Differentiating Human Endometrial Cells Acquire Resistance to IFNγ Signalling: Role of the Progesterone Receptor (PR) and Protein Inhibitor of Activated Stat (PIASy)

2003 ◽  
Vol 104 (s49) ◽  
pp. 64P-64P
Author(s):  
Jan J Brosens ◽  
Georgia Zoumpoulidou ◽  
Mark Christian
Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3217
Author(s):  
Robert Rekawiecki ◽  
Karolina Dobrzyn ◽  
Magdalena K. Kowalik

Nuclear receptor coregulators include coactivators and corepressors which associate with the progesterone receptor (PGR) during its activation. Fluctuations in the transcription levels of their respective genes and subsequent protein production as well as in related activities for histone acetyltransferase (HAT) and histone deacetylase (HDAC) can affect PGR function and thus change the action of progesterone (P4) in bovine endometrium during the estrous cycle. Endometrial tissue on days 2–5, 6–10, 11–16, and 17–20 of the estrous cycle was used for determination of the mRNA expression levels of coactivators P300, CREB, and SRC-1 along with corepressor NCOR-2 using Real-Time PCR, with protein levels by Western blot. Coregulators cellular localizations were assessed by immunohistochemistry whereas the activities of HAT and HDAC by using EIA. The highest levels of mRNA and proteins for all of the investigated coregulators, as well as the highest levels of activity for HAT and HDAC, were detected over days 2–16 of the estrous cycle. All of the tested coregulatory proteins were localized in the nuclei of endometrial cells. This research indicates the important role of coregulators of the PGR receptor in regulating P4 activity in endometrial cells, especially during the pre-implantation period.


2021 ◽  
Vol 2 (2) ◽  
pp. 68-84
Author(s):  
Marwan Habiba ◽  
Donatella Lippi ◽  
Giuseppe Benagiano

Through microscopy, early researchers identified the epithelium on the inner surfaces of the uterus, cervix and Fallopian tubes. The identification of ectopic epithelium was gradual, starting from the gross pathology study of unusual cystic lesions. Towards the end of the nineteenth century, attention focused on the epithelium as a critical component. The term ‘adenomyoma’ was coined around eighteen eighty to designate the majority of mucosa-containing lesions. Several theories were advanced to explain its aetiology. In the main, lesions were considered to arise from invasion from uterine epithelium; implantation of endometrium through retrograde menstruation; hematogenous or lymphatic spread; or from embryonic remnants. Although initially widely rejected, around 1920, an almost unanimous consensus formed on the endometrial nature of epithelial invasions. During the following years, adenomyosis and endometriosis came to be used to distinguished lesions within or outside the uterus. Adenomyosis was attributed to direct infiltration of uterine mucosa into the myometrium, and endometriosis to the implantation of endometrial cells and stroma into the peritoneal cavity through retrograde menstruation. Around the same time, ovarian lesions, initially described as ovarian hematomas or chocolate cysts, were regarded as a form of endometriosis. Three variants of endometriosis were thus described: superficial peritoneal, deep nodular and ovarian endometriomas. Ectopic epithelium has long been recognised as having similarities to tubal, or cervical epithelium. Lesions containing mixed epithelium are often termed Müllerianosis. This article demonstrates the stepwise evolution of knowledge, the role of the pioneers and the difficulties that needed to be overcome. It also demonstrates the value of collaboration and the inter-connected nature of the scientific endeavour.


Author(s):  
Dariusz Szukiewicz ◽  
Aleksandra Stangret ◽  
Carmen Ruiz-Ruiz ◽  
Enrique G. Olivares ◽  
Olga Soriţău ◽  
...  

AbstractEndometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis.


2021 ◽  
Vol 22 (11) ◽  
pp. 5827
Author(s):  
Jae Chul Lee ◽  
Sung Hoon Kim ◽  
Young Sang Oh ◽  
Ju Hee Kim ◽  
Sa Ra Lee ◽  
...  

Although endometriosis is a benign disease characterized by the presence of endometrial tissues outside the uterus, ectopic endometrial cells can exhibit malignant biological behaviors. Retinol-binding protein4 (RBP4) is a novel adipocyte-derived cytokine, which has important roles in regulating insulin sensitivity and energy metabolism. RBP4 is a potent modulator of gene transcription, and acts by directly controlling cell growth, invasiveness, proliferation and differentiation. Here, we evaluated the possible role of RBP4 in the pathogenesis of endometriosis. We compared the levels of RBP4 in the tissues and peritoneal fluid (PF) of women with and without endometriosis and evaluated the in vitro effects of RBP4 on the viability, invasiveness, and proliferation of endometrial stromal cells (ESCs). RBP4 levels were significantly higher in the PF of the women in the endometriosis group than in the controls. RBP4 immunoreactivity was significantly higher in the ovarian endometriomas of women with advanced stage endometriosis than those of controls. In vitro treatment with human recombinant-RBP4 significantly increased the viability, bromodeoxyuridine expression, and invasiveness of ESCs. Transfection with RBP4 siRNA significantly reduced ESC viability and invasiveness. These findings suggest that RBP4 partakes in the pathogenesis of endometriosis by increasing the viability, proliferation and invasion of endometrial cells.


Author(s):  
Honoree Fleming ◽  
Rebekah Condon ◽  
Genevieve Peterson ◽  
Ilse Guck ◽  
Elizabeth Prescott ◽  
...  

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (6) ◽  
pp. 93-100
Author(s):  
Victor E. Radzinsky ◽  
Mekan R. Orazov ◽  
Liliia R. Toktar ◽  
Liudmila M. Mihaleva ◽  
Pavel A. Semenov ◽  
...  

Chronic endometritis (CE) is defined as a state of inflammation localized in the endometrium, accompanied by edema, dissociated maturation of epithelial cells and fibroblasts, increased stromal density and the presence of plasma cell infiltrate in it. The connection between chronic inflammation in the endometrium and infertility deserves special attention. Inadequate response of immunocompetent endometrial cells, including impaired synthesis of proinflammatory cytokines, dysreceptiveness, disorders of proliferation and differentiation processes are the main links in the formation of infertility in patients with CE. Despite the fact that the presence of a normocenosis of the uterine cavity today is not in doubt this is a physiological norm, persistent bacterial infection of the endometrium is still called the main etiopathogenetic factor of CE and, therefore, the main point of application of therapeutic agents. Nevertheless, a number of works have emphasized the special role of not bacterial, but viral etiology of endometritis, especially in the context of infertility developing against this background. It seems that the role of viral endometrial infection in adverse pregnancy outcomes and in vitro fertilization programs is underestimated. Further research is needed to clarify the relationship of viral infection as a trigger of implantation failure in infertile women with CE.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
C. Mannelli ◽  
F. Ietta ◽  
C. Carotenuto ◽  
R. Romagnoli ◽  
A. Z. Szostek ◽  
...  

A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA). As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end,in vitrodecidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2) was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%). After 24–48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin (β-hCG) and cytokine Macrophage Migration Inhibitory Factor (MIF). The results showed that direct exposure to BPA stimulated the release of both MIF andβ-hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance ofin vitromodels including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.


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