Par3/Integrin β1 regulates embryo adhesion via changing endometrial luminal epithelium polarity

2021 ◽  
Author(s):  
Jiali Peng ◽  
Xiaoling Li ◽  
Yan Zhang ◽  
Jian Hu ◽  
Yunjie Shang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Polarity ◽  
Research Laboratory ◽  
Ovarian Hormones ◽  
University Research ◽  
Luminal Epithelium ◽  
Integrin Β1 ◽  
Endometrial Epithelial Cell ◽  
Epithelial Cell Lines ◽  
Endometrial Epithelial Cells

Abstract Objective To investigate the pathophysiological significance of Par3 and integrin β1 with regards to the functionality of the endometrial luminal epithelium (LE). Design Laboratory study. Setting University research laboratory. Patients Analysis involved endometrial aspirates and human endometrial epithelial cells (HEC-1A cells and RL95–2 cells). Interventions We first examined the expression and localization of Par3 and integrin β1 in HEC-1A cells and RL95–2 cells. Then we knocked down Par3 and integrin β1 in HEC-1A cells and RL95–2 cells respectively and found that Par3/integrin β1 affected embryo adhesion by regulating the intercellular tight junctions (TJs) structure and thus the polarity of endometrial LE. These findings were also confirmed in endometrium specimens from human and mice. Main Outcome Measures The expression and localization of Par3 and integrin β1 in endometrial epithelial cell lines and endometrium specimens. The regulations of Par3 and integrin β1 on TJs, polarity and embryo adhesion. Results Following the knockdown of Par3 in HEC-1A cells, there was a reduction in the complexity of the TJs and cell polarity, and the adhered blastocysts number was significantly increased. However, the reduction of integrin β1 in RL95–2 cells resulted in effects that directly opposed those following the knockdown of Par3 in HEC-1A cells. Estrogen and progesterone reduced the expression of Par3 and promoted the expression of integrin β1 in HEC-1A cells. Conclusions Par3/integrin β1 regulates embryo adhesion by regulating intercellular TJs structure and polarity of endometrial LE under the action of ovarian hormones.

scholarly journals Oxytocin Receptor Down-Regulation Is Not Necessary for Reducing Oxytocin-Induced Prostaglandin F2α Accumulation by Interferon-τ in a Bovine Endometrial Epithelial Cell Line

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 897-905 ◽  
Author(s):  
Narayanan Krishnaswamy ◽  
Ghislain Danyod ◽  
Pierre Chapdelaine ◽  
Michel A. Fortier
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Prostaglandin F2α ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Down Regulation ◽  
Endometrial Epithelial Cell ◽  
Endometrial Epithelial Cells

Interferon-τ (IFNτ) is the embryonic signal responsible for pregnancy recognition in ruminants. The primary action of IFNτ is believed to be mediated through inhibition of prostaglandin F2α (PGF2α) released from the endometrial epithelial cells in response to oxytocin (OT). Our working hypothesis was that the antiluteolytic effect of IFNτ also involved modulation of PG production downstream of OT receptor (OTR) and/or cyclooxygenase 2 (COX2). There is currently no OT-sensitive endometrial cell line to study the molecular mechanisms underlying our hypotheses. Therefore, we established an immortalized bovine endometrial epithelial cell line (bEEL) exhibiting OT response. These cells were cytokeratin positive, expressed steroid receptors, and exhibited preferential accumulation of PGF2α over PGE2. The bEEL cells were highly sensitive to OT, showing time- and concentration-dependent increase in COX2 transcript and protein and PGF2α accumulation. Interestingly, IFNτ (20 ng/ml) significantly reduced OT-induced PGF2α accumulation, but surprisingly, the effect was not mediated through down-regulation of either OTR or COX2. Rather, IFNτ up-regulated COX2 in a time- and concentration-dependent manner while decreasing OT-induced PG accumulation. This suggests that COX2 is not a primary target for the antiluteolytic effect of IFNτ. Because IFNτ reduced OT-stimulated PGF2α accumulation within 3 h, the mechanism likely involves a direct interference at the level of the OT signaling or transcription in addition to the down-regulation of OTR observed in vivo. In summary, bEEL cells offer a unique in vitro model for investigating the cellular and molecular mechanisms underlying OT and IFNτ response in relation with luteolysis and recognition of pregnancy in the bovine. Interferon-τ acts as a competitive partial agonist, stimulating basal but inhibiting oxytocin- and phorbol myristate acetate-stimulated prostaglandin F2α production in immortalized bovine endometrial epithelial cells.

Expression and function of Toll-like receptors in human endometrial epithelial cell lines

2010 ◽  
Vol 84 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Wedad Aboussahoud ◽  
Reza Aflatoonian ◽  
Chris Bruce ◽  
Sarah Elliott ◽  
Jon Ward ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Toll Like Receptors ◽  
Endometrial Epithelial Cell ◽  
Epithelial Cell Lines ◽  
And Function

Differential expression of 17beta-hydroxysteroid dehydrogenases types 2 and 4 in human endometrial epithelial cell lines

2000 ◽  
Vol 24 (1) ◽  
pp. 135-144 ◽  
Author(s):  
B Husen ◽  
N Psonka ◽  
M Jacob-Meisel ◽  
C Keil ◽  
GM Rune
Keyword(s):  
Epithelial Cell ◽  
Mrna Expression ◽  
Differential Expression ◽  
Cell Lines ◽  
Calf Serum ◽  
Human Endometrium ◽  
Rt Pcr ◽  
Serum Replacement ◽  
Endometrial Epithelial Cell ◽  
Epithelial Cell Lines

In the endometrium two enzymes are known to convert estradiol to its inactive metabolite estrone: microsomal 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) and peroxisomal 17beta-HSD4. In order to elucidate the particular function of each of these two different enzymes, the human endometrial epithelial cell lines HEC-1-A and RL95-2 were examined with respect to the expression of 17betaHSD isozymes. They were compared with human endometrium in vivo. Non-radioactive in situ hybridization revealed both enzymes in glandular epithelial cells of human endometrium. The two cell lines were screened for mRNA expression of 17beta-HSD 1-4 by RT-PCR and Northern blot. 17beta-HSD2 and 4 could be detected by either method, 17beta-HSD1 only by RT-PCR, 17beta-HSD3 not at all. Both cell lines were proven to have no receptor for progesterone which is known as a physiological inducer of several 17beta-HSD isozymes. To study the regulation of 17beta-HSD2 and 17betaHSD4, the concentration of fetal calf serum in the cell culture media was reduced stepwise to 0.3% by dilution with a defined serum replacement. This treatment led to an inhibition of 17beta-HSD2 mRNA expression and an increase in the mRNA expression of 17beta-HSD4. Concomitantly, distinct morphological changes were observed, such as a decrease in the number and length of microvilli and a decrease in the formation of domes on top of the monolayers. The endometrial epithelial cell lines HEC-1-A and RL95-2 represent a suitable in vitro model for further studies of the differential expression of the major endometrial HSD isozymes, independent of the effect of progesterone.

Cell surfactomes of two endometrial epithelial cell lines that differ in their adhesiveness to embryonic cells

2014 ◽  
Vol 81 (4) ◽  
pp. 326-340 ◽  
Author(s):  
Sonali R. Bhagwat ◽  
Tejashree Redij ◽  
Kruttika Phalnikar ◽  
Sumeet Nayak ◽  
Swati Iyer ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Embryonic Cells ◽  
Endometrial Epithelial Cell ◽  
Epithelial Cell Lines

scholarly journals The effects of sex steroid hormones and interleukin-1-beta on MUC1 expression in endometrial epithelial cell lines

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 733-742 ◽  
Author(s):  
A W Horne ◽  
E-N Lalani ◽  
R A Margara ◽  
J O White
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Interleukin 1 ◽  
Flow Cytometric Analysis ◽  
Endometrial Receptivity ◽  
Muc1 Expression ◽  
Interleukin 1 Beta ◽  
Similar Treatment ◽  
Endometrial Epithelial Cell ◽  
Epithelial Cell Lines

Oestrogen, progesterone and paracrine signals from the embryo have been associated with the overall control of implantation. Changes in the expression of the heavily glycosylated transmembrane glycoprotein MUC1 mucin on the endometrial epithelium are also thought to be important for embryo attachment. Increased MUC1 expression has been correlated with elevated progesterone levels in the secretory phase of the menstrual cycle. Embryonic control of endometrial receptivity through changes in MUC1 expression could be achieved through the interleukin-1 system. Four endometrial epithelial cell lines (HEC1A, HEC1B, Ishikawa and RL592) were treated with oestrogen and progesterone (with or without interleukin-1-beta) and were subjected to immunocytochemistry and flow cytometric analysis to determine MUC1 production using MUC1 antibodies. HEC1A (oestrogen receptor (ER) and progesterone receptor (PR) positive) and HEC1B (ER positive and PR negative) were transfected with theMUC1promoter, underwent similar treatment regimes and the activity of theMUC1promoter relative to their untreated controls was determined using a chloramphenicol acetyltransferase (CAT) enzyme-linked immunoassay. Using the cell lines, we determined that endometrial MUC1 expression is up-regulated by progesterone, consistent with thein vivoincreases in MUC1 related to high progesterone levels. We also revealed that neither oestrogen, nor interleukin-1-beta, appear to modulate MUC1. Progesterone-dependent regulation of MUC1 is likely to be an important factor in determining endometrial receptivity.

Human endometrial epithelial cell lines for studying steroid and cytokine actions

1990 ◽  
Vol 26 (12) ◽  
pp. 1173-1179 ◽  
Author(s):  
S. Tabibzadeh ◽  
K. L. Kaffka ◽  
P. L. Kilian ◽  
P. G. Satyaswaroop
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Endometrial Epithelial Cell ◽  
Epithelial Cell Lines

Murine polycystic kidney epithelial cell lines have increased integrin-mediated adhesion to collagen

1994 ◽  
Vol 267 (6) ◽  
pp. F1082-F1093 ◽  
Author(s):  
J. van Adelsberg
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Cell Polarity ◽  
Cell Lines ◽  
Autosomal Recessive ◽  
Polycystic Kidney ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Epithelial Cell Lines ◽  
Cell Matrix Interactions

Polycystic kidney disease (PKD), in which epithelial cysts arise from or instead of normal renal tubules, is one of the most common genetic diseases. It has both autosomal dominant and autosomal recessive inheritance in humans and in experimental animals. Epithelial cells lining the cysts have an increased rate of proliferation, abnormal polarity of Na-K-adenosinetriphosphatase, which is localized to apical and sometimes lateral membrane domains, and an abnormal extracellular matrix. One hypothesis that explains the simultaneous acquisition of these characteristics as the result of several different genetic mutations is that cell-matrix interactions, which are known to regulate cell proliferation and cell polarity, are altered in PKD. I have created immortalized renal epithelial cell lines from C57Bl/6Jcpk mice with PKD, an autosomal recessive trait in these animals, and from their phenotypically normal littermates. Using these cell lines, I show that polycystic cells have increased adhesion to collagens and laminin mediated by an integrin. These results demonstrate that cell-matrix interactions are defective in PKD and suggest that these interactions may be involved in the abnormalities of cell polarity and cell proliferation seen in these disorders.

scholarly journals Interleukin-11 and Leukemia Inhibitory Factor Regulate the Adhesion of Endometrial Epithelial Cells: Implications in Fertility Regulation

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2915-2923 ◽  
Author(s):  
M. Marwood ◽  
K. Visser ◽  
L. A. Salamonsen ◽  
E. Dimitriadis
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Leukemia Inhibitory Factor ◽  
Embryo Implantation ◽  
Neutralizing Antibody ◽  
Collagen Iv ◽  
Inhibitory Factor ◽  
Endometrial Epithelial Cell ◽  
Endometrial Epithelial Cells

Embryo implantation requires the closely harmonized processes of apposition, attachment, and adhesion of the conceptus to the maternal endometrial epithelium. IL-11 and leukemia inhibitory factor (LIF), two IL-6 family cytokines, are produced by the endometrium and are absolutely required for implantation in mice. We examined the effect of IL-11 and LIF on human endometrial epithelial cell adhesion. Both cytokines increased adhesion of primary human endometrial epithelial cells to fibronectin and collagen IV. IL-11 stimulated, whereas LIF had no effect on the adhesion of trophoblast to endometrial epithelial cells. Focused oligogene arrays were used to identify extracellular matrix and adhesion molecules mRNAs regulated by endometrial epithelial cells. We demonstrated by real-time RT-PCR and antibody arrays that both cytokines increased integrin-α2 mRNA and protein by endometrial epithelial cells. Signal transducers and activators of transcription (STAT)-3 inhibition reduced IL-11- and LIF-mediated epithelial cell adhesion to fibronectin, suggesting both cytokines regulated adhesion via phosphorylation of STAT3. Addition of either IL-11 neutralizing antibody and IL-11 or LIF and LIF antagonist to endometrial epithelial cells abolished cytokine induced phosphorylated STAT3. LIF but not IL-11 induced adhesion to collagen IV was reduced by an integrin-α2β1 neutralizing antibody. This study demonstrated that IL-11 and LIF regulated endometrial epithelial cell adhesion, suggesting that targeting IL-11 and LIF may be useful in regulating fertility by either enhancing or blocking implantation.

scholarly journals Mouse double minute homologue 2 (MDM2) downregulation by miR-661 impairs human endometrial epithelial cell adhesive capacity

2018 ◽  
Vol 30 (3) ◽  
pp. 477 ◽  
Author(s):  
Amy Winship ◽  
Amanda Ton ◽  
Michelle Van Sinderen ◽  
Ellen Menkhorst ◽  
Katarzyna Rainczuk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Endometrial Cells ◽  
Endometrial Epithelial Cell ◽  
Mouse Double Minute ◽  
Double Minute ◽  
Ishikawa Cells ◽  
Endometrial Epithelial Cells

Human blastocysts that fail to implant following IVF secrete elevated levels of miR-661, which is taken up by primary human endometrial epithelial cells (HEECs) and impairs their adhesive capability. MicroRNA miR-661 downregulates mouse double minute homologue 2 (MDM2) and MDM4 in other epithelial cell types to activate p53; however, this has not been examined in the endometrium. In this study MDM2 protein was detected in the luminal epithelium of the endometrium, the site of blastocyst attachment, during the mid secretory receptive phase of the menstrual cycle. The effects of miR-661 on gene expression in and adhesion of endometrial cells was also examined. MiR-661 overexpression consistently downregulated MDM2 but not MDM4 or p53 gene expression in the Ishikawa endometrial epithelial cell line and primary HEEC. Adhesion assays were performed on the real-time monitoring xCELLigence system and by co-culture using Ishikawa cells and HEECs with HTR8/SVneo trophoblast spheroids. Targeted siRNA-mediated knockdown of MDM2 in endometrial epithelial cells reduced Ishikawa cell adhesion (P < 0.001) and also reduced HTR8/SVneo trophoblast spheroid adhesion to Ishikawa cells (P < 0.05) and HEECs (P < 0.05). MDM2 overexpression using recombinant protein treatment resulted in enhanced HTR8/SVneo trophoblast spheroid adhesion to Ishikawa cells (P < 0.01) and HEECs (P < 0.05). This study highlights a potential new mechanism by which human blastocyst-secreted miR-661 reduces endometrial epithelial cell adhesion; via downregulation of MDM2. These findings suggest that MDM2 contributes to endometrial–blastocyst adhesion, implantation and infertility in women.

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