Showing papers on "Decidual cells published in 2012"
TL;DR: Autocrine as well as paracrine factors regulating invasion of extravillous trophoblasts and critical signaling cascades involved are summarized and key regulatory transcription factors controlling cell column proliferation and differentiation of the human extravillus trophoblast are focused on.
140 citations
TL;DR: The data indicate that chemerin is up-regulated during decidualization and might contribute to NK cell accumulation and vascular remodeling during early pregnancy.
Abstract: Context: Although decidual natural killer (NK) cell accumulation and vascular remodeling are critical steps to ensure successful pregnancy, the molecular mechanisms controlling these events are poorly defined. Objective: Herein we analyzed whether chemerin, a recently identified chemoattractant involved in many pathophysiological processes, could be expressed in the uterine compartment and could regulate events relevant for the good outcome of pregnancy. Design: Chemerin expression in human primary culture of stromal (ST) cells, extravillous trophoblast cells, and decidual endothelial cells (DEC) was analyzed by RT-PCR, ELISA, and Western blot. Migration through ST or DEC of peripheral blood and decidual (d) NK cells from pregnant women was performed using a transwell assay. A DEC capillary-like tube formation assay was used to evaluate endothelial morphogenesis. Results: Chemerin is differentially expressed by decidual cells during early pregnancy being present at high levels in ST and extravillous troph...
71 citations
TL;DR: It is proposed that in the endometrium, Notch has a dual role during the window of uterine receptivity, and down-regulation may be critical for the transition of stromal fibroblast to decidual cells, which is essential for the establishment of a successful pregnancy.
Abstract: No other tissue in the body undergoes such a vast and extensive growth and remodeling in a relatively short period of time as the primate endometrium. Endometrial integrity is coordinated by ovarian hormones, namely, estrogens, progesterone, and the embryonic hormone chorionic gonadotropin (CG). These regulated events modulate the menstrual cycle and decidualization. The Notch family of transmembrane receptors regulate cellular proliferation, differentiation, and apoptosis, cellular processes required to maintain endometrial integrity. In two primate models, the human and the simulated pregnant baboon model, we demonstrated that Notch1 is increased during the window of uterine receptivity, concomitant with CG. Furthermore, CG combined with estrogens and progesterone up-regulate the level of Notch1, whereas progesterone increases the intracellular transcriptionally competent Notch1, which binds in a complex with progesterone receptor. Inhibition of Notch1 prevented decidualization, and alternatively, when decidualization is biochemically recapitulated in vitro, Notch1 is down-regulated. A focused microarray demonstrated that the Notch inhibitor, Numb, dramatically increased when Notch1 decreased during decidualization. We propose that in the endometrium, Notch has a dual role during the window of uterine receptivity. Initially, Notch1 mediates a survival signal in the uterine endometrium in response to CG from the implanting blastocyst and progesterone, so that menstrual sloughing is averted. Subsequently, Notch1 down-regulation may be critical for the transition of stromal fibroblast to decidual cells, which is essential for the establishment of a successful pregnancy.
69 citations
TL;DR: IL-6 stimulated phosphorylation of several cell signalling proteins in EVT (8-14 weeks' gestation), although significance was lost after correction for multiple comparisons, and it inhibited secretion of RANTES involved in a number of cellular processes.
Abstract: Invasion of uterine tissues by extravillous trophoblast cells (EVT) is essential for successful human pregnancy. EVT invasion is tightly regulated by a number of factors, including growth factors and cytokines, but the mechanisms that underlie their regulatory effect remain poorly understood. Interleukin (IL)-6 has been suggested to play a role in controlling EVT invasion. We hypothesized that IL-6 produced by cells in uterine decidua would regulate EVT invasiveness via IL-6Rα and gp130 receptors expressed by trophoblast cells. The effect of IL-6 on EVT signalling and cytokine production was also studied. Supernatants from disaggregated 'total' decidual cells, CD8(+) T cells, CD10(+) decidual stromal cells, CD14 macrophages, CD56(+) uterine natural killer cells, cytotrophoblast and EVT cells contained large quantities of IL-6 protein at both 8-10 and 12-14 weeks gestational age. IL-6Rα and gp130 were immunolocalized to EVT in placental bed biopsies from 8 to 20 weeks gestation and IL-6Rα expression was confirmed by western blotting. IL-6 had no effect on the invasive potential of EVT from chorionic villi or the immortalized EVT cell line HTR-8/SVneo in a Matrigel(®) invasion assay. IL-6 stimulated phosphorylation of several cell signalling proteins in EVT (8-14 weeks' gestation), although significance was lost after correction for multiple comparisons. Incubation with IL-6 decreased secretion of regulated upon activation, normal T-cell expressed and secreted (RANTES) by EVT cells. In conclusion, although IL-6 did not affect trophoblast cell invasion, it stimulated EVT cellular cascades and inhibited secretion of RANTES involved in a number of cellular processes.
63 citations
TL;DR: It is shown that although both RRM1 and RRM2 expression are markedly induced in mouse uterine stromal cells undergoing decidualization, only RRM 2 is regulated by progesterone, a key regulator of decidUALization.
59 citations
TL;DR: MIC-1 is identified as a novel factor (secreted by decidual cells in early pregnancy) that could promote the increase of a tolerogenic subtype of DC in decidua that could help in the development of pro-fetal tolerance in pregnancy.
Abstract: background: Macrophage inhibitory cytokine-1 (MIC-1) is a multifunctional cytokine produced in high amounts by placental tissue. Inhibiting trophoblast invasion and suppressing inflammation through inhibition of macrophage activation, MIC-1 is thought to provide pleiotropic functions in the establishment and maintenance of pregnancy. So far, little is known about the decidual cell subsets producing MIC-1 and the effect of this cytokine on dendritic cells (DCs), which are known to play a distinct role in the development of pro-fetal tolerance in pregnancy. methods: To identify the decidual cell types expressing and secreting MIC-1, immunohistochemical staining, PCR experiments, western blot analysis and ELISAs were performed. Immature DCs (iDCs) were generated from peripheral blood-derived monocytes and differentiated in the presence of MIC-1 or dexamethasone (Dex) for control. Migratory and proliferative activity of DCs after MIC-1 exposure was investigated by migration and proliferation assay. Cytokine secretion after MIC-1 exposure was tested in isolated uNK cells, isolated CD14+ monocytes, monocyte-derived iDCs and mature DCs. Subsequently, the phenotype of DCs was studied using FACS analysis. To test the T-cell stimulatory capacity of pre-incubated DCs, mixed lymphocyte reaction was applied. Finally, the expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) after the exposure of MIC-1 to maturing DCs was analysed by western blot. results: Immunohistochemical staining, PCR and western blot experiments demonstrated that MIC-1 is mainly expressed by trophoblast cells and decidual stromal cells. Analysis of the MIC-1 secretion of decidual cell types by ELISA again characterized trophoblast and stromal cells as main producers. The migratory activity of iDCs was significantly induced by MIC-1. No changes in proliferative activity of DCs were observed after MIC-1 pre-incubation. The secretion of pro- or anti-inflammatory cytokines was not affected significantly by MIC-1. Studying the phenotype of DCs after MIC-1 exposure by FACS analysis, we observed that MIC-1 suppresses the expression of typical maturation molecules such as CD25 and CD83 as well as of CD86 during cytokine-induced DC maturation similar to Dex. In addition, T-cell stimulatory capacity of DCs was significantly reduced after MIC-1 exposure. MIC-1 was also able to increase slightly the expression of IDO (a key immunomodulatory enzyme promoting periphereal tolerance) in maturing DCs. conclusions: We have identified MIC-1 as a novel factor (secreted by decidual cells in early pregnancy) that could promote the increase of a tolerogenic subtype of DC in decidua.
57 citations
TL;DR: The potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states is demonstrated and non-decidualized factors may induce a pro-inflammatory cascade.
Abstract: Inadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the 'extravillous trophoblast' (EVT) invade through the differentiated uterine endometrium (the decidua) to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10(-8) M), medroxyprogesterone acetate (10(-7) M) and cAMP (0.5 mM) for 14 days. Conditioned media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM) of treatment. Isolated primary EVT cultured on Matrigel™ were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1 (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro-inflammatory condition. Overall, we have demonstrated the potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states.
55 citations
TL;DR: The present results reveal that abnormal protein profiles associated with OS induced ER stress and malfunction of UPR might be involved in the development of EPL, and OS and ER stress are potential targets for pregnant care and prognosis in normal pregnancy and its disorders.
Abstract: Early pregnancy loss (EPL) is one of the most common complications of human reproduction. Combined with our previous proteomic studies on villous and decidual tissues of EPL, we found that alterations of the proteins involved in oxidative stress (OS), unfolded protein response (UPR) and proteolysis presented a complex and dynamic interaction at the maternal-fetal interface. In the present study, we developed a cell model of OS using normal decidual cells to examine cell viability and expression levels of proteins related to endoplasmic reticulum stress (ER stress) and UPR. We found that glucose regulated protein 78 (GRP 78) and ubiquitinated proteins were significantly up-regulated in hydrogen peroxide (H2O2) treated decidual cells in a dose-dependent manner. Excessive OS could influence proper function of UPR by decreasing VCP in decidual cells, thereby leading to cell damage as well as inhibition of cell growth and activation of apoptosis. Furthermore, when pretreated with MG 132, a pharmacological inhibition of the proteasome, the H2O2 treated decidual cells became less viable and could not up-regulate the expression level of GRP 78 to resolve the protein-folding defects, which indicating that malfunction of UPR in decidual cells might aggravate the inhibitory effect of OS in decidual cells. The present results reveal that abnormal protein profiles associated with OS induced ER stress and malfunction of UPR might be involved in the development of EPL, and OS and ER stress are potential targets for pregnant care and prognosis in normal pregnancy and its disorders.
51 citations
TL;DR: Pro-inflammatory cytokines increases synthesis of M-CSF in first trimester decidual cells and activates macrophages, which initiate caspase-dependent EVT apoptosis.
46 citations
TL;DR: It is concluded that GATA2 is expressed during critical phases of early pregnancy, similar to that of the PR, and that it may play a major role in mediating P4 signaling in the mouse uterus.
42 citations
TL;DR: In this paper, the authors showed that reduced reproductive-tract progesterone receptor (PR) initiates labor, suggesting that reducing reproductive-to-ract PR is associated with abruption-associated preterm delivery.
Abstract: Plasma progesterone levels remain elevated throughout human pregnancy, suggesting that reduced reproductive-tract progesterone receptor (PR) initiates labor Placental abruption and excess thrombin generation elicit preterm delivery (PTD) PR, glucocorticoid receptor (GR), and total and p-ERK1/2 in decidual cells (DCs) and interstitial trophoblasts (IT) were assessed via immunohistochemical staining in abruption-associated PTD versus gestational-age matched control placentas, and in cultured DCs incubated with estradiol (E2) ± medroxyprogesterone acetate (MPA) ± thrombin Immunostaining for PR was lower in DC nuclei in abruption versus control decidua and was absent from ITs; GR was higher in IT than DCs, with no abruption-related changes in either cell type; p-ERK1/2 was higher in DCs in abruption than control decidua, with total ERK 1/2 unchanged Immunoblotting of cultured DCs demonstrated strong E2, weak MPA, and intermediate E2+MPA mediated elevation of PR-A and PR-B levels, with constitutive GR expression In cultured DCs, thrombin inhibited PR but not GR mRNA levels, reduced PR binding to DNA and [3H]progesterone binding to PR, and enhanced phosphorylated but not total ERK1/2 levels Coincubation with a specific p-ERK1/2 inhibitor reversed thrombin-enhanced p-ERK1/2 and lowered PR levels Thus, abruption-associated PTD is initiated by functional progesterone withdrawal, as indicated by significantly reduced DC nuclear expression of PR-A and PR-B Functional withdrawal of progesterone results in increased p-ERK1/2, and is thus one pathway initiating abruption-associated PTD
TL;DR: Results suggest that uterine DNM plays a major role for successful decidualization and embryo development during early pregnancy.
Abstract: Embryo-uterine interaction during early pregnancy critically depends on the coordinated expression of numerous genes at the site of implantation. The epigenetic mechanism through DNA methylation (DNM) plays a major role in the control of gene expression, although this regulatory event remains unknown in uterine implantation sites. Our analysis revealed the presence of DNA methyltransferase 1 (Dnmt1) in mouse endometrial cells on the receptive d 4 of pregnancy and early postattachment (d 5) phase, whereas Dnmt3a had lower abundant expression. Both Dnmt1 and Dnmt3a were coordinately expressed in decidual cells on d 6-8. 5-Methycytosine showed a similar expression pattern to that of Dnmt1. The preimplantation inhibition of DNM by 5-aza-2'-deoxycytodine was not antagonistic for embryonic attachment, although endometrial stromal cell proliferation at the site of implantation was down-regulated, indicating a disturbance with the postattachment decidualization event. Indeed, the peri- or postimplantation inhibition of DNM caused significant abrogation of decidualization, with concomitant loss of embryos. We next identified decidual genes undergoing alteration of DNM using methylation-sensitive restriction fingerprinting. One such gene, Chromobox homolog 4, an epigenetic regulator in the polycomb group protein family, exhibited hypomethylation in promoter DNA and increased expression with the onset of decidualization. Furthermore, inhibition of DNM resulted in enhanced expression of hypermethylated genes (Bcl3 and Slc16a3) in the decidual bed as compared with control, indicating aberration of gene expression may be associated with DNM-inhibition-induced decidual perturbation. Overall, these results suggest that uterine DNM plays a major role for successful decidualization and embryo development during early pregnancy.
TL;DR: The mechanisms involved in polyploidy cell formation in normal developmental processes are reviewed, with focus on known regulatory aspects in decidual cells.
Abstract: Polyploidy has been reported in several animal cells, as well as within humans; however the mechanism of developmental regulation of this process remains poorly understood. Polyploidy occurs in normal biologic processes as well as in pathologic states. Decidual polyploid cells are terminally differentiated cells with a critical role in continued uterine development during embryo implantation and growth. Here we review the mechanisms involved in polyploidy cell formation in normal developmental processes, with focus on known regulatory aspects in decidual cells.
TL;DR: Toll‐like receptor‐4 (TLR‐4) protects against Gram‐negative bacteria expressed lipopolysaccharide and ‘danger signals’ from injured or dying cells.
Abstract: Problem
Toll receptor-4 (TLR-4) protects against gram-negative bacteria expressed lipopolysaccharide and “danger signals” from injured or dying cells. Although decidual cells (DCs) and interstitial trophoblasts (ITs) are in close contact, TLR-4 has been studied extensively only in ITs.
TL;DR: FRA-1, induced in response to estrogen signaling via ESR1, is a key regulator of stromal differentiation and remodeling during early pregnancy, and controls the expression of matrix metalloproteinases MMP9 and MMP13, which are critical modulators ofStromal extracellular matrix remodeling.
TL;DR: Almost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure.
Abstract: Objective To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection. Methods Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E(2) (PGE(2)) was measured by enzyme immunoassay. Results Subclinical infection was confirmed in 10 women (28.5%). Microorganisms isolated were Ureaplasma urealyticum (4), group B streptococci (3), Gardnerella vaginalis (1), and Escherichia coli (2). We found a significant increase of pro-inflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE(2) was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages. Conclusions Almost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure.
TL;DR: The results of this study reveal that uNK cells likely do not play a major role in decidualization and accompanying angiogenesis during implantation, and identifies a large number of genes whose expression in implantation-site uterine tissue during decidUALization depends on interleukin-15 expression in mice.
Abstract: During decidualization, uterine natural killer (uNK) cells are the most abundant immune cell types found in the uterus. Although it is well known that they play key roles in spiral arteriole modification and the maintenance of decidual integrity seen after mid-pregnancy, their roles in the differentiation of decidual cells and accompanying angiogenesis during the process of decidualization is less well characterized. To address this, we used whole-genome Illumina BeadChip analysis to compare the gene expression profiles in implantation segments of the uterus during decidualization on day 7.5 of pregnancy between wild-type and uNK cell-deficient (interleukin-15-knockout) mice. We found almost 300 differentially expressed genes and verified the differential expression of ~60 using quantitative RT-PCR. Notably, there was a lack of differential expression of genes involved in decidualization and angiogenesis and this was also verified by quantitative RT-PCR. Similar endothelial cell densities and proliferation indices were also found in the endometrium between the implantation site tissues of wild-type and knockout mice undergoing decidualization. Overall, the results of this study reveal that uNK cells likely do not play a major role in decidualization and accompanying angiogenesis during implantation. In addition, the study identifies a large number of genes whose expression in implantation-site uterine tissue during decidualization depends on interleukin-15 expression in mice.
TL;DR: Findings provide evidence for an important role of Smad3 in decidualization and suggest that Smad2 and Smad 3 may have redundant roles in decdualization.
Abstract: Transforming growth factor (TGF)-β and activin, members of TGF-β superfamily, are abundantly expressed in the endometrium and regulate decidualization of endometrial stroma. Smad2 and Smad3 are receptor-regulated Smads (R-Smads) that transduce extracellular TGF-β/activin/Nodal signaling. In situ hybridization results showed that Smad3 was highly expressed in the decidual zone during the peri-implantation period in mice. By using artificial decidualization, we found that Smad3 null mice showed partially compromised decidualization. We therefore hypothesized that Smad2 might compensate for the function of Smad3 during the process of decidualization. Smad2 was also highly expressed in the decidual zone and phosphorylated Smad2 was much more abundantly increased in the deciduoma of Smad3 null mice than for wild-type (WT) mice. We further employed an in vitro uterine stromal cell decidualization model, and found that decidual prolactin-related protein (dPRP) and cyclin D3, which are well-known markers for decidual cells, were significantly down-regulated in Smad3 null decidual cells, and were much more significantly reduced when the expression of Smad2 was simultaneously silenced by its siRNA (P < 0.05). However, the expression levels of dPRP and cyclin D3 remained the same when Smad2 was silenced in WT decidual cells. Collectively, these findings provide evidence for an important role of Smad3 in decidualization and suggest that Smad2 and Smad3 may have redundant roles in decidualization.
TL;DR: The novel observation that TLR4 may play a much more important role in early-onset PE is demonstrated, and the spatial expression of Tollip at different stages of gestation may play an importantrole in the pathophysiology of PE.
Abstract: Objective. Toll-like receptor 4 (TLR4) is a key component of the innate arm of the immune system that mediates inflammatory responses following exposure to bacterial lipopolysaccharides. In doing so, TLR4 may contribute to the pathogenesis of preeclampsia (PE). We sought to assess the spatio-temporal expression of TLR4 and its negative regulator Toll-interacting protein (Tollip) in placental tissues from normal and preeclamptic pregnancies. Methods. Using immunohistochemistry and immunoblotting, we investigated the localization of TLR4 and its negative regulator Tollip in first- and third-trimester human placenta. Results. TLR4 was found to be expressed in the cytoplasm of trophoblasts in both first- (n = 6) and third-trimester (n = 24) placental villous samples. Tollip was mainly located in the cytoplasm of cytotrophoblasts in the first-trimester placental tissues; in contrast, our analyses of third-trimester placental tissues demonstrated that Tollip was mainly located in the decidual cells. Using weste...
TL;DR: The expression of galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, was significantly down-regulated in both Fkbp52 (-/-) and Pgr(-/-) uteri compared with WT uteri, suggesting that uterine Gal1 is an important downstream target of P(4)-FKBP52-PR signaling in the uterus to support P( 4) responsiveness during pregnancy.
Abstract: Progesterone (P4) signaling is critical for pregnancy. We previously showed that immunopilin FK506 binding protein (FKBP)52 serves as a cochaperone to optimize progesterone receptor (PR) function in the uterus, and its deficiency leads to P4 resistance in a pregnancy stage-specific and genetic background-dependent manner in mice. In particular, sc placement of SILASTIC implants carrying P4 rescued implantation failure in CD1 Fkbp52−/− mice, but the resorption rate was substantially high at midgestation due to reduced P4 responsiveness. Because downstream targets of P4-FKBP52-PR signaling in the uterus to support pregnancy are not clearly understood, we performed proteomic analysis using Fkbp52−/−, PR-deficient (Pgr−/−), and wild-type (WT) uteri. We found that the expression of galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, was significantly down-regulated in both Fkbp52−/− and Pgr−/− uteri compared with WT uteri. During early gestation, Lgals1, which encodes Gal1, was distinctly expressed in stromal and decidual cells. Lgals1 expression was much lower in d 4 Fkbp52−/− uteri compared with WT uteri, and this reduction was reversed by P4 supplementation. More interestingly, concomitant supplementation of recombinant Gal1 significantly suppressed the high resorption rate and leukocyte infiltration at implantation sites in CD1 Fkbp52−/− females carrying P4 SILASTIC implants. These findings suggest that uterine Gal1 is an important downstream target of P4-FKBP52-PR signaling in the uterus to support P4 responsiveness during pregnancy.
TL;DR: Both LMWHs induced a significant increase inDecidual HB-EGF expression/secretion and reduced TNF-α-induced decidual apoptosis and Tinzaparin demonstrated higher efficacy.
TL;DR: It is concluded that removing MUC1 from decidual tissue might help control trophoblast invasion by NK cells and support the alternative activation of tissue-specific CD14(+) cells and regulate their content of cytotoxic mediators.
TL;DR: Results show differential localization, protein expression and enzymatic activation of MMPs, suggesting specific roles for M MP-2 and MMP-9 in decidual and trophoblast tissues related to organogenic ECM remodeling and vascularization during early establishment of mouse placentation.
Abstract: During early placentation, matrix metalloproteinases (MMPs) play important roles in decidualization, trophoblast migration, invasion, angiogenesis, vascularization and extracellular matrix (ECM) remodeling of the endometrium. The aim of our study was to analyze the localization, distribution and differential expression of MMP-2 and -9 in the organogenic implantation site and to evaluate in vivo and in vitro decidual MMP-2 and -9 activities on day 10 of gestation in CF-1 mouse. Whole extracts for Western blotting of organogenic E10-decidua expressed MMP-2 and -9 isoforms. MMP-2 immunoreactivity was found in a granular and discrete pattern in ECM of mesometrial decidua (MD) near maternal blood vessels and slightly in non-decidualized endometrium (NDE). Immunoexpression of MMP-9 was also detected in NDE, in cytoplasm of decidual cells and ECM of vascular MD, in trophoblastic area and in growing antimesometrial deciduum. Gelatin zymography showed that MMP-9 activity was significantly lower in CM compared to the active form of direct (not cultured) and cultured decidua. The decidual active MMP-9 was significantly higher than the active MMP-2. These results show differential localization, protein expression and enzymatic activation of MMPs, suggesting specific roles for MMP-2 and MMP-9 in decidual and trophoblast tissues related to organogenic ECM remodeling and vascularization during early establishment of mouse placentation.
TL;DR: It is demonstrated that Amot, Amotl1, andAmotl2 were differentially expressed in uterine cells during the peri-implantation period, and that their expressions wereDifferentially regulated by P(4) and E(2).
Abstract: Increased vascular permeability and angiogenesis are hallmarks of the implantation process in the uterus Angiomotin (Amot), which is a vascular angiogenesis-related protein, belongs to the motin family There are two other members of the motin family, angiomotin-like 1 and 2 (Amotl1 and 2), which are also thought to be involved with angiogenesis In the present study, the distribution of motin mRNAs in the mouse uterus during the peri-implantation period was investigated by in situ hybridization Amot and Amotl1 were expressed in the stromal cells on days 3 and 4; expressions of Amotl2 during the same period were low During the postimplantation period, Amot and Amotl1 were expressed in secondary decidual cells, while Amotl2 expression fell to an undetectable level We also examined hormonal regulation of motin expression by steroid hormone treatment in ovariectomized mice We found that expression of Amot was induced by P(4) in stromal cells Additionally, Amotl1 expression was upregulated by both P(4) and estrogen (E(2)) in stromal cells, whereas E(2) increased this gene expression for only a limited time; after 12 h, expression dissipated In contrast, P(4) regulated the expression of Amotl2 in stromal cells, while E(2) regulated its expression in luminal epithelium cells Our results demonstrated that Amot, Amotl1, and Amotl2 were differentially expressed in uterine cells during the peri-implantation period, and that their expressions were differentially regulated by P(4) and E(2)
TL;DR: The immunohistochemical expression of TIMP1 and TIMP2 between an uncontrollably invasive phenomenon (cancer) and an “in situ” process (trophoblast invasion) was compared in an effort to assess any differential role of these molecules between these two distinct phenomena and therefore to understand better their contribution in cancer invasion and migration.
Abstract: Tissue inhibitors of metalloproteinases (TIMPs) play an important role in extracellular matrix homeostasis by regulating MMP activity. Although they were initially considered inhibitors of tumor growth and metastasis, recently their role in cancer progression has been controversial. The aim of our study was to compare the immunohistochemical expression of TIMP1 and TIMP2 between an uncontrollably invasive phenomenon (cancer) and an “in situ” process (trophoblast invasion) in an effort to assess any differential role of these molecules between these two distinct phenomena and therefore to understand better their contribution in cancer invasion and migration. We performed an immunohistochemical analysis of 50 carcinomas (colorectal, gastric, breast, pulmonary, and renal) and 40 first trimester gestations. The marker expression was evaluated semiquantitatively, separately in cancer parenchymal and trophoblastic cells as well as in malignant stromal and decidual cells, according to a percentage scale (0, 50%) and according to staining intensity (0, +, ++, and +++). Our results showed that there was no statistically significant difference in TIMP1 expression between cancer parenchymal cells and trophoblastic cells. On the other hand, TIMP1 was expressed more often in decidual cells than in cancer stromal cells. Immunostaining for TIMP2 was more extensive and intense both in trophoblastic and decidual cells than in cancer parenchymal and stromal cells, respectively. The reduced expression of TIMP2 in metastatic carcinomas by comparison with non-metastatic gestation specimens underlines its importance in cancer invasion and migration. On the other hand, TIMP1 was more expressed in decidua than cancer stroma, but at the same time showed no statistically significant difference between cancer parenchyma and trophoblasts, highlighting its multifunctional activity in cancer progression.
TL;DR: The use of VPA and OXC has a negative effect on the expression of extracellular matrix proteins that play a key role in embryo implantation in young rats, which may lead to pregnancies ending in failure.
TL;DR: Novel, preliminary findings provide insight into possible mechanisms via which the host inflammatory response could contribute to preterm birth and warrant further investigation in preterm samples.
TL;DR: RCAS1 staining may provide information regarding the intensity of the immunosuppressive microenvironment of both the molar lesion and the endometrium that can prove significant in determining the clinical course of hydatidiform mole.
Abstract: Introduction: Trophoblast cells cooperate with both maternal immune cells and decidual cells to help develop the suppressive microenvironment of the endometrium. The maternal immune
TL;DR: The results showed that IL1R2 gene expression was mainly localized in decidual cells close to the implanting embryo during days 5 to 8 of pregnancy, and under in vivo and in vitro artificialDecidualization, Il1r2 was significantly upregulated.
Abstract: Interleukin 1 (IL-1) is one of the most potent proinflammatory cytokines possessing a wide spectrum of inflammatory, metabolic, hemopoietic, and immunologic properties. In addition, the IL-1 system has been considered relevant in regulating communication between the blastocyst and the endometrium. Interleukin 1 receptor type II (IL1R2) acts as a negative regulator for IL-1 actions and has been termed a “decoy receptor.” The aim of this study was to determine the expression pattern of IL1R2 gene in mouse uterus during the early pregnancy. Both in situ hybridization and immunohistochemistry were performed to examine the spatial localization of IL1R2 expression in mouse uteri. Real-time quantitative polymerase chain reaction analyses were used to quantify Il1r2 messenger RNA (mRNA) level under in vivo and in vitro artificial decidualization. By transfecting Il1r2 gene in cultured stromal cells from day 4 pregnant mice, we detected the expression of Dtprp, a well-known marker for decidualization. Our results showed that IL1R2 gene expression was mainly localized in decidual cells close to the implanting embryo during days 5 to 8 of pregnancy. Under in vivo and in vitro artificial decidualization, Il1r2 was significantly upregulated. Dtprp mRNA expression was also upregulated by Il1r2 overexpression. Our data suggest that IL1R2 may play an important role during mouse decidualization.
TL;DR: Ectoplacental cone induces resistance to apoptosis in high doses of interferon (IFN)‐γ‐treated decidual cells in patients with programmed cell death.
Abstract: Citation Borbely AU, Fontenele-Neto JD, Vidsiunas AK, Gomes SZ, Hoshida MS, de Oliveira SF, Bevilacqua E. Ectoplacental cone induces resistance to apoptosis in high doses of interferon (IFN)-γ-treated decidual cells. Am J Reprod Immunol 2012; 67: 73–83
Problem In this study, we explored the relationship between decidual cells (DC) and interferon (IFN)-γ, in the presence or absence of ectoplacental cone (EC) using a coculture system.
Method of study Decidual cells and EC were isolated from pregnant mice on gestation day 7.5. DCs were cultured for 48 hr and then treated with fresh EC. After characterization, they were treated with IFN-γ, and cell death was evaluated.
Results Interferon-γ drastically increased decidual apoptosis, which was partially reverted by the addition of EC to the IFN-γ-treated decidual culture. Moreover, the addition of EC to non-treated DC cultures was also capable of attenuating death rates.
Conclusion Resistance to apoptosis may be induced in DC by the EC. This suggests that EC may participate in the inhibition of IFN-γ-dependent apoptosis and, therefore, play important role for DC survival in a cytokine-enriched placental environment.