Correlation of the expression of heparanase and heparin-binding EGF-like growth factor in the implantation window of nonconceptual cycle endometrium

Although it was suggested that heparanase (HPSE) may affect implantation and pregnancy, so far there have been no wide-ranging studies on the expression of and possible disturbances in the interactions between HPSE, heparan sulfate (HS) and related growth factors, such as heparin-binding EGF-like growth factor (HB-EGF). The aim of this study was to evaluate whether the expression profile of both HPSE and HB-EGF can be associated with impaired reproduction in the endometrial implantation window, in the non-conception cycle. The study group consisted of 32 women with two or more unexplained, consecutive miscarriages, and 61 idiopathic infertility patients, while the control comprised of 22 women with normal reproductive potential. We compared the expression of HB-EGF and HPSE at the transcript (qPCR) and protein (Western Blot) levels in eutopic endometrium. Also assessed were correlations between both factors in the studied groups. In women with consecutive miscarriages we observed lower HPSE relative transcript (p = 0.003) and lower protein (p = 0.002) level compared with the control group. Level of the HB-EGF protein was decreased (p = 0.017). HPSE mRNA level was higher in idiopathic infertility (p = 0.003) compared with women with miscarriages. We found statistically significant correlations in both transcript and protein levels in all groups (p < 0.05). Our results allow the assumption of the existence of a process by which, in normal human endometrium, HB-EGF expression coincides with the synthesis of HPSE. As a result, the HB-EGF molecule can bind to the HS on the cell surface, enhancing its affinity to the receptor. Then, the release of growth factors associated with HS oligomers occurs that is catalyzed by HPSE. We suggest that one of the causes of unexplained miscarriages may result from the impaired expression of HPSE and HB-EGF

Complement inhibitory proteins expression in placentas of thrombophilic women

Factors controlling complement activation appear to exert a protective effect on pregnancy. This isparticularly important in women with thrombophilia. The aim of this study was to determine the transcript andprotein levels of complement decay-accelerating factor (DAF) and membrane cofactor protein (MCP) in theplacentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry stainingof inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Westernblot. We observed a higher transcript (p < 0.05) and protein (p < 0.001) levels of DAF and MCP in the placentasof thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblastmembranes, but the assessment of staining in all groups did not differ. The observed higher expression level ofproteins that control activation of complement control proteins is only seemingly contradictory to the changesobserved for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changesassociated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas isan effect of proinflammatory cytokines, which accompanies thrombophilia, is probable.Factors controlling complement activation appear to exert a protective effect on pregnancy. This isparticularly important in women with thrombophilia. The aim of this study was to determine the transcript andprotein levels of complement decay-accelerating factor (DAF) and membrane cofactor protein (MCP) in theplacentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry stainingof inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Westernblot. We observed a higher transcript (p < 0.05) and protein (p < 0.001) levels of DAF and MCP in the placentasof thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblastmembranes, but the assessment of staining in all groups did not differ. The observed higher expression level ofproteins that control activation of complement control proteins is only seemingly contradictory to the changesobserved for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changesassociated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas isan effect of proinflammatory cytokines, which accompanies thrombophilia, is probable

Incidence of hereditary thrombophilia in women with pregnancy loss in multi-center studies in Poland

Aim: The aim of this study was to estimate the prevalence of factor V Leiden and prothrombin gene G20210A mutation among women with pregnancy loss in Poland. Material and methods: we analyzed a group of 396 women (mean age of 30.4 (±4.6) years), who experienced at least one pregnancy loss. Patients were recruited from 6 academic centers (Poznań, Białystok, Lublin, Wrocław, Bydgoszcz, Gdańsk), and were divided into the following groups: 122 patients with 3 episodes of early recurrent pregnancy loss (group 1), 87 patients with late pregnancy loss (group 2) and 46 patients with intrauterine pregnancy loss (group 3). Patients who did not fulfill the above inclusion criteria were divided into additional groups. 50 healthy women (mean age of 29.2 (±4.5) years), having at least one child, constituted the control group. Factor V Leiden mutation and prothrombin G20210A gene mutation were examined in all 396 women with pregnancy loss and 50 controls. For molecular analysis peripheral blood was tested. Genome DNA isolation from lymphocyte was performed with commercial assay QIAampDNA Blood Mini Kit. Results: Among 396 women with unexplained loss of at least one pregnancy 36 (9.1%) were carriers of inherited thrombophilia. Factor V Leiden mutation was present in 29 women (7.3%), prothrombin gene mutation G20210A in 6 (1.5%) and in 1 (0.3%) patient both mutations were detected. No coagulation defects were found in the control group. Factor V Leiden mutations was the most common disorder (21.7%) in patients with intrauterine demise and was significantly higher than in the group of women with early recurrent and late losses,

Matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinases (TIMP-1) and transforming growth factor-β2 (TGF-β2) expression in eutopic endometrium of women with peritoneal endometriosis

Introduction The prevalence of endometriosis among reproductive age women is 7–17%; however, these figures reach 20–50% in patients suffering from infertility. Matrix metalloproteinases (MMPs) activity is thought to be particularly essential in the early phases of endometriosis development. Any changes in the equilibrium between MMPs activity and their tissue inhibitors (TIMPs) could be potentially harmful, promoting endometriosis development. The aim of this study was to investigate whether the MMP-2, MMP-9, TIMP-1 or TGF-B2 expression in eutopic endometrium from women with early endometriosis differ when compared with healthy subjects. The results were referred to the serum progesterone levels. Material and Methods Endometrial biopsy was taken from 42 patients (18 in the study group, 22 in thecontrol group) at the time of hysteroscopy for routine histology and for RT-PCR procedures. Comparison of the quantity of gene products was performed with a programme for densitometry and compared to GADPH product, which was a reference value. Results The obtained results did not reveal any statistical difference in endometrial expression of MMP-2, MMp-9, TIMP-1, and TGF-β2 or serum progesterone level between women with endometriosis and without visible signs of this illness. Conclusions Despite the lack of statistical differences, it was observed that both examined metalloproteinases expressed a tendency to higher gene expression in the eutopic endometrium of women with endometriosis. However, both TIMP-1 and TGF-β2 expressions had the same tendency – higher values in endometriosis patients

Complement inhibitory proteins expression in placentas of thrombophilic women Complement inhibitory proteins expression in placentas of thrombophilic women

Factors controlling complement activation appear to exert a protective effect on pregnancy. This is&lt;br /&gt;particularly important in women with thrombophilia. The aim of this study was to determine the transcript and&lt;br /&gt;protein levels of complement decay-accelerating factor (DAF) and membrane cofactor protein (MCP) in the&lt;br /&gt;placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry staining&lt;br /&gt;of inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.&lt;br /&gt;Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.&lt;br /&gt;The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Western&lt;br /&gt;blot. We observed a higher transcript (p &amp;lt; 0.05) and protein (p &amp;lt; 0.001) levels of DAF and MCP in the placentas&lt;br /&gt;of thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblast&lt;br /&gt;membranes, but the assessment of staining in all groups did not differ. The observed higher expression level of&lt;br /&gt;proteins that control activation of complement control proteins is only seemingly contradictory to the changes&lt;br /&gt;observed for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changes&lt;br /&gt;associated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas is&lt;br /&gt;an effect of proinflammatory cytokines, which accompanies thrombophilia, is probable.<br>Factors controlling complement activation appear to exert a protective effect on pregnancy. This is&lt;br /&gt;particularly important in women with thrombophilia. The aim of this study was to determine the transcript and&lt;br /&gt;protein levels of complement decay-accelerating factor (DAF) and membrane cofactor protein (MCP) in the&lt;br /&gt;placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry staining&lt;br /&gt;of inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.&lt;br /&gt;Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.&lt;br /&gt;The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Western&lt;br /&gt;blot. We observed a higher transcript (p &amp;lt; 0.05) and protein (p &amp;lt; 0.001) levels of DAF and MCP in the placentas&lt;br /&gt;of thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblast&lt;br /&gt;membranes, but the assessment of staining in all groups did not differ. The observed higher expression level of&lt;br /&gt;proteins that control activation of complement control proteins is only seemingly contradictory to the changes&lt;br /&gt;observed for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changes&lt;br /&gt;associated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas is&lt;br /&gt;an effect of proinflammatory cytokines, which accompanies thrombophilia, is probable

Galectin-1 and Galectin-9 Concentration in Maternal Serum: Implications in Pregnancies Complicated with Preterm Prelabor Rupture of Membranes

Preterm prelabor rupture of membranes (pPROM) accounts for nearly half of premature births. Although several risk factors have been identified, no markers allowing for effective prevention have been discovered. In this study, we investigated how the maternal serum levels of galectin-1 and galectin-9 change in patients with pPROM in comparison to uncomplicated pregnancies. A total of 75 patients were enrolled to both study and control group (37 vs. 38, respectively). The serum concentration of galectin-1 and galectin-9 were assayed in duplicate using an enzyme-linked immunoassay. All analyses were performed using PQ Stat v. 1.8.4 software. Galectin-1 levels were significantly higher in the controls (13.32 vs. 14.71 ng/mL, p = 0.02). Galectin-9 levels were similar in both groups (13.31 vs. 14.76 ng/mL, p = 0.30). Lower galectin levels were detected for early pPROM (before 32nd GW) in comparison to late pPROM and the controls (8.85 vs. 14.45 vs. 14.71 ng/mL, p = 0.0004). Similar trend was observed in galectin-9 levels, although no statistical significance was found (11.57 vs. 14.25 vs. 14.76 ng/mL, p = 0.26). Low galectin-1 maternal serum level is associated with the incidence of preterm prelabor rupture of membranes. Galectin-9 maternal serum levels were not significantly correlated with pPROM. However, in order to investigate gal-1 and gal-9 levels as potential, promising markers of pPROM, further clinical studies on larger groups are required