Journal of Reproductive Immunology (J REPROD IMMUNOL)

Publications in this journal

• Article: Prior reproductive experience alters prolactin-induced macrophage responses in pregnant rats

  Maria Isabel R Carvalho-Freitas, Janete A Anselmo-Franci, Joao Palermo-Neto, Luciano F Felicio
  Journal of Reproductive Immunology 01/2013;
• Article: Extra-villous trophoblast cytoskeleton deformation under co-infection with viral and bacterial agents.

  Jabeen, Alkhatib, Hicks, C.E, Uddin, Hakam, S.M, Jain, Fernández
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  ABSTRACT: Extra-villous trophoblast cytoskeleton deformation under co-infection with viral and bacterial agents. Jabeen, A.; Hicks, C.; Uddin, T.; Hakam, S. M.; Jain. P; Laissue, P. and Fernández, N. School of Biological Sciences, University of Essex, Colchester, United Kingdom E-mail: ajabee@essex.ac.uk Problem: Cytoskeleton integrity is linked with cell viability, gene expression and normal cell physiology. In implantation, the extra-villous trophoblast (EVT) cytoskeleton integrity is crucial for successful maternal endometrium invasion and cell adhesion. Here we investigate the physical deformation of trophoblast cytoskeleton in response to infections with either lipopolysaccharide (LPS) or Polyinosinic: polycytidylic acid (poly: IC) alone and co-infection, where EVT cell model JEG-3 pre-treated with poly:IC and then with LPS. Methods:JEG-3 cells monolayer cultured chamber slide and either untreated or treated for 24h. Cells were fixed, permeabilized and stained with beta-tubulin-Alexa 488 antibody for microtubules. Rhodamine Phalloidin was used for microfilament staining. Three dimensional (3D) stack images were acquired with Nikon A1R confocal microscope using a 1.4 N.A. 60x magnifying oil-immersion objective and 29.38µm pinhole. Composite projections of 3D stacks were imported to Image J to calculate corrected total cell fluorescence (CTCF) for tubulin and F-actin. Results: CTCF for F-actin is markedly decreased in cells pre-treated with poly:IC and then with LPS as compared to untreated and samples treated with LPS or poly:IC alone. Whereas, CTCF for tubulin was increased in LPS only and co-infection samples while decreased in poly: IC only treated samples as compared to control group. Tubulin depolymerization was observed with 55kDa and 25kDa bands in co-infection and LPS only samples. Only 55kDa tubulin was seen in untreated and poly:IC alone samples. These results indicate that LPS only and co-infection causes tubulin depolymerisation in 24 hours. JEG-3 cells with co-infection showed significantly lower cell growth. Conclusion:EVT cytoskeleton deformation might be used as an early diagnosis for cell apoptosis. The trophoblast cell model JEG-3 respond to LPS more strongly when pre-treated with poly:IC, suggesting that poly:IC sensitizes the trophoblast making it susceptible to bacterial infection.
  Journal of Reproductive Immunology 05/2012; 94(1):69.
• Article: Stage-related changes of peritoneal soluble TNFα and TNFR1 and TNFR2 in cells recovered from peritoneal fluid of women with endometriosis.

  Antonio Simone Laganà, Francesca Maria Salmeri, Giovanni Retto, Emanuele Sturlese, Alfonsa Pizzo, Rosanna De Dominici, Vincenza Sofo
  Journal of Reproductive Immunology 05/2012; 94(1):94-95.
• Article: The role of the cytoskeleton in foeto-maternal immunotolerance.

  A. Blanch, P. Jain, A. Jabeen, N. Fernandez
  Journal of Reproductive Immunology 01/2012; 94(1):106.
• Article: Study of MHC class I molecules associations: Is receptor interaction at the cell-surface important at the feto-maternal interface?

  Jabeen, Asma, Laissue, Philippe P, Jain, Shakhawat, Shaikly, Fernández, Nelson
  Journal of Reproductive Immunology 01/2011; 90(2):144-145.
• Article: Physical interactions of HLA-G with MHC class I partner molecules on the surface of two trophoblast cell lines, JEG-3 and ACH-3P, by Forster resonance energy transfer based on fluorescence lifetime measurements.

  Jabeen, Asma, Jain, Laissue, Philippe P, Suhling, Levitt, J A, Shaikly, Shakhawat, Fernández, Nelson
  Journal of Reproductive Immunology 01/2010; 86(2):20.
• Article: WITHDRAWN: Effects of implantation and early pregnancy on the expression of cytokines and vascular surface molecules in the sheep endometrium.

  Abu Nasar Md, Aminoor Rahman, Kenneth J Snibson, Chee Seong Lee, Els N T Meeusen
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  ABSTRACT: This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
  Journal of Reproductive Immunology 04/2009;
• Article: Nerve fibers in uterosacral ligaments of women with deep infiltrating endometriosis.

  Adolpho Roberto Kelm Junior, Carmen Lucia P Lancellotti, Nilson Donadio, Antonio Pedro F Auge, Sonia Maria Rolim R Lima, Tsutomu Aoki, Paulo Ayroza Ribeiro
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  ABSTRACT: Endometriosis is a disease of high prevalence and enigmatic origin. One aspect not yet clarified is the relationship between endometriosis and nerve tissue. To evaluate, by immunohistochemistry, the presence of sympathetic and parasympathetic nerve fibers in the uterosacral ligament and adjacent connective tissue in women with deep pelvic endometriosis and women without endometriosis. Cross-sectional study (Canadian Task Force II). University Hospital. Obstetrics and Gynecology Department, Santa Casa Medical School, São Paulo, Brazil. We selected 49 patients, 20 of them with deep endometriosis in the uterosacral ligament and 29 patients without endometriosis. Secondary antibodies to NSE (pan-neuronal marker), NPY (that identifies sympathetic nerve fibers), and VIP (that identifies parasympathetic nerve fibers) were used for the immunohistochemistry analyses. The immunohistochemical staining by the NSE antibody was positive in 40% of cases of women with endometriosis and in 20.7% of patients without endometriosis (non-significant). The immunohistochemical staining by the NPY antibody was positive in 60% of patients with endometriosis and in 20.7% of the control group (p=0.005), while staining by the VIP antibody was 60% in patients with endometriosis and 13.8% in patients without endometriosis (p=0.001). Immunoexpression of NPY (sympathetic fibers) and VIP (parasympathetic fibers) is higher in women with deep pelvic endometriosis than in women without endometriosis.
  Journal of Reproductive Immunology 11/2008; 79(1):93-9.
• Article: Maternal and fetal C-reactive protein genotype and first trimester CRP concentrations in maternal plasma.

  David N Hackney, James T Dunigan, Hyagriv N Simhan
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  ABSTRACT: Maternal plasma CRP concentrations in pregnancy are increased over pre-pregnancy values and high concentrations have been associated with adverse obstetrical outcomes. The objective of this study was to explore the relationship between maternal and fetal variation in C-reactive protein (CRP) genotype and maternal plasma CRP concentrations in the first trimester in low risk patients. DNA was extracted from maternal and cord blood of subjects in a prospective observational cohort. Single-nucleotide polymorphism (SNP) selection was made using a linkage disequilibrium bin approach. CRP concentrations were measured in first trimester maternal plasma using an enzyme-linked immunosorbent assay (ELISA) kit. Kruskal-Wallis rank testing was used to analyze genetic and clinical determinants of CRP concentrations. Genotype results were available in 190 mother-baby pairs. There was no significant difference in CRP concentration among maternal or fetal CRP genotypes. Thus, first trimester concentrations of maternal plasma CRP in low risk subjects do not appear to be significantly associated with CRP genotype. Instead, differences in clinical factors probably have more influence on baseline maternal CRP concentrations.
  Journal of Reproductive Immunology 10/2008; 79(1):44-9.
• Article: Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia.

  Maria Terezinha Serrão Peraçoli, Fernanda Tereza Ferreira Menegon, Vera Therezinha Medeiros Borges, Roberto Antonio de Araújo Costa, Izolete Aparecida Thomazini-Santos, José Carlos Peraçoli
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  ABSTRACT: Platelets and transforming growth factor-beta(1) (TGF-beta(1)) are thought to be involved in the pathogenesis of preeclampsia. Our objectives were to determine plasma concentration of TGF-beta(1) in normotensive and preeclamptic women in the third trimester of pregnancy and to evaluate the correlation of TGF-beta(1) plasma levels with platelet count and agonist-induced aggregation capacity. Thirty-three women with preeclampsia were compared with 36 healthy women with uncomplicated pregnancies. Peripheral venous blood samples were obtained, and TGF-beta(1) plasma levels measured by an enzyme-linked immunoassay. Platelet aggregation was induced by the agonist agents adenosine diphosphate (ADP), collagen and epinephrine, and was determined in platelet-rich plasma by aggregometry. Plasma concentrations of active TGF-beta(1) were significantly higher in preeclamptic women (10.41+/-2.07ng/mL) compared with normotensive pregnant women (7.01+/-3.29ng/mL). Platelet number and platelet agonist-induced aggregation percent were significantly lower in patients with preeclampsia than in healthy pregnant women. A significant correlation was observed between TGF-beta(1) plasma levels and platelet agonist-induced aggregation percent as between plasma levels of TGF-beta(1) and platelet number in preeclamptic patients. The association between impairment in platelet responsiveness and higher levels of TGF-beta(1) in the plasma of patients with preeclampsia suggests that this cytokine may play a role in the pathophysiological events of preeclampsia that are dependent on platelet activation.
  Journal of Reproductive Immunology 10/2008; 79(1):79-84.
• Article: Association of leptin with inflammatory cytokines and lymphocyte subpopulations in peritoneal fluid of patients with endometriosis.

  Łukasz Milewski, Ewa Barcz, Piotr Dziunycz, Dariusz Radomski, Paweł Kamiński, Piotr I Roszkowski, Grazyna Korczak-Kowalska, Jacek Malejczyk
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  ABSTRACT: Endometriosis is a common, complex and chronic disease related to ectopic implantation and growth of endometrial tissue that may manifest by pelvic inflammatory reactions, chronic pelvic pain and subfertility. Endometriosis may be associated with increased peritoneal fluid leptin levels. Leptin is known to exert immunomodulatory effects; however, an association between leptin and inflammatory reactions in endometriosis has not been documented. Therefore, the aim of this study was to investigate a relationship between leptin concentrations in peritoneal fluid and the levels of peritoneal fluid inflammatory cytokines and mononuclear leukocyte subpopulations. Peritoneal fluid was aspirated by laparoscopy from 46 women in whom endometriosis had been confirmed by clinical and histopathological examinations and from 10 control women qualified for ART in whom pelvic pathology has been excluded. Concentrations of leptin and inflammatory cytokines (IL-1beta, IL-6, IFN-gamma and TNF) in peritoneal fluid were evaluated by specific ELISAs. Percentage of peritoneal leukocyte subpopulations (CD3+, CD4+, CD8+ and CD14+) was analyzed by FACS using specific monoclonal antibodies. Leptin concentrations in peritoneal fluid correlated negatively with concentrations of IL-1beta and IFN-gamma (r(s)=-0.38, p=0.01 and r(s)=-0.31, p=0.03, respectively) and correlated positively with the percentage of CD3+ pan-T cells (r(s)=0.69, p=0.009) and CD4+ T helper cells (r(s)=0.74, p=0.036). Increased leptin levels in peritoneal fluid from endometriosis patients may affect local inflammatory/immune reactions, especially infiltration of CD4+ T helper cells. Thus, leptin may play an important role in the immunopathogenesis of endometriosis.
  Journal of Reproductive Immunology 10/2008; 79(1):111-7.
• Article: Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by epithelial cells of the male reproductive tract.

  Mattias Collin, Helena M Linge, Anders Bjartell, Aleksander Giwercman, Johan Malm, Arne Egesten
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  ABSTRACT: The reproductive tract is continuously challenged by potential pathogens present in the environment. Therefore, robust host defense mechanisms are essential both for the health of the individual and for fertilization. Antibiotic innate immunity peptides possess broad antimicrobial activity. Recently, we found that the CXC chemokine, granulocyte chemotactic protein (GCP)-2/CXCL6, possesses antibacterial activity. In the present study, we investigated, therefore, the presence of GCP-2/CXCL6 in the human male reproductive system. GCP-2/CXCL6 was detected at 19nM (mean; range: 5-47nM; n=14) in seminal plasma of fertile donors, i.e. at levels more than 100 times higher than those previously reported for the related chemokine IL-8/CXCL8. No GCP-2/CXCL6 could be detected in blood plasma of healthy donors, indicating local production in the male reproductive tract. In vasectomized donors, significantly lower levels of GCP-2/CXCL6 were found (mean: 3nM; range 2-7nM; n=7), demonstrating that the testis and epididymis contribute significantly to the GCP-2/CXCL6 content of seminal plasma. Strong expression of GCP-2/CXCL6 was found in the epithelium of the testis, epididymis and seminal vesicles, while the prostate epithelium showed weak expression, as determined by immunohistochemistry. A biological function is suggested, viz. at concentrations of the order of those found in seminal plasma, GCP-2/CXCL6 has antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. GCP-2/CXCL6 in seminal plasma may play roles in both host defense of the male urogenital tract and during fertilization.
  Journal of Reproductive Immunology 10/2008; 79(1):37-43.
• Article: Uterine natural killer cells are immunogenic in syngeneic male mice.

  Marcia C Bizinotto, Wirla M S C Tamashiro, Dirce L Gabriel, Aureo T Yamada
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  ABSTRACT: Uterine natural killer (uNK) cells expand rapidly during endometrial decidualization and account for 70% of leukocytes in early gestational uteri of humans and rodents. These cells make unique contributions to pregnancy, contributing to the success of embryo implantation and maintenance of decidual tissue that supports placental and fetal development. We postulated that uNK cells express molecules that are not shared by circulating NK (cNK) cells or other leukocytes and, therefore, would be immunogenic for male mice. We isolated viable uNK cells from gestation day 9 pregnant mice and inoculated them into syngeneic males. This induced antibodies reactive with mouse uNK cells but not with cNK cells or other lymphocytes. The antibodies reacted identically with uNK cells in tissue sections from five different mice strains from gestational day 7-12 and in pregnant rat uterus, suggesting that the recognized antigen should be a specific marker of uNK cell. Spleen cells from inoculated males were used subsequently to produce a monoclonal antibody reactive to a uNK cell surface antigen. These experiments confirm that uNK cells are a pregnancy-specific subset of NK cells expressing distinct surface antigen from those found in other tissues.
  Journal of Reproductive Immunology 10/2008; 79(1):18-25.
• Article: Human trophoblast cells express the immunomodulator progesterone-induced blocking factor.

  C Anderle, A Hammer, B Polgár, M Hartmann, R Wintersteiger, A Blaschitz, G Dohr, G Desoye, J Szekeres-Barthó, P Sedlmayr
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  ABSTRACT: Progesterone-induced blocking factor (PIBF) is an immunomoduatory factor with anti-abortive properties. In this study, we present evidence that PIBF is synthesized in the human placenta and determine its cellular source. Expression of PIBF was analysed with polyclonal rabbit anti-human PIBF antibodies against recombinant N-terminal 48kDa PIBF in first trimester and term placental tissues and in the choriocarcinoma cell line JAR by means of immunohistochemistry, confocal laser scanning microscopy of double immunofluorescence labelling, and Western blotting; RT-PCR was performed for analysis of PIBF mRNA in isolated trophoblast cells. PIBF protein is present in human first trimester and term placenta. Double immunofluorescence labelling localised PIBF to the extravillous cytotrophoblast. PIBF is also expressed heterogeneously by syncytiotrophoblast and part of the villous cytotrophoblast. Full-length PIBF mRNA encoded by exons 1-18 is present in isolated first trimester and term villous trophoblast and in the choriocarcinoma cell line JAR. The corresponding 90kDa protein is expressed by JAR cells, first trimester and term villous trophoblast cells. In addition, these cells express PIBF proteins of 50 and 34kDa. Trophoblast is a source of PIBF; its tissue distribution suggests a role both in systemic and local (decidual) immunoregulation.
  Journal of Reproductive Immunology 10/2008; 79(1):26-36.
• Article: Autoantibodies to folate receptor during pregnancy and neural tube defect risk.

  Robert M Cabrera, Gary M Shaw, Johnathan L Ballard, Suzan L Carmichael, Wei Yang, Edward J Lammer, Richard H Finnell
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  ABSTRACT: Periconceptional folic acid can reduce the occurrence of neural tube defects (NTDs) by up to 70%, and autoantibodies for folate receptors (FRs) have been observed in serum from women with a pregnancy complicated by an NTD. This population-based cohort study has examined serum from pregnant mothers for autoantibodies to FRs, antibodies to bovine folate binding protein (FBP), and inhibition of folic acid binding to FR and FBP in association with NTD risk. The mid-gestational maternal serum specimens used for this study were collected during the 15-18th week of pregnancy. Samples were obtained from the California Birth Defects Monitoring Program; 29 mothers had a pregnancy complicated by spina bifida and 76 mothers had unaffected children. The presence of IgG and IgM antibodies to human FR, bovine FBP, and inhibition of folic acid binding to FR and FBP was determined. Higher activity of IgM to FBP in cases verses controls was observed (P=0.04). Higher activity of IgM and IgG autoantibodies to FR was observed (P<0.001 and P=0.04, respectively). Risk estimates at two standard deviations above average control antibody concentrations were OR=2.07 (CI=1.02, 4.06) for anti-FBP IgM, OR=2.15 (CI=1.02, 4.69) for anti-FR IgG and OR=3.19 (CI=1.47, 6.92) for anti-FR IgM. These data support the hypothesis that high titers of antibodies and blocking of folic acid binding to FRs by maternal serum should be regarded as risk factors for NTDs.
  Journal of Reproductive Immunology 10/2008; 79(1):85-92.
• Article: Mid-pregnancy circulating cytokine levels, histologic chorioamnionitis and spontaneous preterm birth.

  Julia Warner Gargano, Claudia Holzman, Patricia Senagore, Poul Thorsen, Kristin Skogstrand, David M Hougaard, Mohammad H Rahbar, Hwan Chung
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  ABSTRACT: Some spontaneous preterm deliveries (PTD) are caused by occult infections of the fetal membranes (histologic chorioamnionitis [HCA]). High levels of infection-related markers, including some cytokines, sampled from maternal circulation in mid-pregnancy have been linked to PTD, but whether these specifically identify HCA has not been established. We have tested associations between 13 Th1, Th2 and Th17 cytokines and PTD with and without HCA in a prospective cohort study. The study sample included 926 Pregnancy Outcomes and Community Health Study subcohort women; women with medically indicated PTD or incomplete data excluded. A panel of cytokines was assessed using a multiplex assay in maternal plasma collected at 15-27 weeks of gestation. Severe HCA was scored by a placental pathologist blinded to clinical variables. Multivariable polytomous logistic regression was used to estimate adjusted odds ratios (OR) per 1 standard deviation (S.D.) increase in cytokine levels using a 5 level outcome variable: PTD <35 weeks with HCA, PTD <35 weeks without HCA, PTD 35-36 weeks with HCA, PTD 35-36 weeks without HCA, and term (referent). Interleukin (IL)-1beta, IL-2, IL-12, interferon-gamma, IL-4, IL-6 and transforming growth factor-beta were all significantly associated with PTD <35 weeks with HCA, with ORs of 1.6-2.3 per S.D. increase. None of these were associated with PTD <35 weeks without HCA or PTD 35-36 weeks with HCA. Although the tissues of origin of circulating cytokines are unclear, the observed elevations across many cytokines among women who later delivered <35 weeks with HCA may represent a robust immune response to infection within gestational tissues. These results suggest that women with HCA could be identified using relatively non-invasive means.
  Journal of Reproductive Immunology 09/2008; 79(1):100-10.
• Article: Heat shock protein-containing exosomes in mid-trimester amniotic fluids.

  Alexzander Asea, Claudel Jean-Pierre, Punit Kaur, Preethi Rao, Iara M Linhares, Daniel Skupski, Steven S Witkin
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  ABSTRACT: Exosomes are multivesicular bodies formed by inverse membrane budding into the lumen of an endocytic compartment. Fusion with the plasma membrane leads to their release into the external milieu. The incorporation of heat shock proteins into exosomes has been associated with immune regulatory activity. We have examined whether heat shock protein-containing exosomes are present in mid-trimester amniotic fluid. Exosomes were isolated from mid-trimester amniotic fluids by sequential low-speed and high-speed centrifugation followed by sucrose density gradient centrifugation. Biochemical characterization included floatation pattern in sucrose gradients, acetylcholinesterase (AChE) activity and Western blot analysis for exosome-containing proteins. Exosomes were present in each of 23 amniotic fluids tested. They banded at a density of 1.17g/ml in sucrose gradients, were positive for AChE activity and contained tubulin, the inducible 72kDa heat shock protein, Hsp72 and the constitutively expressed heat shock protein, Hsc73; they were negative for calnexin. Exosome concentrations correlated positively with the number of pregnancies. Heat shock protein-containing exosomes are constituents of mid-trimester amniotic fluids and may contribute to immune regulation within the amniotic cavity.
  Journal of Reproductive Immunology 09/2008; 79(1):12-7.
• Article: Increased circulating paternal antigen-specific IFN-gamma- and IL-4-secreting cells during pregnancy in allergic and non-allergic women.

  Marie Persson, Christina Ekerfelt, Jan Ernerudh, Leif Matthiesen, Maria Jenmalm, Yvonne Jonsson, Martina Sandberg, Göran Berg
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  ABSTRACT: Allergic women have been reported to give birth to more children than non-allergic women, speculatively explained by the former's predisposition for Th2 polarization, possibly favoring pregnancy. The aim of this study was to test the hypothesis that allergy is associated with more Th2-deviated responses to paternal antigens throughout pregnancy. Blood samples were collected on six occasions during pregnancy and two occasions postpartum (pp). Of the 86 women initially included, 54 women had a normal pregnancy and completed the sampling procedures. Eleven women fulfilled the strict criteria for allergy (allergic symptoms and circulating IgE antibodies to inhalant allergens) and 23 were strictly non-allergic (non-sensitized without symptoms). The numbers of blood mononuclear cells secreting IFN-gamma and IL-4, spontaneously and in response to paternal alloantigens, were compared between the groups. The numbers of spontaneously as well as paternal antigen-induced IFN-gamma- and IL-4-secreting cells were similar in allergic and non-allergic pregnant women on all occasions. A similar increase in the numbers of both IFN-gamma- and IL-4-secreting cells were found in allergic and non-allergic women during pregnancy, both regarding spontaneous and paternal antigen-induced secretion. This study does not support the hypothesis of a more pronounced Th2-deviation to paternal antigens in allergic pregnant women compared with non-allergic pregnant women, as measured by number of cytokine-secreting cells. The observed increase of both IFN-gamma- and IL-4-secreting cells during normal pregnancy may be interpreted as a Th2-situation, since the effects of IL-4 predominate over the effects of IFN-gamma.
  Journal of Reproductive Immunology 09/2008; 79(1):70-8.