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Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. We hypothesize that the success of the treatment is impaired by the presence of the immunosuppressive pregnancy-associated glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties. NSCLC-derived glycodelin interacts with immune cells in vitro and regulates the expression of genes associated with inflammatory and tumor microenvironment pathways. In tumor microarray samples of patients, high glycodelin staining in tumor areas results in an impaired overall survival of female patients. Moreover, glycodelin colocalizes to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. High serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. In summary, our findings suggest that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer. [ABSTRACT FROM AUTHOR]

Glycodelin (Gd) has pronounced immunomodulatory properties and participates in the development of immune tolerance during pregnancy. The role of recombinant Gd in physiological (0.2 and 2 μg/mL) and superphysiological (10 μg/mL) concentrations in the regulation of differentiation and functional activity of human myeloid-derived suppressor cells (MDSCs) was investigated in vitro. MDSCs were obtained from peripheral blood CD11b+ cells of healthy donors by two-step induction (IL-1β + granulocyte–monocyte colony-stimulating factor (GM-CSF) and lipopolysaccharide). The effect of Gd on the level of polymorphonuclear MDSCs (PMN-MDSCs) and monocyte MDSCs (M-MDSCs) was assessed. The intracellular level of indoleamine 2,3-dioxygenase (IDO) and arginase 1 (Arg1), as well as the cytokine profile in cultures of these cells, was measured. In general, the conversion of CD11b+ cells into MDSCs has the following features: as a result of cytokine induction, predominantly M-MDSCs are generated, but not PMN-MDSCs, and the level of Arg1 is practically not detected. It was found that Gd increased the number of M-MDSCs at concentrations of 2 and 10 μg/mL. It was shown that Gd did not affect the content of Arg1, but increased the number of MDSCs expressing IDO (10 μg/mL). Gd also modulated the cytokine profile of CD11b+ cells (at a physiological concentration of 2 μg/mL), suppressing IL-19, IL-26, and TWEAK/TNFsF12 production and, at a supraphysiological concentration, the production of IFN-α2 and IL-26. [ABSTRACT FROM AUTHOR]

An endometrial polyp is most commonly a benign, localized proliferation of the glands and the endometrial stroma, covered with epithelium and protruding above the level of the mucosa. These polyps are most often diagnosed during investigation into the causes of irregular menstrual bleeding or infertility. It is produced in the highest concentration during the secretory phase of the endometrial cycle. The level of glycodelin reaches its peak 12 days after ovulation. The aim of this paper was to determine the changes in the immunohistochemical expression of glycodelin at the level of the endometrium and in the tissue of the polyp, before and after hysteroscopic polypectomy, in infertile female patients with an endometrial polyp, and in the endometrial tissue of female patients without an endometrial polyp. The study included 82 infertile female patients. The infertile patients were divided into two groups. The first was the experimental group which included 56 infertile female patients who had an endometrial polyp. The second group was the control group, composed of 26 infertile female patients who did not have an endometrial polyp. The results obtained primarily indicate the existence of changes in the immunohistochemical expression of the cytokine glycodelin in the female patients from both the experimental and the control group, not only prior to but also after hysteroscopy. A larger number of patients who have an endometrial polyp show a lack of glycodelin expression, more pronouncedly so in the bioptate of the endometrium than in the endometrial polyp. [ABSTRACT FROM AUTHOR]

The incidence of chronic endometritis is particularly high in women with spontaneous abortions, especially habitual ones. There are insufficient data on the mechanisms of miscarriage in women whose pregnancy occurred along with this pathology. Aim: to assess the level of synthesis of cytokines and endometrial proteins in women with CE in the preconceptional stage and in the early stages of pregnancy; to identify pathogenetic aspects of the impact of imbalance of these substances on the processes of pregnancy loss; to assess the possibility of correcting the identified changes in the preconceptional stage. Materials and methods. The study was conducted in 2 phases. In the first phase, 426 women with CE were studied (168 patients (group I) were treated for CE in the preconception period, and the rest, 258 patients (group II), did not receive treatment). The control group consisted of 30 healthy women. The levels of cytokines TNF-a, INF-γ, and IL-10 in cervical mucus and glycodelin in menstrual blood were determined by enzyme-linked immunosorbent assay. In the second phase of the study, women who became pregnant were followed: 135 women from group I who received preconceptional treatment for CE; 168 women from group II who became pregnant along with untreated CE; and 20 healthy women from the control group who became pregnant and subsequently had no complications. At 5-6 weeks of gestation, serum glycodelin concentration and cervical content levels of TNF-a, INF-γ and IL-10 were determined. The data were processed using mathematical statistical methods, Student's t-test, Pearson's correlation coefficient (r) and odds ratio were evaluated using the STATISTICA program of StatSoft Inc. (USA). The study adhered to the tenets of the Declaration of Helsinki. The study protocol was approved by the local ethics committee of PSMU for all women enrolled in this study. The article is extracted from the initiative scientific research project of the Obstetrics and Gynecology Department No 2 of the Poltava State Medical University «Optimization of approaches to pregnancy management in women at high risk of obstetric and perinatal pathology» (term: 2022-2027; state registration number 0122U201228). Results and Discussion. At the preconceptional stage, patients with CE showed a significant decrease in glycodelin levels by 2.9 times (p<0.05), an increase in proinflammatory cytokines (INF-γ by 2.8 times (p<0.001), TNF-α by half (p<0.001)), and a decrease in IL-10 by 2 times (p<0.001) compared to the levels in healthy non-pregnant women. A decrease in the level of glycodelin in menstrual blood of women with CE is inversely correlated with an increase in the level of proinflammatory cytokines in cervical mucus (both INF-γ; r= -0.77; p<0.05, and TNF-α; r= -0.69; p<0.05). At 5-6 weeks of gestation, the level of serum glycodelin was 14.5 % lower (р˂0.05) in patients with pregestational untreated CE and 58.6 % lower (p<0.001) in women with early pregnancy loss. The level of this protein in menstrual blood of women with CE before pregnancy was positively correlated with its concentration in serum at 5-6 weeks of pregnancy (r=0.61; p<0.01). Such a relationship was also characteristic for INF-γ (r=0.68; p<0.05) and TNF-α (r=0.78; p<0.05). An inverse correlation was also found between a decrease in glycodelin levels in the blood of pregnant women with a history of untreated CE at 5-6 weeks of pregnancy and an increase in TNF-α (r= -0.63; p<0.05) and INF-γ (r= -0.57; p<0.05) in the cervical mucus of these pregnant women at this stage of pregnancy. After treatment for CE, both in the preconceptional stage and in early pregnancy, an increase in glycodelin (р˂0.001), a decrease in INF-γ (p<0.05) and TNF-α (p<0.01), and an increase in IL-10 concentration (р˃0.05) were observed. The incidence of spontaneous abortion before 22 weeks' gestation decreased 1.9-fold in women who received preconception treatment (OR 2.79; CI 95 % [1.45-5.38]; p < 0.05). Conclusions. In women with CE, there is a decrease in glycodelin synthesis and cytokine imbalance with an increase in proinflammatory cytokines: INF-γ (2.8-fold; р˃0.001) and TNF-α (twofold; p<0.001). The preconceptional decrease in glycodelin synthesis correlates with a decrease in synthesis of this protein by decidual cells after pregnancy, as well as with the prevalence of INF-γ and TNF-α in early pregnancy in women with a history of CE. This sets the stage for impaired immune tolerance between the uterus and the fetus and is one of the leading causes of spontaneous abortion in women who become pregnant with untreated CE. Preconceptional treatment of CE prevents the formation of cytokine imbalance and increases glycodelin synthesis in the early stages of pregnancy, which protects the course of pregnancy and reduces the incidence of early preterm labor by 4.6 times. [ABSTRACT FROM AUTHOR]

Pregnancy course depends on the appropriate connection between the mother and the developing foetus. Pregnancy is completed when the placenta is timely expelled. Placental retention is one of the possible pregnancy complications. Extracellular matrix, including adhesive proteins and enzymes that can break down collagens, seems to be responsible for it. The aim of the present study was to examine the impact of one of the adhesive proteins – glycodelin (Gd) – on selected metalloproteinases degrading collagens (MMP2, MMP3, MMP7). Placental tissues from healthy pregnant cows collected during early-mid pregnancy (2nd month n = 7, 3rd month n = 8, 4th month n = 6) and in cows that properly released placenta (NR; n = 6) and cows with retained foetal membranes (R; n = 6) were experimental material. The concentrations of glycodelin and protein content of selected metalloproteinases were measured by ELISA in the maternal and foetal placental homogenates as well as in the culture of epithelial cells derived from the maternal part of the placenta. The presence of these protein molecules was confirmed by Western Blotting. In the bovine placenta, the concentrations of examined proteins exhibit significant changes during placental formation. Gd, MMP3 and MMP7 concentrations decrease with pregnancy progress (between the 2nd and 4th month), while MMP2 concentrations were on the same level in this period. During parturition, concentrations of Gd and MMP3 were significantly higher in the R group compared to the NR group. In parallel, MMP2 concentrations did not show significant differences between the groups (NR vs R), and MMP7 concentrations decreased significantly in the maternal part of the placenta in cows with retained foetal membranes (R). Obtained results show correlations between the gestational age and proteins' (Gd, MMP3, MMP7) concentration, both in the maternal and foetal part of the placenta. • The presence of glycodelin protein was confirmed in bovine placenta. • The profiles of glycodelin and selected MMPs were described in bovine early pregnancy and parturition. • The alterations in glycodelin and selected MMPs might be related to retained foetal membranes. [ABSTRACT FROM AUTHOR]

The incidence of chronic endometritis is particularly high in women with spontaneous abortions, especially habitual ones. There are insuffi cient data on the mechanisms of miscarriage in women whose pregnancy occurred along with this pathology. Aim: to assess the level of synthesis of cytokines and endometrial proteins in women with CE in the preconceptional stage and in the early stages of pregnancy; to identify pathogenetic aspects of the impact of imbalance of these substances on the processes of pregnancy loss; to assess the possibility of correcting the identifi ed changes in the preconceptional stage. Materials and methods. The study was conducted in 2 phases. In the fi rst phase, 426 women with CE were studied (168 patients (group I) were treated for CE in the preconception period, and the rest, 258 patients (group II), did not receive treatment). The control group consisted of 30 healthy women. The levels of cytokines TNF-a, INF-γ, and IL-10 in cervical mucus and glycodelin in menstrual blood were determined by enzyme- linked immunosorbent assay. In the second phase of the study, women who became pregnant were followed: 135 women from group I who received preconceptional treatment for CE; 168 women from group II who became pregnant along with untreated CE; and 20 healthy women from the control group who became pregnant and subsequently had no complications. At 5-6 weeks of gestation, serum glycodelin concentration and cervical content levels of TNF-a, INF-γ and IL-10 were determined. The data were processed using mathematical statistical methods, Student’s t-test, Pearson’s correlation coeffi cient (r) and odds ratio were evaluated using the STATISTICA program of StatSoft Inc. (USA). The study adhered to the tenets of the Declaration of Helsinki. The study protocol was approved by the local ethics committee of PSMU for all women enrolled in this study. The article is extracted from the initiative scientifi c research project of the Obstetrics and Gynecology Department No 2 of the Poltava State Medical University «Optimization of approaches to pregnancy management in women at high risk of obstetric and perinatal pathology» (term: 2022-2027; state registration number 0122U201228). Results and Discussion. At the preconceptional stage, patients with CE showed a signifi cant decrease in glycodelin levels by 2.9 times (p

The amniotic variant of glycodelin (GdA) has pronounced immunomodulatory properties, being involved in the formation of immune tolerance during pregnancy. The effect of GdA on the amount of T-regulatory lymphocytes (Treg) and the level of acute phase proteins (α-2-macroglobulin (α-2M), orosomucoid, C-reactive protein (CRP)) were studied during the administration of allogeneic red bone marrow (BM) cells to Wistar rats in a dynamic in vivo experiment. It was established that the administration of GdA against the background of the administration of allogeneic BM caused an increase in the portion of peripheral Tregs among CD4+ lymphocytes at the end of the experiment (on the 21st day) as compared with the group, which received BM. It was demonstrated that GdA decreased the level of CRP and α-2M, but increased the orosomucoid concentration in the serum of experimental animals at the beginning of the experiment (third day); however, normalization of the content of acute phase proteins to the level of intact animals was observed by the end of the experiment (21st day) in all groups of experimental animals. Thus, glycodelin is able to realize an immunosuppressive effect relative to the allogeneic cells through an increase in the level of Treg and orosomucoid, as well as a decrease in the concentration of CRP and α-2M. [ABSTRACT FROM AUTHOR]

Glycodelins, the glycosylated proteins of reproductive tract are characterized by immunomodulatory functions, are of interest because of their role in the development of immune tolerance. Interleukin-17-producing T helpers (Th17) bearing the surface marker CCR6, are a heterogeneous cell population with increased plasticity and functional dichotomy. On the one hand, these cells support antimicrobial and antifungal immunity and microbiota composition; on the other hand, they are involved in the pathogenesis of autoimmune diseases, graft rejection, and pregnancy complications. Despite the scientific interest in glycodelin as an immunomodulator, its direct effects on pro-inflammatory Th17 have not been studied. Therefore, the aim of our work was to investigate the effect of recombinant human glycodelin on Th17 polarization of naïve human T helper cells cells by assessing surface expression of CCR6, CCR4, and CXCR3 molecules. Naïve T helper cells were polarized for 7 days in vitro to Th17 cells with a TCR activator and cytokines for 7 days, supplemented with glycodelin at concentrations appropriate for the 1st and 2nd trimesters of pregnancy. The percentages of CD4+CCR6+ cell population (Th17 cells), and their CCR4+CXCR3-(Th17/Th22) and CCR4-CXC3+ subpopulations (Th17.1) was then determined. Moreover, the levels of IL-17, IL-2, and other cytokines/chemokines were determined in the culture supernatants of Th17-polarized T helper cells. Treatment with recombinant glycodelin at concentrations equivalent to those in pregnancy (0.2, 2, and 10 μg/mL) did not alter the percentage of CD4+CCR6+ cells in culture, or their IL-17 production. However, at a concentration of 10 μg/mL, it caused a decrease in Th17.1 (CCR6+CCR4-CXCR3+) percentage in the T helper culture, and increased the production of IL-2. In addition, glycodelin was found to have selective pro-apoptotic activity against Th17.1 if applied at 2 μg/mL. Given the known involvement of these cells in pathological processes, the observed effect of glycodelin could be of interest from a biopharmaceutical perspective. However, the mechanism of the revealed selective effects of this pregnancy protein needs further investigation.

The effect of the intramural fibroids not distorting the cavity remains controversial on implantation and pregnancy. The aim of this study was to examine the impact of non-cavity distorting intramural fibroids on endometrium. Fifty-six women with non-cavity distorting intramural fibroid were recruited in this study. Paired endometrial specimens, one from beneath the fibroid (ipsilateral endometrium) and the other from the opposite side of uterine cavity, away from the fibroid (contralateral endometrium) were obtained 7–9 days after the luteinizing hormone surge in a natural cycle. Histological dating, Mucin1 and Glycodelin expression and uterine natural killer (uNK) cell density were compared between the paired samples. The median (IQR) H-score of Mucin1 staining in the ipsilateral luminal epithelium was 210% (142–230%), which was significantly (p < 0.05) higher than that of the contralateral luminal endometrium (157%, IQR 114–176%). There was no significant difference in Mucin1 expression in the glandular epithelium. There was no significant difference in Glycodelin expression in luminal and glandular epithelium, uNK cells density or histological dating results between the paired endometrial samples. In conclusion, it is uncertain whether the altered expression of Mucin1 in luminal epithelium alone may have impact on implantation when other markers are not changed. [ABSTRACT FROM AUTHOR]

Objective of the study to analyze and summarize the available data on the role of glycodelin in carcinogenesis and its expression in various cancers.Material and Methods. A literature search was conducted in Medline, PubMed Central, NCBI databases in the time interval from January 1983 to October 2019 using the key words glycodelin and cancer. Of the 104 publications found, 21 were used to write the review.Results. This paper presents the overview of the findings in current research focusing on the properties of glycodelin, the major lipocalin protein of the human reproductive system. Some lipocalins are known to play a key role in cancer development as well as influence signaling pathways in the regulation of cell motility, differentiation and neovascularization. Most likely they can be used as cancer markers. Glycodelin A is determined in serum and, due to its special immunoregulatory properties, can serve as a useful prognostic marker and a promising target for future anti-cancer therapies. The presence of glycodelin A in breast cancer tissue is known to be mostly linked to a better prognosis than is attributed to glycodelin-negative tissue, as glycodelin is a protein typical of differentiated tissue. On the other hand, glycodelin might play a role in neovascularisation, thereby promoting tumor growth. Glycodelin is a biomarker of aggressive malignant pleural mesothelioma and a prognostic biomarker of metastatic non-small cell lung cancer at late stages. Glycodelin hyperexpression is associated with brain metastasis in lung adenocarcinoma, and its determination can be used as an additional prognostic factor.Conclusion. The review refects basic scientifc data and results of clinical trials, as well as identifes future prospects that allow the development of new methods for cancer detection and treatment. It should be noted that glycodelin plays an important role in tumor development, progression, angiogenesis, and the formation of distant metastases, and therefore can serve as a useful diagnostic and prognostic marker. Further studies of the functional properties of glycodelin are needed to develop promising strategies in cancer therapy.

Objective: Evaluation of glycodelin (Gd) concentrations in serum and cervico-vaginal secretions as a predictor for implantation after ICSI. Materials and methods: Prospective study on 50 women undergoing ICSI where long protocol ovarian stimulation was used. Serum and cervico-vaginal lavage Gd concentrations were measured then rates of biochemical and clinical pregnancy were detected and predictive value was evaluated using logistic regression analysis. Results: Using cut-off values of 2.2 ng/ml and 1.9 ng/ml for serum and cervico-vaginal Gd concentrations respectively for biochemical pregnancy and values of 2.7 ng/ml and 1.3 ng/ml respectively for clinical pregnancy, there was no significant difference regarding sensitivity (72% & 56%, and 72% & 89%, respectively and respectively). Specificity was statistically similar for biochemical pregnancy (72% and 89%, respectively) while specificity was significantly higher for clinical pregnancy using cervico-vaginal Gd concentration of 1.3 ng/ml (88%) compared to serum Gd concentration of 1.9 ng/ml (53%). Conclusion: Glycodelin appears to be a promising marker for implantation after IVF/ICSI.

Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. We hypothesize that the success of the treatment is impaired by the presence of the immunosuppressive pregnancy-associated glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties. NSCLC-derived glycodelin interacts with immune cells in vitro and regulates the expression of genes associated with inflammatory and tumor microenvironment pathways. In tumor microarray samples of patients, high glycodelin staining in tumor areas results in an impaired overall survival of female patients. Moreover, glycodelin colocalizes to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. High serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. In summary, our findings suggest that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glycodelin (PP14, PAEP, alpha-2-microglobulin, dimeric glycoprotein with molecular weight of 42 to 56 kDa) is considered as a reproductive tissue receptivity marker. Despite that glycodelin immunosuppressive effects are well-known there still remains uncovered its role in myeloid suppressor cell (MDSC) regulation. MDSC represent the heterogeneous population of immature myeloid cells that acquire suppressor phenotype while inhibiting the immune response under the pathological states. MDSC are known to play an essential role in supporting the immune tolerance in pregnancy and at transplantation. Our hypothesis suggests that glycodelin is capable of inducing the MDSC formation as the level of these cells is elevated during the successful pregnancy, whereas the spontaneous abortion and progression of eclampsia are associated with low circulating glycodelin. Therefore, the aim of the work was to analyze the role of recombinant glycodelin in physiological concentrations in regulation of MDSC differentiation. Peripheral blood mononuclear cells of donor volunteers were separated via centrifugation on density gradient of 1,077 g/cm3 (Ficoll-Hypaque, Sigma-Aldrich) to obtain MDSC generation in vitro. Then cells obtained were cultured in 24-well plate at a concentration of 1 × 106 cell/ml in complete medium with cytokines IL-6 (20 ng/ml), GM-CSF (40 ng/ml) therein for 14 days at 37 °C and 5% CO2. Medium replacement was made by 7th day in culture followed by cytokine re-introduction, and on the 11th day recombinant glycodelin in physiological concentrations (0,2; 2 mkg/ml) was applied while the pharmacological concentration was 50 mkg/ml. The M-MDSC (LinHLA-DRCD33+CD11b+CD14+CD66b- ) and PMN-MDSC (LinHLA-DRCD33+CD11b+CD14- CD66b+) level was evaluated in cultures using flow cytometry (СytoFlexS (Beckman Coulter)) and “R&D Systems” antibodies according to standard protocol. Statistical data processing was realized with GraphPad Prizm software using Friedman test. It was found that glycodelin did not significantly affect cell viability being assessed with flow cytometry (PI). It was revealed that high GdA concentration (50 mkg/ml) being pharmacological did not render significant effect on MDSC differentiation. Meanwhile, glycodelin in concentrations correspanding the healthy pregnancy (0,2; 2 mkg/ml) was stated to increase the MDSC percentage in induced cultures of human mononuclear cells. When analyzing the subsets it was disclosed that this effect was conditioned by the increase in PMN-MDSC level while the M-MDSC level remained significantly unchanged. This result could be interpreted as glycodelin fetoprotective effect as the increase of the PMN-MDSC level is associated with the suppression of the immune response to paternal antigens. The PMN-MDSC level is known to be elevated in peripheral blood of healthy pregnant women at all the stages of pregnancy as compared to nonpregnant subjects whereas the M-MDSC amount remains unaltered. Meanwhile, patients with miscarriage demonstrated more that by 30% lowering in the MDSC amount in blood and endometrium and in I trimester, in particular. During the physiological pregnancy PMN-MDSC accumulate in placenta, but at spontaneous abortion their number is found to be declined. Placental PMN-MDSC efficiently suppress the T-cell response while concurrently polarizing the CD4+ lymphocytes in Th2 phenotype. PMN-MDSC are suggested to play an essential role in inducing and supporting the tolerance to fetal antigens that allows considering these as promising target of therapeutical manipulation in pregnancy complications. As a whole, we have originally demonstrated the GdA effect on MDSC differentiation.

The protein glycodelin (PP14, PAEP) is associated with pregnancy and exhibits pronounced immunotropic properties. We studied the effect of glycodelin on the cytokine profile of blood serum during transplantation a suspension of allogeneic red bone marrow cells to Wistar rats. Recombinant glycodelin was administered to the animals 4 times (14 μg each time). Against the background of bone marrow cell transplantation, the levels of proinflammatory (IL-1α, IL-1β, and IL-18) and regulatory (IL-7, IL-12) cytokines and CSF (M-CSF) increased in blood serum, which indicates a systemic inflammatory response to the allograft. Glycodelin administration against the background of bone marrow cell allotransplantation led to a significant decrease in the proinflammatory cytokine IL-17A on day 21 of the experiment; the concentrations of the other cytokines remained unchanged. In general, glycodelin can suppress the level of IL-17A, a marker of graft rejection, which opens perspectives for its further investigation as a potential drug. [ABSTRACT FROM AUTHOR]

HIGHLIGHTS 1. Obesity increases the risk of comorbidities especially for the pregnancy. 2. The study analyzed glycodelin levels and uterine NK cell expression using Rattus norvegicus as animal model. 3. uNK cell expression of the obese rats group was higher as the marker of chronic inflammation for obesity. 4. Although there was increasing uNK cells in obese rats group, this result was not followed by the level of gycodelin. ABSTRACT Objectives: To prove the existence of differences in glycodelin levels and uterine NK cell expression in obese and non-obese female white rats of Wistar strain (Rattus norvegicus). Materials and Methods: . This study used a randomized post-test only controlled group design. This in vivo study used two groups of female rats (Rattus norvegicus). Group 1 was treated with the high obese diet for eight weeks, and group 2 was not treated with the high obese diet. After eight weeks, the rats were weighed, the proestrus phase was synchronized, and then the rats were terminated. Results: In this study, there was no significant difference in glycodelin levels between the obese and non-obese groups with a p= 0.821 (p >0.05). Significant differences were found in uterine NK cell expression between obese dan non-obese groups with p=0.001 (p

The aim of this study was to assess the correlation between uterine artery Doppler parameters examined from 20-24 weeks of pregnancy with glycoledin level in maternal blood. The study included 80 patients attending our clinic from September 2019 to June 2020. Participants were divided into two groups according to uterine artery findings. Group 1 included pregnant patients who had abnormal uterine artery Doppler USG at 2224 weeks of pregnancy, and Group 2 consisted of healthy pregnant patients with uterine artery Doppler USG performed during the same period of pregnancy. Serum glycodelin levels were analyzed at 24 weeks of gestation of two goups and their perinatal outcomes were compared. No significant difference were seen between the groups regarding age, body mass index, blood pressure, gestational age, and blood test sampling time for serum glycodelin analysis. The mean pulsatility index values detected with Doppler ultrasonography were 1.92±0.41 and 0.82±0.25 for Groups 1 and 2, respectively. Comparative analysis revealed that the mean glycodelin level was significantly higher in Group 1 than Group 2 (521.75±21.68 -475.67±41.09; p< 0.001). Glycoledin may assist in predicting negative perinatal outcomes especially preeclampsia. However, many more comperative studies with larger series from multicenter are need to support this conclusion. [Med-Science 2021; 10(2.000): 545-50]

Zexu Ni,1,* Lingling Zhang,2,3,* Jinhua Zheng,1 Xiaojie Su,1 Shucai Zhang2 1Department of Pathology, Dongguan Tungwah Hospital, Dongguan 523110, People’s Republic of China; 2Department of Oncology, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, People’s Republic of China; 3Department of Oncology, Peking University International Hospital, Beijing 102206, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shucai ZhangDepartment of Oncology, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, People’s Republic of ChinaEmail sczhang6304@163.comObjective: Brain metastasis (BM) is a serious complication of advanced lung adenocarcinoma and is a prominent factor leading to lung cancer mortality. In this study, the expression of the glycodelin protein was analyzed in EGFR-mutant tyrosine kinase inhibitor-sensitive advanced lung adenocarcinoma.Methods: This study features a retrospective analysis of 74 advanced lung adenocarcinoma patients treated at our hospital from January 2010 to December 2017. The expressions of glycodelin were assessed by standard immunohistochemistry and correlated with clinicopathological factors and overall survival (OS) outcomes.Results: Patients with advanced lung adenocarcinoma with glycodelin overexpression were prone to BM (P < 0.05), and exhibited significantly shortened OS (11.8 months vs 20.4 months, P < 0.05). Multivariate regression analysis showed that overexpression of glycodelin and brain metastases were independent factors affecting the prognosis of advanced lung adenocarcinoma (P < 0.05).Conclusion: The overexpression of glycodelin is closely related to the presence of brain metastasis in lung adenocarcinoma, and can be used as an auxiliary diagnostic index for prognosis of advanced lung adenocarcinoma.Keywords: glycodelin, advanced lung adenocarcinoma, brain metastasis, prognosis

The two lipocalins, β-lactoglobulin (βLg) and glycodelin (Gd), are possibly the most closely related members of the large and widely distributed lipocalin family, yet their functions appear to be substantially different. Indeed, the function of β-lactoglobulin, a major component of ruminant milk, is still unclear although neonatal nutrition is clearly important. On the other hand, glycodelin has several specific functions in reproduction conferred through distinct, tissue specific glycosylation of the polypeptide backbone. It is also associated with some cancer outcomes. The glycodelin gene, PAEP, reflecting one of its names, progestagen-associated endometrial protein, is expressed in many though not all primates, but the name has now also been adopted for the β-lactoglobulin gene (HGNC, www.genenames.org). After a general overview of the two proteins in the context of the lipocalin family, this review considers the properties of each in the light of their physiological functional significance, supplementing earlier reviews to include studies from the past decade. While the biological function of glycodelin is reasonably well defined, that of β-lactoglobulin remains elusive.

The aim of this study was to assess the correlation between uterine artery Doppler parameters examined from 20-24 weeks of pregnancy with glycoledin level in maternal blood. The study included 80 patients attending our clinic from September 2019 to June 2020. Participants were divided into two groups according to uterine artery findings. Group 1 included pregnant patients who had abnormal uterine artery Doppler USG at 22-24 weeks of pregnancy, and Group 2 consisted of healthy pregnant patients with uterine artery Doppler USG performed during the same period of pregnancy. Serum glycodelin levels were analyzed at 24 weeks of gestation of two goups and their perinatal outcomes were compared. No significant difference were seen between the groups regarding age, body mass index, blood pressure, gestational age, and blood test sampling time for serum glycodelin analysis. The mean pulsatility index values detected with Doppler ultrasonography were 1.92±0.41 and 0.82±0.25 for Groups 1 and 2, respectively. Comparative analysis revealed that the mean glycodelin level was significantly higher in Group 1 than Group 2 (521.75±21.68 -475.67±41.09; p< 0.001). Glycoledin may assist in predicting negative perinatal outcomes especially preeclampsia. However, many more comperative studies with larger series from multicenter are need to support this conclusion. [ABSTRACT FROM AUTHOR]

The two lipocalins, β-lactoglobulin (βLg) and glycodelin (Gd), are possibly the most closely related members of the large and widely distributed lipocalin family, yet their functions appear to be substantially different. Indeed, the function of β-lactoglobulin, a major component of ruminant milk, is still unclear although neonatal nutrition is clearly important. On the other hand, glycodelin has several specific functions in reproduction conferred through distinct, tissue specific glycosylation of the polypeptide backbone. It is also associated with some cancer outcomes. The glycodelin gene, PAEP , reflecting one of its names, progestagen-associated endometrial protein, is expressed in many though not all primates, but the name has now also been adopted for the β-lactoglobulin gene (HGNC, www.genenames.org). After a general overview of the two proteins in the context of the lipocalin family, this review considers the properties of each in the light of their physiological functional significance, supplementing earlier reviews to include studies from the past decade. While the biological function of glycodelin is reasonably well defined, that of β-lactoglobulin remains elusive. [ABSTRACT FROM AUTHOR]

Endometriosis is one of the important issues in women worldwide, which decreases the quality of women's lives in their reproductive age. The diagnosis of endometriosis is carried out by the invasive procedure, which is expensive and painful. In the last few decades, researchers have given more attention to constructing a suitable biomarker-based biosensor for semi/non-invasive diagnosis of endometriosis. As a result, glycodelin (GLY) was found as a promising biomarker because of its selectivity and sensitivity. To the best of our knowledge, it was the first study that reported the detection of GLY biomarker using an electrochemical immunosensor. Briefly, a label-free electrochemical immunosensing platform was constructed through in-situ surface modification of cysteamine layer and immobilisation of antibody (anti-GLY) with help of glutaraldehyde. The interaction between antigen and antibody was measured using square wave voltammetry (SWV). The SWV signal could decrease proportionally with the increasing GLY concentration ranging from 1 to 1000 ng mL−1 (R2 = 0.9981) and a detection limit (LOD) of 0.43 ng mL−1. Moreover, an immunosensor could exhibit high sensitivity, selectivity, long-term stability, reproducibility and regeneration. Accuracy of the immunosensor was compared with enzyme-linked immunosorbent assay (ELISA), and satisfying results were obtained. The detection of GLY biomarker may be a new possibility for endometriosis diagnosis. Schematic illustration of step by step fabrication of modified electrode and detection GLY. Image 1 • An electrochemical immunosensor for the detection of glycodelin biomarker in endometriosis is first time reported. • The LOD was 0.43 ng mL−1 and the liner domain 1–1000 ng mL−1. • In addition, the sensor exhibited acceptable selectivity, good storage stability, and high reproducibility. • The applicability of the fabricated sensor to actual human serum samples. • The proposed immunosensor is very promising for clinical applications for endometriosis. [ABSTRACT FROM AUTHOR]

A role for fibroblasts in physiological and pathological angiogenesis is now well recognized; however, the precise mechanisms underlying their action have not been determined. Using an in vitro angiogenesis model in combination with a candidate gene approach, column chromatography, and mass spectrometry, we identify two classes of fibroblast-derived factors--one that supports vessel sprouting but not lumen formation, and one that promotes lumen formation. In the absence of fibroblasts a combination of angiopoietin-1, angiogenin, hepatocyte growth factor, transforming growth factor-α, and tumor necrosis factor drives robust endothelial cell (EC) sprouting; however, lumens fail to form. Subsequent addition of fibroblast-conditioned medium restores lumenogenesis. Using small interfering RNA-mediated knockdown, we show that five genes expressed in fibroblasts--collagen I, procollagen C endopeptidase enhancer 1, secreted protein acidic and rich in cysteine, transforming growth factor-β-induced protein ig-h3, and insulin growth factor-binding protein 7--are necessary for lumen formation. Moreover, lumen formation can be rescued by addition of purified protein to knockdown cultures. Finally, using rheology, we demonstrate that the presence of these matricellular proteins results in significantly stiffer gels, which correlates with enhanced lumen formation. These findings highlight the critical role that fibroblast-derived extracellular matrix components play in EC lumen formation and provide potential insight into the role of fibroblasts in the tumor microenvironment.

Background Failure in the endometrial receptivity may account for a significant number of infertility cases including unexplained infertility in women. Reduction in the endometrial estrogen receptor-alpha (ER-α) expression during implantation may be a critical event that coincides with the expression of specific genes and the formation of a receptive endometrium. The aim of the present study was to assess the expression of ER-α in the mid-secretory phase in the endometrium of women with unexplained infertility. Materials and Methods This case-control study was carried out on randomly selected fertile (n=10) and infertile (n=16) women whose source of infertility remained unexplained. We evaluated the expression of ER-α and glycode-lin-A (GdA) through mRNA level measurement with real-time polymerase chain reaction (PCR) in the endometrium of fertile women and patients suffering from unexplained infertility and fertile women. Endometrial biopsies of each subject were collected during a single menstrual cycle 7 days after the peak of luteinizing hormone (LH+7). Results Endometrial expression level of ER-α was significantly (P < 0.05) higher in the patients with unexplained infertility compared to the control. Significantly (P < 0.05) lower levels of GdA expression were seen in women with unexplained infertility. A statistically non-significant negative correlation was observed between ER-α and GdA mRNA expression. Conclusion Our findings demonstrate that reduction in the endometrial GdA expression is associated with elevated expression of ER-α in mid-luteal phase. Disruption in the endometrial ER-α expression, which leads to defects in uterine receptivity, may contribute to unexplained infertility.

Background and Objectives: Inflammation and oxidative stress have been described to reduce the chance for pregnancy instauration and maintenance. NOFLAMOX, a recently developed herbal preparation with recognized antioxidant and anti-inflammatory properties, can represent an interesting treatment to increase the chance of pregnancy, both physiological or after in vitro fertilization (IVF). The aim of this study was to assess NOFLAMOX's effect; a population with unexplained infertility was screened for the recently described IMMUNOX panel based on four immunological biomarkers with a prospective study approach. Materials and Methods : Patients with unexplained infertility and positive for at least one of the biomarkers of the IMMUNOX panel were included in this study and treated with NOFLAMOX for three months prior to an IVF cycle. Results : Eighty-six patients ( n = 86) were screened with the IMMUNOX panel and the forty-seven (54.5%) found positive were included in this study. In more detail, 11 were positive for TNFα (23.4%), 18 (38.3%) for glycodelin (GLY), 29 (61.7%) for Total Oxidative Status (TOS), and 32 (68.1%) for Complement Activity Toxic Factor (CATF). After three months of treatment, a significant reduction in the number of IMMUNOX-positive patients was observable, with 26 patients who turned IMMUNOX-negative displaying a quantitative statistically significant variation of 100% (11/11), 38.9% (7/18), 65.5% (18/29), and 75% (24/32), for TNFα, glycodelin, TOS, and CATF, respectively. Followed in the subsequent IVF cycle, this NOFLAMOX-treated population showed a pregnancy rate of 42.3% compared to the 4.7% of the IMMUNOX-positive group of patients. Conclusions : Taken together, the results of this study suggest that NOFLAMOX could represent an interesting option for those patients with unexplained infertility of inflammatory/oxidative origin. Further studies are needed to confirm these results and explore possible strategies to restore fertility in women with immune-mediated sterility.

Study Question: Are there differences in the proteomic profile of exosomes isolated from seminal plasma of normozoospermic (NSP) and severe asthenozoospermic (SA) men, potentially contributing to sperm features?Summary Answer: A relevant group of proteins known to positively regulate sperm functions were over-represented in seminal exosomes of NSP men, i.e. cysteine-rich secretory protein-1 (CRISP1), while the inhibitory protein glycodelin was enriched in exosomes of SA subjects.What Is Known Already: Exosomes are secreted along the male reproductive tract and are thought to be involved in spermatozoa maturation and function. Ejaculated spermatozoa are still able to capture exosomes; exosomes of NSP individuals improve sperm motility and prompt capacitation, while exosomes of SA men fail to exert similar features.Study Design, Size, Duration: Semen samples from NSP and SA men, aged 18 to 55 and registered at a single IVF center, were considered for this study project. Subjects were subdivided into three groups: a discovery cohort (five NSP men and six SA patients), a validation cohort (seven NSP and seven SA men) and the 'glycodelin analysis' cohort (20 NSP and 37 SA men). Exosomes were purified from semen of every participant.Participants/materials, Setting, Methods: Exosomes were characterized by nanoparticle tracking analysis, transmission electron microscopy and western blot. Comprehensive proteomics analysis of the exosomal proteome was performed by nanoscale liquid chromatographic tandem mass spectrometry analysis. Funrich software was used to determine statistical enrichment of pathways, networks and Gene Ontology terms of the identified proteins. Validation of differentially expressed proteins was performed through ELISA and western blot analysis.Main Results and the Role Of Chance: The comprehensive proteomic analysis identified a total of 2138 proteins for both groups. There were 89 proteins found to be differentially expressed in exosomes of NSP versus SA subjects, of which 37 were increased in the NSP group and 52 were increased in the SA group. One-third of the exosomes-associated proteins highly expressed in NSP samples were involved in the reproductive process; conversely, the over-expressed proteins in exosomes of SA samples were not functionally specific. Quantitative data were confirmed on seminal exosomes from different cohorts of subjects.Large Scale Data: N/A.Limitations, Reasons For Caution: Transfer of the proteins from exosomes to spermatozoa has been only partially demonstrated and up-take mechanisms are still poorly defined.Wider Implications Of the Findings: Seminal exosomes carry proteins that are potentially able to either favour or inhibit the reproductive process in humans. A better understanding of these phenomena might pave the way for novel intervention measures in terms of male infertility.Study Funding/competing Interest(s): This study was funded by the Italian Ministry of Health through an Institution Seed Grant. None of the authors has any competing interests. [ABSTRACT FROM AUTHOR]

Study Question: Does glycodelin-A (GdA) induce conversion of human peripheral blood CD16-CD56bright natural killer (NK) cells to decidual NK (dNK) cells to facilitate placentation?Summary Answer: GdA binds to blood CD16-CD56bright NK cells via its sialylated glycans and converts them to a dNK-like cells, which in turn regulate endothelial cell angiogenesis and trophoblast invasion via vascular endothelial growth factor (VEGF) and insulin-like growth factor-binding protein 1 (IGFBP-1) secretion, respectively.What Is Known Already: dNK cells are the most abundant leucocyte population in the decidua. These cells express CD16-CD56bright phenotype. Peripheral blood CD16-CD56bright NK cells and hematopoietic precursors have been suggested to be capable of differentiating towards dNK cells upon exposure to the decidual microenvironment. These cells regulate trophoblast invasion during spiral arteries remodelling and mediate homoeostasis and functions of the endothelial cells. GdA is an abundant glycoprotein in the human decidua with peak expression between the 6th and 12th week of gestation, suggesting a role in early pregnancy. Indeed, GdA interacts with and modulates functions and differentiation of trophoblast and immune cells in the human feto-maternal interface. Aberrant GdA expression during pregnancy is associated with unexplained infertility, pregnancy loss and pre-eclampsia.Study Design, Size, Duration: CD16+CD56dim, CD16-CD56bright and dNK cells were isolated from human peripheral blood and decidua tissue, respectively, by immuno-magnetic beads or fluorescence-activated cell sorting. Human extravillous trophoblasts were isolated from first trimester placental tissue after termination of pregnancy. Biological activities of the cells were studied after treatment with GdA at a physiological dose of 5 μg/mL. GdA was purified from human amniotic fluid by immuno-affinity chromatography.Participants/materials, Setting, Methods: Expression of VEGF, CD9, CD49a, CD151 and CD158a in the cells were determined by flow cytometry. Angiogenic proteins in the spent media of NK cells were determined by cytokine array and ELISA. Blocking antibodies were used to study the functions of the identified angiogenic proteins. Endothelial cell angiogenesis was determined by tube formation and trans-well migration assays. Cell invasion and migration were determined by trans-well invasion/migration assay. Binding of normal and de-sialylated GdA, and expression of L-selectin and siglec-7 on the NK cells were analysed by flow cytometry. The association between GdA and L-selectin on NK cells was confirmed by immunoprecipitation. Extracellular signal-regulated protein kinases (ERK) activation was determined by Western blotting and functional assays.Main Results and the Role Of Chance: GdA treatment enhanced the expression of dNK cell markers CD9 and CD49a and the production of the functional dNK secretory product VEGF in the peripheral blood CD16-CD56bright NK cells. The spent media of GdA-treated CD16-CD56bright NK cells promoted tube formation of human umbilical vein endothelial cells and invasiveness of trophoblasts. These stimulatory effects were mediated by the stimulatory activities of GdA on an ERK-activation dependent production of VEGF and IGFBP-1 by the NK cells. GdA had a stronger binding affinity to the CD16-CD56bright NK cells as compared to the CD16+CD56dim NK cells. This GdA-NK cell interaction was reduced by de-sialylation. GdA interacted with L-selectin, expressed only in the CD16-CD56bright NK cells, but not in the CD16+CD56dim NK cells. Anti-L-selectin functional blocking antibody suppressed the binding and biological activities of GdA on the NK cells.Large Scale Data: N/A.Limitations, Reasons For Caution: Some of the above findings are based on a small sample size of peripheral blood CD16-CD56bright NK cells. These results need to be confirmed with human primary dNK cells.Wider Implications Of the Findings: This is the first study on the biological role of GdA on conversion of CD16-CD56bright NK cells to dNK-like cells. Further investigation on the glycosylation and functions of GdA will enhance our understanding on human placentation and placenta-associated complications with altered NK cell biology.Study Funding/competing Interest(s): This work was supported by the Hong Kong Research Grant Council Grant 17122415, Sanming Project of Medicine in Shenzhen, the Finnish Cancer Foundation, Sigrid Jusélius Foundation and the Finnish Society of Clinical Chemistry. The authors have no competing interests to declare. [ABSTRACT FROM AUTHOR]

[Display omitted] • Glycodelin is a glycoprotein. • Mainly found in amniotic fluid, secretory endometrium, and pregnancy decidua. • Glycodelin is a potential biomarker for various reproductive disorders. • Various traditional methods such as ELISA, SPR, PCR, and western blot etc developed. • However, biosensing technology offers a powerful platform for the rapid, sensitive etc. • Future studies can concentrate on glycodelin immunosensor miniaturization. Glycodelin is a glycoprotein mainly demonstrated in amniotic fluid, secretory endometrium, and pregnancy decidua. Current studies proved that glycodelin is a potential biomarker for various reproductive disorders such as premature ovarian failure, repetitive unprompted abortion, and inexplicable infertility. It has also been reported that glycodelin is demonstrated in various female-specific malignancies, i.e., breast cancer, endometrial cancer, and ovarian cancer, and also expressed in non-gender specific malignancies such as lung and colon cancer. This review article is the first attempt to conglomerate the methods developed for the detection of glycodelin biomarker. To the best of our knowledge, to date, there is no review article published related to biosensing technology developed for the detection of glycodelin. The Glycodelin biosensor showed 1–1000 ng/ml concentration range and 0.43 ng/ml limit of detection. There is a need for the miniaturization of glycodelin biosensing devices to assess the death process, advancement of disorders, and proper therapies. [ABSTRACT FROM AUTHOR]

Purpose: Preeclampsia, in which insufficient trophoblastic invasion is thought to be one of the underlying mechanisms, is a common pregnancy disorder. Glycodelin is a regulator of immunosuppression, fertilization, implantation, and placentation. Because of its inhibitory effects on trophoblastic activity, trophoblast invasion is disturbed when its levels alter. We aimed to analyze serum glycodelin levels in preeclampsia and evaluate whether it correlates with the severity of disease.Methods: This is a prospective case-control study conducted in a research and training hospital between March and September 2016. In this study, a total of 55 preeclamptic and 65 healthy pregnants were included. Preeclamptic patients were divided into two subgroups: 25 severe and 30 mild. Maternal serum glycodelin levels were measured using enzyme-linked immunosorbent assay.Results: Glycodelin levels were higher in preeclamptic group as compared with controls (71.38 ± 22.78 versus 42.32 ± 12.28 ng/ml, p < .001). Also, it was higher in severe preeclampsia than the mild group (84.19 ± 24.58 versus 60.71 ± 14.4 ng/ml, p < .001). Glycodelin was positively correlated with systolic and diastolic blood pressures (r = 0.637 and r = 0.714, respectively, p < .001), aspartate and alanine aminotransferases (r = 0.369, p = .006 and r = 0.377, p = .005) and proteinuria (r = 0.342, p = .011). Moreover, it was correlated with birth weights and gestational age at delivery (r = -0.386, p = .004 and r = -0.394, p = .003, respectively). The role of glycodelin to diagnose preeclampsia was evaluated by receiver operating curve (ROC) curve. Area under the curve for glycodelin is 0.897 with p < .001. The sensitivity of glycodelin was 83.6% and the specificity was 80% at a threshold >53.64 ng/ml. Moreover, area under the curve for glycodelin to diagnose severe preeclampsia is 0.788 with p < .001. The sensitivity of glycodelin was 59% and the specificity was 93.3% at a threshold >83.97 ng/ml.Conclusion: Glycodelin may be a promising marker in predicting the presence and severity of preeclampsia. [ABSTRACT FROM AUTHOR]

Glycodelin (or placental protein 14) is a glycoprotein located in the glandular and thin epithelium of the endometrium. It is considered an important factor in the implantation process, and its traces can be found in elevated concentrations in the uterine flushing obtained at the time of implantation, while in the proliferative phase of the cycle, its levels are low. A certain concentration has been found to inhibit the binding of spermatozoids to the zona pellucida of the oocites therefore, it effects conception. It has a role in angiogenesis and is in high concentrations in the tissues of both benign and malignant gynaecological tumours. The aim of this study is to analyse and display the glycodelin level changes before and after hysteroscopic polypectomy in infertile patients in the uterine flushing fluid and serum. This survey covers 80 infertile patients, who were divided into two groups. The first group, the experimental group, consisted of 50 infertile patients with endometrial polyps, and a control group of 30 infertile patients without endometrial polyps was also included. The results primarily indicate the existence of changes in glycodelin levels preoperatively in the flushing and venous blood in infertile patients with endometrial polyps compared with the levels after surgery. In the control group of patients, no significant change in the glycodelin levels was detected in the flushing and venous blood. When comparing these two groups, statistically significant differences in the glycodelin levels in the flushing and venous blood were noted. We conclude that the presence of endometrial polyps in the cavum uteri affects the increase in the glycodelin concentration in the flushing fluid and in the plasma. Increased glycodelin concentrations complicate fertilization and implantation. [ABSTRACT FROM AUTHOR]

The current study evaluated exosomes isolated from plasma of heifers bred to have high or low fertility through developing extreme diversity in fertility breeding values, however, key animal traits (e.g., body weight, milk production, and percentage of North American genetics) remained similar between the 2 groups. The exosomes were isolated by a combined ultracentrifugation and size exclusion chromatography approach and characterized by their size distribution (nanoparticle tracking analysis), morphology (transmission electron microscopy), and presence of exosomal markers (immunoblotting). In addition, a targeted mass spectrometry approach was used to confirm the presence of 2 exosomal markers, tumor susceptibility gene 101 and flotillin 1. The number of exosomes from plasma of high fertility heifers was greater compared with low fertility heifers. Interestingly, the exosomal proteomic profile, evaluated using mass spectrometry, identified 89 and 116 proteins in the high and low fertility heifers respectively, of which 4 and 31 were unique, respectively. These include proteins associated with specific biological processes and molecular functions of fertility. Most notably, the tetratricopeptide repeat protein 41-related, glycodelin, and kelch-like protein 8 were identified in plasma exosomes unique to the low fertility heifers. These proteins are suggested to play a role in reproduction; however, the role of these proteins in dairy cow reproduction remains to be elucidated. Their identification underscores the potential for proteins within exosomes to provide information on the fertility status and physiological condition of the cow. This may potentially lead to the development of prognostic tools and interventions to improving dairy cow fertility. [ABSTRACT FROM AUTHOR]

A set of poly(lactic-co-glycolic acid) polymers functionalized with different monosaccharides as well as glycodendrimers and surface-decorated nanoparticles (NPs) were synthesized and characterized. The functionalization of the polymer was carried out through amide bond formation with amino-modified sugar monomers and through a biocompatible chemoselective method exploiting the reducing end of a free sugar. The assemblage of the NPs adopting a nanoprecipitation method was straightforward and allowed the preparation of sugars/sugar dendrimer coated NPs. [ABSTRACT FROM AUTHOR]

Summary: Glycodelin is an immunomodulator, indispensable for the maintenance of pregnancy in humans. The glycoprotein induces apoptosis in activated CD4+ T cells, monocytes and natural killer (NK) cells, and suppresses the activity of cytotoxic T cells, macrophages and dendritic cells. This study explores the immunosuppressive property of glycodelin for its possible use in preventing graft rejection. Because glycodelin is found only in certain primates, the hypothesis was investigated in an allograft nude mouse model. It is demonstrated that treatment of alloactivated mononuclear cells with glycodelin thwarts graft rejection. Glycodelin decreases the number of activated CD4+ and CD8+ cells and down‐regulates the expression of key proteins known to be involved in graft demise such as granzyme‐B, eomesodermin (EOMES), interleukin (IL)‐2 and proinflammatory cytokines [tumour necrosis factor (TNF)‐α and IL‐6], resulting in a weakened cell‐mediated immune response. Immunosuppressive drugs for treating allograft rejection are associated with severe side effects. Glycodelin, a natural immunomodulator in humans, would be an ideal alternative candidate. [ABSTRACT FROM AUTHOR]

Glycodelin-A (GdA) has been proposed to represent a potential biomarker of endometrial function, but little is known about its expression during the different phases of the menstrual cycle and under pathological conditions. In the light of its potential importance also in embryo implantation, we aimed to evaluate the expression profile of GdA as well as the presence of different glycosylated glycoforms and the immunolocalization in endometrial tissue from women with endometriosis and in women with proven fertility, at different times during the menstrual cycle. Our results showed that GdA is synthesized by endometrial epithelial and stromal cells, both in healthy endometrium and eutopic endometrium from women with endometriosis, with a profile including several glycosylated glycoforms, differentially expressed in each phase of the menstrual cycle. During the secretory phase, a significant increase in GdA protein expression, with a different glycoforms profile, was observed in endometriotic eutopic endometrium. Protein localization in eutopic endometrial tissue resulted significantly different in comparison with endometrium from women with proven fertility. This study indicate that GdA is a complex glycoprotein including up to 6 different glycoforms specifically expressed during the different phase of the menstrual cycle; in pathologic conditions such as endometriosis, the expression profile is altered possibly related to the impaired endometrial receptivity. [ABSTRACT FROM AUTHOR]

Glycodelin is a kind of glycoprotein expressed in secretory endometrium, pregnancy deciduas, and amniotic fluid originally, which is vital for the maintenance of normal human reproductive activities. Recent researches have reported that glycodelin is specifically expressed in various malignancies, including female-specific cancers such as endometrial cancer, ovarian cancer and breast cancer, and non-gender specific cancers including lung cancer, and colon cancer, and glycodelin expression correlates with the diagnosis and prognosis of cancer patients. This review focuses on the expression of glycodelin in different cancers and its role in cancer development and progression. Glycodelin possesses the abilities to regulate cancer cell proliferation, differentiation, and invasion, promote cancer angiogenesis, and modulate the differentiation and function of immune cells including T cells, dendritic cells, monocyte-macrophages, natural killer cells and B cells participating in cancer development. The expression of glycodelin can be regulated by stromal cells, lysophosphatidic acid, histone deacetylase inhibitors, and relaxin. In summary, glycodelin is a promising biomarker for the diagnosis and prognosis of cancer patients, and depending on its distinct immunoregulatory effects, glycodelin can be a prospective target for cancer immunotherapy.

Background and Objective: Glycodelin expression in normal and cancerous human breast tissue and its relation with age, tumor type, microscopic grade and metastasis to axillary lymph nodes recently were noticed. This study was done to evaluate the glycodelin expression in breast cancer. Methods: In this descriptive study, 96 Paraffin-embedded blocks of malignant breast cancer by immunohistochemistry method were considered to evaluate the expression of glycodelin. Patients age,tumor size, tumor type, microscopic grade and metastasis to axillary lymph nodes were recorded for each subject. Results: Glycodelin was found in 30.45% of invasive carcinoma of the breast with axillary lymph node metastasis. Glycodelin was expressed in 72.7% of carcinoma of the breast without lymph nodes metastasis (P

Background: Endometriosis is a benign chronic disease, characterized by the presence and proliferation of functional endometrial gland and stroma outside the uterine cavity. Objective: To evaluate the usefulness of intracellular adhesion molecule-1 (ICAM-1) and Glycodelin (Gd) as a biomarker for the diagnosis of endometriosis and to help in detection of various stages of endometriosis. Methods: Forty-four patients with endometriosis and 35 apparently healthy women as control were enrolled in this study from November 2015 to April 2016. All individuals were subjected to blood sampling for measuring their serum ICAM-1 and Gd A level by using enzyme linked immune sorbent assay technique. Results: The current study revealed significantly higher serum levels of ICAM-1 and Gd in patients group in comparison with healthy control. In addition, the sensitivity and specificity for ICAM-1 and Gd A in serum were 61%/66%, 76%/85% respectively. Conclusion: The ICAM-1 and Gd A level in serum may be useful as noninvasive test for diagnosis of endometriosis in all stages. [ABSTRACT FROM AUTHOR]

The aim of this cross-sectional study is to compare endometrial flushing fluid levels of αVβ3integrin, glycodelin and PGF2α during the midluteal phase of the menstrual cycle of women with polycystic ovary syndrome (PCOS,n = 20), myoma uteri (n = 20) and endometrioma (n = 19) with the healthy controls (n = 20). After collecting samples at the midluteal phase of ovulatory volunteers and storing them at −80 °C, αVβ3integrin, glycodelin and PGF2α levels were analyzed using ELISA. The mean ages of the groups were 28.90 ± 5.45, 37.25 ± 2.73, 32.84 ± 6.62 and 32.15 ± 5.18 in PCOS, myoma uteri, endometrioma and control groups, respectively. The αVβ3integrin level (ng/ml) was statistically significantly higher in endometrioma group (9.70 ± 1.72,p < 0.05) as compared to myoma uteri and control groups. Similarly, glycodelin level (ng/ml) was significantly higher in endometrioma group (341.04 ± 93.32) than PCOS (p < 0.01), myoma uteri (p < 0.001) and healthy subjects (p < 0.001). Moreover, PGF2α level (350.04 ± 464.50 ng/ml) was significantly higher in PCOS group relative to myoma uteri (p < 0.001), endometrioma (p < 0.05) and control (p < 0.05) groups. In conclusion, αVβ3integrin level was significantly higher in endometrioma subjects than those with myoma uteri and control groups; glycodelin level was significantly higher in endometrioma group than other three groups, and lastly, PCOS patients had significantly higher PGF2α levels than those patients with myoma uteri, endometrioma and controls. [ABSTRACT FROM PUBLISHER]

The present study aimed to identify differences in protein expression in cases of endometrioid endometrial cancer (EEC) with and without coexisting adenomyosis uteri (AM), and to evaluate the histopathological and prognostic distinctions. The total cohort included 22 patients in Group A (patients with concomitant AM and EEC) and 35 patients in Group B (patients affected only by EEC). Evaluation of the following factors was performed: Tumour grade, International Federation of Gynaecology and Obstetrics (FIGO) stage, survival, and expression of estrogen receptor β (ERβ), glycodelin and inhibin βB. Group A (AM and EEC) was associated with a lower tumour grade (G1, 90.9 vs. 45.7%; P=0.001) and a lower FIGO stage (FIGO stage I, 100 vs. 80%; P=0.002) compared with Group B (EEC only). In the survival analysis, Group A was associated with a significantly higher 5-year survival rate (95 vs. 82%; P=0.024) than Group B. In addition, the expression of ERβ in Group A was significantly higher (P<0.001), whereas the expression of glycodelin is significantly lower (P=0.028), compared with Group B. The results of the present study indicate that the presence of AM in cases of EEC may be a positive prognostic factor. [ABSTRACT FROM AUTHOR]

Introduction Glycodelin is a glycoprotein with different oligosaccharides that are responsible for its diverse biological functions in contraception and immunosuppression. Therefore, it is necessary to have access to adequate amounts of glycodelin with retained carbohydrate structure for functional studies because the carbohydrate part can be lacking or be insufficient in recombinant glycodelin from prokaryotic and eukaryotic cell systems. Methods and results Native glycodelin was purified from amniotic fluid by a series of affinity chromatography steps and had many glycosylated forms verified by mass spectrometry. About 7.5 mg glycodelin was obtained from 1.5 L amniotic fluid. No high molecular mass forms of glycodelin were found in amniotic fluid. Aliquots of the purified glycodelin were used as an immunogen in rabbits for antibody production against glycodelin and a calibrator in a highly sensitive glycodelin enzyme-linked immunosorbent assay (ELISA) with a detection limit of about 1 μg/L. Conclusions Native glycodelin was purified from amniotic fluid and used as an immunogen for raising a rabbit antibody against glycodelin and a calibrator in a highly sensitive glycodelin ELISA. We found no high molecular mass forms of glycodelin in amniotic fluid. Aliquots of the purified glycodelin were set aside for functional studies which are in progress. [ABSTRACT FROM AUTHOR]

Introduction: Miscarriage is a major concern in early pregnancy among women having conceived with assisted reproductive treatments. This study aimed to examine potential miscarriage-related biophysical and biochemical markers at 6 weeks' gestation among women with confirmed clinical pregnancy following in vitro fertilization (IVF)/embryo transfer (ET) and evaluate the performance of a model combining maternal factors, biophysical and biochemical markers at 6 weeks' gestation in the prediction of first trimester miscarriage among singleton pregnancies following IVF/ET., Material and Methods: A prospective cohort study was conducted in a teaching hospital between December 2017 and January 2020 including women who conceived through IVF/ET. Maternal mean arterial pressure, ultrasound markers including mean gestational sac diameter, fetal heart activity, crown rump length and mean uterine artery pulsatility index (mUTPI) and biochemical biomarkers including maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), kisspeptin and glycodelin-A were measured at 6 weeks' gestation. Logistic regression analysis was carried out to determine significant predictors of miscarriage prior to 13 weeks' gestation and performance of screening was estimated by receiver-operating characteristics curve analysis., Results: Among 169 included pregnancies, 145 (85.8%) pregnancies progressed to beyond 13 weeks' gestation and had live births whereas 24 (14.2%) pregnancies resulted in a miscarriage during the first trimester. In the miscarriage group, compared to the live birth group, maternal age, body mass index, and mean arterial pressure were significantly increased; mean gestational sac diameter, crown rump length, mUTPI, serum sFlt-1, glycodelin-A, and the rate of positive fetal heart activity were significantly decreased, while no significant differences were detected in PlGF and kisspeptin. Significant prediction for miscarriage before 13 weeks' gestation was provided by maternal age, fetal heart activity, mUTPI, and serum glycodelin-A. The combination of maternal age, ultrasound (fetal heart activity and mUTPI), and biochemical (glycodelin-A) markers achieved the highest area under the curve (AUC: 0.918, 95% CI 0.866-0.955), with estimated detection rates of 54.2% and 70.8% for miscarriage before 13 weeks' gestation, at fixed false positive rates of 5% and 10%, respectively., Conclusions: A combination of maternal age, fetal heart activity, mUTPI, and serum glycodelin-A at 6 weeks' gestation could effectively identify IVF/ET pregnancies at risk of first trimester miscarriage., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)