Journal of Reproductive Immunology RSS feed: Articles in Press. The aim of the Journal of Reproductive Immunology is to provide the critical forum for the dissemination of results from high quality research in all aspects of experimental, animal and clinical reproductive immunobiology. This encompasses normal and pathological processes of: * Male and Female Reproductive Tracts * Gametogenesis and Embryogenesis * Implantation and Placental Development * Gestation and Parturition * Mammary Gland and Lactation INCLUDING: * Infectious disease, including STDs * Inflammation * Autoimmunity * Mucosal Immunology * Cytokines and Other Immune Mediators * Immunoendocrinology * Reproductive Immunotherapies * Immunogenetics * Developmental Immunology * Immunology of Reproductive Cancers * Application of Immunological Techniques in Eluciation of Reproductive Processes or Dysfunction The international character of the Journal is reflected in the breadth of its Editorial Board and commitment to publish new and outstanding studies in different aspects of reproductive immunobiology from all five continents. Within the Journal, the Editors wish to bridge the gap between basic and clinical studies in all subareas of research relevant to reproductive immunobiology.http://www.jrijournal.org//inpress?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. Journal of Reproductive Immunology0165-03782010-07-26 © 2010 Published by Elsevier Inc. healthpermissions@elsevier.comhttp://www.jrijournal.org/article/PIIS0165037810002743/abstract?rss=yesAbstract: Although the female genital tract is the main portal of entry for sexually transmitted infections in women, we still have limited understanding of the generation, maintenance and characteristics of memory T cells in the local tissue. Here, we utilized a mouse model of intravaginal HSV-2 infection and tetramers against the immunodominant HSV glycoprotein B epitope recognized by CD8+ T cells to examine the generation, maintenance and characteristics of anti-HSV memory T cells in the genital tract following acute infection. Our results show that the highest percentage of gB-specific CD8+ T cells was found in the genital tract compared to the spleen or iliac lymphnode. Indeed, although the actual number of CD8+ T cells contracted following viral clearance, approximately one quarter of the CD8+ population that remained in the genital tissue was HSVgB-specific. Memory gB-tetramer+CD8 T cells in the genital tract were positive for CD127 and KLRG1 and negative for CD62L and CCR7, thus confirming that HSV-specific CD8 cells were effector memory T cells that lack the capacity for homing to lymphoid tissues. Functionally, both memory CD8+ and CD4+ HSV-specific populations in the genital tract produced IFNγ when stimulated in vitro and CD4+ cells also produced TNFα. Genital HSVgB-specific memory T cells expressed tissue-homing integrins CD103 (αE integrin) and CD49a (VLA-1 or α1 integrin). Our findings suggest that HSV-specific memory T cells are retained in the genital tract, poised to act as an early line of defense against future virus encounter.Intravaginal infection with herpes simplex virus type-2 (HSV-2) generates a functional effector memory T cell population that persists in the murine genital tract - Uncorrected ProofVera A. Tang, Kenneth L. Rosenthal10.1016/j.jri.2010.06.155Journal of Reproductive Immunology (2010)2010-07-26Journal of Reproductive Immunology2010-07-26http://www.jrijournal.org/article/PIIS0165037810002731/abstract?rss=yesAbstract: Interleukin-23 (IL-23) is a novel cytokine involved in the regulation of organ-specific immune responses. We hypothesized that expression of IL-23 in the human endometrium is menstrual cycle and pregnancy dependent, and is involved in endometrial immune regulation. IL-23 expression and regulation was investigated in the human endometrium and placenta in vivo using immunohistochemistry and in vitro using Western blot and cell viability analyses. IL-23 immunoreactivity in endometrial glandular cells was highest in the late proliferative and early secretory phases, as compared to other cycle phases and first trimester tissues. Endometrial stromal cells (ESC) showed weak IL-23 immunoreactivity without significant changes in intensity and distribution throughout the menstrual cycle. First trimester decidual cells revealed significantly stronger IL-23 staining compared to ESC from non-pregnant endometrium. Both villous cytotrophoblasts and syncytiotrophoblasts also showed positive IL-23 immunoreactivity, with a higher staining in syncytiotrophoblasts. In the trophoblastic cell line HRT8, IL-23 expression increased in a time-dependent manner, but was undetectable in stromal cells under all treatment conditions. ESC treated with recombinant IL-23 showed significantly decreased IL-8 secretion and cell viability. These results suggest a possible regulatory role for IL-23 in the menstrual cycle and in early pregnancy, although the extent and function of this role are yet to be determined.Expression and role of interleukin-23 in human endometrium throughout the menstrual cycle and early pregnancy - Uncorrected ProofYesim H. Uz, William Murk, Celal Emre Yetkin, Umit A. Kayisli, A. Arici10.1016/j.jri.2010.06.154Journal of Reproductive Immunology (2010)2010-07-23Journal of Reproductive Immunology2010-07-23http://www.jrijournal.org/article/PIIS0165037810001026/abstract?rss=yesAbstract: Upper genital tract infections can inflict inadequate immune response and cause Fallopian tube damage and concomitant female infertility. However, the exact role of host genetic variation in the development of tubal factor infertility remains unclear. We selected nine genetic variations in four genes involved in immune response modulation (CCR5, TLR2, TLR4 and MBL2) and assessed their association with tubal factor infertility by comparing genotype frequencies among 163 women with tubal factor infertility and 400 control individuals. The CCR5, TLR2 and TLR4 genotypes were not associated with tubal factor infertility, although the TLR4 Asp299Gly and Thr399Ile heterozygosity was associated with a decreased incidence of pathogens associated with genital tract infections in tubal factor infertility patients. In contrast, MBL2 low-producing genotypes were associated with an increased incidence of such pathogens. In addition, hyper-producing MBL2 genotype HYA/HYA and low-producing MBL2 genotypes were associated with susceptibility to tubal factor infertility, while a protective effect was associated with the high-producing MBL2 genotype HYA/LYA. Overall, these data suggest that polymorphisms in TLR4 and MBL2 play a role in receptiveness to pathogens causing genital tract infections, while MBL2 genotypes contribute to susceptibility to tubal factor infertility.Association of CCR5, TLR2, TLR4 and MBL genetic variations with genital tract infections and tubal factor infertility - Corrected ProofTriin Laisk, Maire Peters, Merli Saare, Kadri Haller-Kikkatalo, Helle Karro, Andres Salumets10.1016/j.jri.2010.06.001Journal of Reproductive Immunology (2010)2010-06-21Journal of Reproductive Immunology2010-06-21http://www.jrijournal.org/article/PIIS0165037810001038/abstract?rss=yesAbstract: Studies in mice demonstrate that the maternal T cell repertoire is aware of paternal antigens during pregnancy, but in healthy pregnancy reactive T cells do not mediate anti-fetal immunity. Mice expressing transgenic T cell receptors (TCRs) specific for paternal and conceptus antigens are powerful tools for elucidating the events surrounding paternal antigen presentation to the maternal T cell repertoire, the nature of the ensuing T cell response and the factors that skew the response towards immune tolerance to allow survival and development of the conceptus. While results from different transgenic TCR models are not always consistent, there is now sufficient data to allow a consensus interpretation that maternal antigen presenting cells present initially seminal fluid antigens and later placenta-derived antigens to both the CD4+ and CD8+ T cell repertoire. T cell proliferation is generally followed by entry into a state of anergy demonstrated by decreased cytokine production and hyporesponsiveness upon restimulation. Some models also demonstrate downregulation of the TCR and co-stimulatory molecules, clonal deletion of paternal antigen-reactive T cells, or alternatively T cell ignorance of paternal antigens. This review will summarise the range of transgenic TCR studies that have shed light on the events surrounding paternal antigen presentation and the various T cell responses to insemination and pregnancy. The benefits, limitations and caveats of these models, and their impact upon data interpretation, are discussed.Utilising T cell receptor transgenic mice to define mechanisms of maternal T cell tolerance in pregnancy - Corrected ProofLachlan M. Moldenhauer, John D. Hayball, Sarah A. Robertson10.1016/j.jri.2010.05.007Journal of Reproductive Immunology (2010)2010-06-21Journal of Reproductive Immunology2010-06-21REVIEWhttp://www.jrijournal.org/article/PIIS0165037810001002/abstract?rss=yesAbstract: Experimental autoimmune orchitis (EAO) with experimental autoimmune epididymitis (EAE) can be induced in mice by immunization with testicular antigens emulsified in adjuvants. On immunization with syngeneic testicular germ cells (TGC) alone, EAO with no EAE is induced in mice. Recently, we found that EAE with no EAO can be induced in vasectomized mice by immunization with TGC. In the present study, we investigated the appearance of autoantigens relevant to EAO and EAE by reacting each immune serum sample with testes and epididymides extracts from normal mice of various ages by immunoblotting. The results showed that the antisera obtained from mice with EAO lesions specifically defined testicular antigens with molecular weights of 15kDa, 40kDa, 75kDa and >200kDa from 4 weeks of age, but the antisera obtained from mice with EAE strongly defined both testicular and epididymal antigens of 25kDa from 5 and 8 weeks of ages, respectively. These results suggest that vasectomy changes the target autoantigens in TGC-induced autoimmunity.Developmental ontogeny of autoantigens associated with localized autoimmunity in murine testis and epididymis - Corrected ProofNing Qu, Munekazu Naito, Hayato Terayama, Shuichi Hirai, Jun Li, Yuki Ogawa, Miyuki Kitaoka, Masahiro Itoh10.1016/j.jri.2010.05.005Journal of Reproductive Immunology (2010)2010-06-16Journal of Reproductive Immunology2010-06-16http://www.jrijournal.org/article/PIIS0165037810001014/abstract?rss=yesAbstract: Anti-paternal HLA-antibodies are considered a harmless phenomenon during most pregnancies, whereas their role in recurrent miscarriage (RM) patients is disputed. In contrast to primary RM, patients with secondary RM have carried a fetus to term pregnancy prior to a series of miscarriages, which increases the chance that allogeneic fetal cells appear in the maternal circulation. This study investigates the frequency of HLA-antibodies in secondary RM, primary RM patients and parous controls and analyzes whether the presence of HLA-antibodies in early pregnancy is associated with pregnancy outcome. Sera from women with secondary RM (n=56), primary RM (n=13) and parous controls (n=24) were tested for HLA-antibodies using an ELISA assay and complement dependent cytotoxicity. Samples were taken at gestational week 4–5 in 62 (90%) of the patients. HLA-antibodies were significantly more frequent in secondary RM patients with a boy prior to the miscarriages (62%) compared to secondary RM patients with a firstborn girl (29%, p=0.03), primary RM patients (23%, p=0.02) and parous controls (25%, p=0.005). Forty-one percent of HLA-antibody positive pregnant RM patients had a live birth compared to 76% of HLA-antibody negative RM patients, p=0.006 (adjusted OR: 0.22 (0.07–0.68), p=0.008). In conclusion, HLA-antibodies are significantly more frequent in secondary RM patients with a firstborn boy than in other RM patients and controls. The presence of these antibodies in early pregnancy is associated with a reduced chance of a live birth. Further exploring this association may increase our understanding of maternal acceptance of the fetal allograft.The presence of HLA-antibodies in recurrent miscarriage patients is associated with a reduced chance of a live birth - Corrected ProofHenriette Svarre Nielsen, Marian D. Witvliet, Rudi Steffensen, Geert W. Haasnoot, Els Goulmy, Ole Bjarne Christiansen, Frans Claas10.1016/j.jri.2010.05.006Journal of Reproductive Immunology (2010)2010-06-16Journal of Reproductive Immunology2010-06-16http://www.jrijournal.org/article/PIIS0165037810000999/abstract?rss=yesAbstract: This study investigated the serum concentration of soluble CD30 (sCD30) in pregnant women with isolated fetal intrauterine growth restriction, in pregnancies complicated by preeclampsia with and without accompanying intrauterine growth restriction, and in normotensive healthy pregnant controls. Lower serum concentrations of sCD30 were observed in the group of normotensive pregnant women with a growth-restricted fetus in comparison with the group of healthy pregnant controls, and also in comparison with both preeclamptic groups of pregnant women with and without fetal growth restriction. The concentration of sCD30 in maternal serum from preeclamptic women did not differ in comparison with values from healthy controls or pregnancies complicated by isolated fetal intrauterine growth restriction.Soluble CD30 in normotensive pregnant women with isolated fetal intrauterine growth restriction: a comparison with preeclamptic women - Corrected ProofMarzena Laskowska, Katarzyna Laskowska, Jan Oleszczuk10.1016/j.jri.2010.05.004Journal of Reproductive Immunology (2010)2010-06-15Journal of Reproductive Immunology2010-06-15SHORT COMMUNICATIONhttp://www.jrijournal.org/article/PIIS0165037810000987/abstract?rss=yesAbstract: G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G-CSF quantification, we compared follicular fluid G-CSF measurements made with two multiplexed microbead assays purchased from Bio-Rad Laboratories and R&D Systems, and a commercial G-CSF ELISA (R&D Systems). Individual follicular fluids (n=139) associated with transferred embryos were analysed to determine cytokine profile and the fate of each transferred embryo was recorded. The effect of multiplexing as well as comparison of the respective performances of the microbead assay with a flow cytometry assay was explored. Multivariable logistic regression analysis was performed and receiver operating characteristic (ROC) analysis was used to determine the performance and sensitivity/specificity of each method for individual follicular fluids. Covariate factors known to influence IVF outcome such as age, serum oestradiol and embryo score were systematically integrated in each analysis. The quantification of follicular fluid G-CSF using microbead assay methodologies, but not ELISA, yielded results showing the utility of follicular fluid G-CSF as a biomarker predictive of a successful delivery (Auroc: 0.77 [0.68–0.84] (p=0.003) and 0.75 [0.66–0.82] (p=0.004) for Bio-Rad and R&D Systems microbead assays respectively), whereas follicular fluid G-CSF values quantified by ELISA were not predictive (Auroc:0.61 [0.52–0.70] p=0.84). Microbead assay and flow cytometry appeared similarly efficient for quantifying follicular fluid G-CSF and multiplex versus single-plex assays did not influence the reliability of quantification.Performance evaluation of microbead and ELISA assays for follicular G-CSF: a non-invasive biomarker of oocyte developmental competence for embryo implantation - Corrected ProofNathalie Lédée, Carine Munaut, Valérie Sérazin, Sophie Perrier d’Hauterive, Letizia Lombardelli, Federica Logiodice, Robert Wainer, Virginie Gridelet, Gérard Chaouat, Francis Frankenne, Jean Michel Foidart, Marie-Pierre Piccinni10.1016/j.jri.2010.05.003Journal of Reproductive Immunology (2010)2010-06-14Journal of Reproductive Immunology2010-06-14http://www.jrijournal.org/article/PIIS0165037810000951/abstract?rss=yesAbstract: We investigated clot lysis time, thrombin activatable fibrinolysis inhibitor antigen (TAFI) levels and TAFI gene polymorphisms in pregnant patients with severe preeclampsia, with or without associated antiphospholipid syndrome (APS). The study groups included 82 pregnant patients without antiphospholipid antibodies with severe preeclampsia (PE group) and 10 pregnant APS patients who developed severe preeclampsia (APS-PE group). Controls included 76 primary pregnant APS patients (APS group) and 89 healthy pregnant patients (NOR group) with uneventful term pregnancy and delivery. Patients in the APS-PE, APS and NOR groups were sampled during each trimester of pregnancy and at 4–6 months and 12 months after delivery. Patients in the PE group were sampled during the third trimester and after delivery. Significantly prolonged clot lysis time after delivery was found in the PE, APS-PE and APS groups compared to the NOR group. The PE and APS-PE groups had longer clot lysis time than the APS group. Levels of TAFI were found to be higher after delivery in patients of the PE and APS-PE groups compared to the APS and NOR groups. Allele distribution of the TAFI gene polymorphisms was similar among the four study groups. We conclude that increased TAFI antigen levels and impaired fibrinolysis are pathogenetic factors in preeclampsia, regardless of whether or not preeclampsia is associated with the presence of antiphospholipid antibodies.Clot lysis time and thrombin activatable fibrinolysis inhibitor in severe preeclampsia with or without associated antiphospholipid antibodies - Corrected ProofM. Angeles Martínez-Zamora, Dolors Tassies, Francisco Carmona, Gerard Espinosa, Ricard Cervera, Juan Carlos Reverter, Juan Balasch10.1016/j.jri.2010.05.002Journal of Reproductive Immunology (2010)2010-06-10Journal of Reproductive Immunology2010-06-10http://www.jrijournal.org/article/PIIS016503781000094X/abstract?rss=yesAbstract: Endometriosis is a common gynaecological disease that is characterized and defined as the presence of endometrial tissue outside the uterus, causing painful periods and subfertility in approximately 10% of women. After more than 50 years of research, little is known about the mechanisms underlying the development and establishment of this condition. Animal models allow us to study the temporal sequence of events involved in disease establishment and progression. Also, because this disease occurs spontaneously only in humans and non-human primates and there are practical problems associated with studying the disease, animal models have been developed for the evaluation of endometriosis. This review describes the animal models for endometriosis that have been used to date, highlighting their importance for the investigation of disease mechanisms that would otherwise be more difficult to elucidate, and proposing new alternatives aimed at overcoming some of these limitations.Endometriosis research: animal models for the study of a complex disease - Corrected ProofIrene Tirado-González, Gabriela Barrientos, Nadja Tariverdian, Petra C. Arck, Mariana G. García, Burghard F. Klapp, Sandra M. Blois10.1016/j.jri.2010.05.001Journal of Reproductive Immunology (2010)2010-06-07Journal of Reproductive Immunology2010-06-07REVIEWhttp://www.jrijournal.org/article/PIIS0165037810000938/abstract?rss=yesAbstract: Cytokines are proposed to play roles in regulation of trophoblast invasion, spiral artery remodeling and immunoregulation during early pregnancy. Secretion of 12 cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, IFNγ, GM-CSF, MCP-1 and RANTES) by first trimester extravillous trophoblast and villous cytotrophoblast cells was examined using multiplex cytokine array technology. Seven (IL-1β, IL-8, IL-12p70, IL-13, GM-CSF, MCP-1 and RANTES) of the 12 cytokines examined were detectable in the samples studied (n=10 each group). Villous cytotrophoblast production of IL-1β and IL-8 increased with gestational age. Extravillous trophoblast production of IL-8, IL-13 and RANTES increased with gestational age. At 12–14 weeks gestation extravillous trophoblast cells secreted higher levels of IL-8, IL-13 and RANTES than villous cytotrophoblast cells.Secretion of cytokines by villous cytotrophoblast and extravillous trophoblast in the first trimester of human pregnancy - Corrected ProofKatsuhiko Naruse, Barbara A. Innes, Judith N. Bulmer, Stephen C. Robson, Roger F. Searle, Gendie E. Lash10.1016/j.jri.2010.04.004Journal of Reproductive Immunology (2010)2010-06-04Journal of Reproductive Immunology2010-06-04SHORT COMMUNICATIONhttp://www.jrijournal.org/article/PIIS0165037810000926/abstract?rss=yesAbstract: To determine the role of maternal immunity in protecting newborn mice against a Chlamydia trachomatis infection, female BALB/c mice were immunized intranasally (i.n.) with 104 inclusion forming units (IFU) of the C. trachomatis mouse pneumonitis biovar (MoPn). As a control, another group of female mice was sham-immunized i.n. with HeLa cell extracts. Immunized animals mounted strong immune responses as evidenced by high Chlamydia-specific antibody titers in serum and milk. Newborn mice born from immunized and sham-immunized dams were challenged i.n. with 103IFU of MoPn at two post-natal days (PND). Following inoculation, newborn mice were euthanized at 7- and 18-PND and the lungs, spleen and intestine were cultured for Chlamydia. Overall, no significant differences were observed between the mice born from and fed by immunized dams and mice born from and fed by sham-immunized dams. Of the mice born from immunized dams, 75 and 25% had positive lung cultures at 7- and 18-PND, respectively. Of the mice born from sham-immunized dams, 82 and 50% had positive lung cultures for those same days. When the number of IFU recovered from the lungs and spleens was compared between the two groups no significant differences were observed. However, when the number of IFU recovered from the small intestine was compared, significant differences were observed between the two groups of newborn mice (2×105 versus 32×106 at 7-PND and 9.2×106 versus 85×106 at 18-PND). In conclusion, maternal immunity plays a limited role in protecting newborn mice against a Chlamydia infection.Maternal immunity partially protects newborn mice against a Chlamydia trachomatis intranasal challenge - Corrected ProofSukumar Pal, Olga Tatarenkova, Luis M. de la Maza10.1016/j.jri.2010.04.003Journal of Reproductive Immunology (2010)2010-05-31Journal of Reproductive Immunology2010-05-31http://www.jrijournal.org/article/PIIS0165037804001251/abstract?rss=yesThis 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.WITHDRAWN: Effects of implantation and early pregnancy on the expression of cytokines and vascular surface molecules in the sheep endometrium - Corrected ProofAbu Nasar Md., Aminoor Rahman, Kenneth J. Snibson, Chee Seong Lee, Els N.T. Meeusen10.1016/j.jri.2004.08.006Journal of Reproductive Immunology (2009)2009-03-23Journal of Reproductive Immunology2009-03-23http://www.jrijournal.org/article/PIIS0165037807001714/abstract?rss=yesProgram - Uncorrected Proof10.1016/j.jri.2007.06.050Journal of Reproductive Immunology (2007)2007-07-09Journal of Reproductive Immunology2007-07-09