek
    Cells cultured as monolayers proliferate well, but do not sustain their differentiation characteristics. Previous studies have investigated the interactions between cells and growth factors or cytokines by establishing either in vivo or in vitro three-dimensional (3D) cultures. Using porcine uterine epithelial cells and endometrial cells, the current study was designed to develop a 3D uterine culture system and investigate the response to hormone treatment. Formation of the 3D uterine model was similar to that of uterus from the group supplemented with calcium and magnesium, and the addition of these ions altered the spectrum of basement membrane degrading enzyme expression and activity. In particular, the epithelial cell junctions in the 3D model most closely resembled those of an actual uterus when the medium was supplemented with calcium and magnesium; the intercellular basement membrane structure was also tall under these conditions. The study confirmed that Casp-3 expression was lowest in the P4 (progesterone) treatment group, and this hormone was the most potent stimulus for formation of the endometrial cell layer. Therefore, the addition of calcium and magnesium plays an important role in the formation of a 3D uterine model, and the addition of P4 hormone mimics uterine thickening by stimulating growth of the epithelial cell layer.
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    Regulation of human endometrial transforming growth factor ß1 and ß3 isoforms through menstrual cycle and medroxyprogesterone acetate treatment
    (Murcia : F. Hernández, 2002) Reis, F.M.; Ribeiro, M.F.M.; Maia, A.L.; Spritzer, P.M.
    The progesterone-induced differentiation of endometrial tissue from proliferative into secretory and decidua seems to be modulated by locally produced hormones and cytokines. Transforming growth factor beta (TGFß), a cytokine produced by endometrial cells, has been shown to modulate endometrial cell proliferation in vitro. Our aim was to evaluate the effects of medroxyprogesterone acetate (MPA) and the influence of menstrual cycle on the expression of TGFß1 and TGFß3 in human endometrium in vivo. In a doubleblind, placebo-controlled trial, 46 healthy women with regular menstrual cycles received either MPA (10 mg/day) or placebo during 10 days. Endometrial and blood samples were collected 8-12 hours after the last MPA or placebo administration. Patients were classified into three groups according to biopsy dating and treatment: proliferative [tissue]/placebo, secretory [tissue]/placebo and secretory [tissue]/MPA. The immunohistochemical distribution of TGFß1 and TGFß1 mRNA was similar in all groups. Immunoreactive TGFß3 was present in the epithelium in 9.1% of proliferative samples, in 41.2% of secretory/placebo samples and in 87.5% of secretory/MPA samples (p=0.001). In the stroma, the frequency of TGFß3 staining was markedly increased after treatment with MPA (62.5%) compared to placebo (proliferative: 9.1%; secretory: 5.9%; p=0.005). The levels of TGFß3 mRNA increased during the secretory phase and were higher in the MPA-treated group, being directly correlated with morphological endometrial differentiation. It is concluded that MPA administration to healthy women increased TGFß3 but did not change TGFß1 gene and protein expression in the endometrium. This finding suggests that TGFß3 may be a local factor mediating progesterone- and progestogen-induced endometrial differentiation.
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    Seminal Plasma Modifies the Transcriptional Pattern of the Endometrium and Advances Embryo Development in Pigs
    (2019-12-18) Martínez, Cristina A.; Cambra, Josep M.; Parrilla, Inmaculada; Roca, Jordi; Ferreira-Dias, Graça; Pallarés, Francisco J.; Lucas, Xiomara; Vázquez, Juan M.; Martínez, Emilio A.; Gil, María A.; Rodríguez-Martínez, Heriberto; Cuello, Cristina; Álvarez-Rodríguez, Manuel; Medicina y Cirugía Animal
    Background: Seminal plasma (SP) promotes sperm survival and fertilizing capacity, and potentially affects embryo development, presumably via specific signaling pathways to the internal female genital tract. Objectives: This study evaluated how heterologous SP, infused immediately before postcervical artificial insemination (AI) affected embryo development and the transcriptional pattern of the pig endometria containing embryos. Materials and Methods: Postweaning estrus sows (n = 34) received 40-mL intrauterine infusions of either heterologous pooled SP or Beltsville Thawing Solution (BTS; control) 30 min before AI of semen extended to 10% of homologous SP. Embryos (all sows) and endometrium samples (3 sows/group) were removed during laparotomy 6 days after the infusion of SP or BTS to morphologically evaluate the embryos to determine their developmental stage and to analyze the endometrial transcriptome using microarrays (PORGENE 1.0 ST GeneChip array, Affymetrix) followed by qPCR for further validation. Results: Embryo viability was equal between the groups (~93%), but embryo development was significantly (P < 0.05) more advanced in the SP-treated group compared to control. A total of 1,604 endometrium transcripts were differentially expressed in the SP group compared to the control group. An enrichment analysis showed an overrepresentation of genes and pathways associated with the immune response, cytokine signaling, cell cycle, cell adhesion, and hormone response, among others. Conclusions: SP infusions prior to AI positively impacted the preimplantation embryo development and altered the expression of the endometrial genes and pathways potentially involved in embryo development.
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    Stem cells: Are they the answer to the puzzling etiology of endometriosis?
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Oliveira, Flávia R.; Dela Cruz, Cynthia; Del Puerto, Helen L.; Vilamil, Quésia T.M.F.; Reis, Fernando M.; Camargos, Aroldo F.
    Endometriosis is a chronic bening disease characterizaed by the presence of abnormally located tissue resembling the endometrium with glands and stroma. This disease has a high degree of morbidity due to chronic pelvic pain and infertility. The disease is likely to be polygenic and multifactorial, but the exact pathogenic mechanisms are still not entirely clear. Recently, adult stem cells have been identified in several tissues, including the endometrium. These cells are probably involved in the regenerative ability of the endometrial cycle, and also in the pathogenesis of proliferative gynaecological diseases, such as endometriosis. The identification of stem cells in animal and human tissues is very complex and the putative stem cells are supposed to be found through several assays such as clonogenicity, label-retaining cells, “side- population” cells, undifferentiation markers, and cellular differentiation. Bone marrow-derived stem cells transplanted into humans and animals have also been identified in eutopic endometrium and endometriotic implants. This review evaluates the available evidence regarding stem/progenitor cells in the human endometrium and explores the possible involvement of these cells in the etiology of endometriosis.
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    Steroid receptors ERa, ERß, PR-A and PR-B are differentially expressed in normal and atrophic human endometrium
    (Murcia : F. Hernández, 2012-05-21) Mylonas, I.; Jeschke, U.; Shabani, N.; Kuhn, C.; Kunze, Sussane; Dian, D.; Friedl, C.; Kupka, M.S.; Friese, K.
    Objective: The endometrium expresses estrogen (ER) and progesterone receptor (PR), which are related to autocrine and paracrine processes that respond to estrogen and progesterone. Therefore, the aim of this study was to evaluate the distribution pattern of ERa, ERß, PR-A and PR-B with monoclonal antibodies in normal human endometrial tissue. Study Design: Human endometrial tissue was obtained from 84 premenopausal and 11 postmenopausal patients and immunohistochemically analysed with monoclonal antibodies against ERa, ERß, PR-A and PR-B. Results: ERa, PR-A and PR-B declined significantly (p<0.001, p<0.05, p<0.05 respectively) in glandular epithelium from proliferative to late secretory phase. The ERß immunohistochemical reaction showed a similar significant declining pattern (p<0.05), although the staining intensity was lower than that of ERa. While ERa, ERß and PR-B decrease significantly in atrophic endometrial tissue compared to proliferative endometrium, a significant up-regulation of PR-A was observed compared to late secretory phase (p<0.05). Conclusion: ERa, ERß, PR-A and PR-B were expressed in normal human endometrium with a cyclical variation during the menstrual cycle. In normal postmenopausal endometrial tissue, a down-regulation of ERa, ERß and PR-B occurs with a subsequent higher expression of PRA. These results show the presence of steroid receptors in human epithelium, indicating that these cells respond to estrogen and progesterone, thus playing a significant role in endometrial physiology.
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    Open Access
    Unusual inflammation in gynecologic pathology associated with defective endometrial receptivity
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Kitaya, Kotaro Kitaya; Yasuo, Tadahiro; Tada, Yoshihiro; Hayashi, Terumi; Iwaki, Yuri; Karita, Masako; Funabiki, Miyako; Taguchi, Sagiri; Spillers, Dustin; Nakamura, Yoshitaka; Yamada, Hisao
    Human cycling endometrium displays a series of periodic transitions unique to this mucosal tissue, which includes rapid proliferation, secretory transformation, physiological angiogenesis, interstitial edema, and menstrual shedding. Among these properties of the endometrium are the inflammatory changes that occur dynamically across the menstrual cycle. Immunocompetent cell composition and inflammatory gene expression pattern in the human endometrium drastically fluctuate from the proliferative phase to the secretory phase, particularly at the time of ovulation. These local immune responses are fine-tuned by the direct or indirect action of two representative ovarian steroids, estradiol and progesterone, and are essential for successful blastocyst implantation. Meanwhile, studies have been accumulating the evidence that such physiological endometrial inflammatory status is altered in the presence of certain gynecologic pathologies. Given that blastocysts are semi-allografts for maternal tissue, even subtle alterations in endometrial immunity potentially have a negative impact on implantation process. In this article, we aimed to review and discuss the physiological and pathological mucosal inflammatory conditions that can affect endometrial receptivity.

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