Journal of Reproductive Immunology RSS feed: Current Issue. Affiliated with the European Society of Reproductive Immunology 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/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. Journal of Reproductive Immunology0165-0378931January 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.jrijournal.org/article/PIIS0165037812000101/abstract?rss=yesEditorial Board10.1016/S0165-0378(12)00010-1Journal of Reproductive Immunology 93, 1 (2012)2012-01-01Journal of Reproductive Immunology2012-01-01931S0165-0378(12)X0002-0CO2CO2http://www.jrijournal.org/article/PIIS0165037811003238/abstract?rss=yesAbstract: The population explosion and unintended pregnancies, sexually transmitted diseases including human immunodeficiency virus, and cervical cancer, are major challenges to health worldwide. Their prevention might be achieved through vaccination-based approaches to activate specific immunity against pathogen- or fertility-associated antigens in the female genital tract (FGT). This article aims to review methodologies for enhancing adaptive immunity in the FGT to maximize the response to vaccination. Most components of the adaptive and innate mucosal immune system are present in the FGT and several features are common with the nasopharynx/bronchial and gastrointestinal tracts. In contrast to other mucosal sites, the FGT has minimal local lymphoid tissue. Other sites primarily produce IgA and IgM while in the FGT, especially the vaginocervix, IgG is the predominant immunoglobulin secreted. In rodents, data exist to substantiate a common mucosal immune system interconnecting the nasal/bronchial, gastrointestinal, and female genital tracts. The intranasal route seems the most efficacious to induce an immunity in the FGT especially when combined with a systemic or parenteral route. In humans, for induction of secretory IgA and IgG antibodies in the FGT, immunization by the nasal or the vaginal route is effective. In vaginal immunization, a strong and consistent antibody response is best achieved following vaccination during the follicular phase of the menstrual cycle. Antibodies administered systemically percolate into the FGT and can provide immunoprotection against target molecules or cells. Thus, as well as active immunization using selected routes, the passive immunization approach may provide a viable alternative to vaccinology for future development.Female genital tract immunity: distinct immunological challenges for vaccine developmentRajesh K. Naz10.1016/j.jri.2011.09.005Journal of Reproductive Immunology 93, 1 (2012)2011-12-05Journal of Reproductive Immunology2011-12-05931S0165-0378(12)X0002-0Basic Immunology18http://www.jrijournal.org/article/PIIS0165037811003305/abstract?rss=yesAbstract: Neurodevelopmental disorders may have their origins during intrauterine development. We used a well-defined animal model to test whether hematogenous infection with genital mycoplasma would alter the expression of genes associated with autism spectrum disorders (ASD). In a preliminary experiment, rats were exposed at 14 days gestation (GD14) to Mycoplasma pulmonis or sterile broth and sacrificed at GD18. Infection and inflammation status of the pups was ascertained by culture and cytokine ELISA. Intra-cardiac injection of 106CFU M. pulmonis resulted in amniotic infection of 100% of the pups and was accompanied by higher levels of IL-1β in amniotic fluids. In a second experiment, animals were infected in a similar manner but dams and their litters were sacrificed at GD18, GD21 or postpartum day 3 (PPD3). Expression of proinflammatory cytokines and neurodevelopmental genes in the fetal brains was evaluated. M. pulmonis infection significantly increased the expression of IL-1β, TNF-α and COX-2 in fetal and neonatal brains. Expression of GFAP and CD11b, markers for activation on astrocytes and microglial cells, respectively, was also increased for infected animals. M. pulmonis significantly increased SHANK-3 gene expression at GD21 and PPD3 and PCP-2 expression at GD21. No effect of M. pulmonis infection on Reelin, PTEN, BDNF or HGF was detected. These data suggest that M. pulmonis infection at GD14 increases the expression of proinflammatory genes in the perinatal brain. Further studies with earlier time-points of infection and ones that use behavioral outcomes are needed to better understand the potential role of genital mycoplasmosis on pychopathology.Effect of experimental genital mycoplasmosis on gene expression in the fetal brainAiyanna Burton, Oskar Kizhner, Mary B. Brown, Morgan R. Peltier10.1016/j.jri.2011.11.005Journal of Reproductive Immunology 93, 1 (2012)2011-12-19Journal of Reproductive Immunology2011-12-19931S0165-0378(12)X0002-0Basic Immunology916http://www.jrijournal.org/article/PIIS0165037811003299/abstract?rss=yesAbstract: Decidual cells are central to innate immunity at the maternal/fetal interface. We sought to characterize the response of decidual cells to stimulation and then removal of lipopolysaccharide (LPS) using a whole genome approach. Decidual cells were isolated from term unlabored cesarean sections. Cells were stimulated with LPS and RNA isolated both pre-stimulation and 2 and 24h post-stimulation. Media were changed and RNA extracted 48h later. Gene expression was measured using Agilent 44K whole genome microarrays. Data were visualized and interpreted using Ingenuity Pathway Analysis (IPA) software and selected (n=5) target gene expression was verified with quantitative real-time PCR. Genes related to immune function were up-regulated at 2 and 24h after LPS exposure and then generally returned to baseline or were at least substantially reduced after LPS removal. Pathway analysis also revealed that genes involved in lipid metabolism (specifically cholesterol and steroid biosynthesis), iron metabolism, and the plasminogen system were coordinately altered following exposure to LPS. Our novel, preliminary findings provide insight into possible mechanisms via which the host inflammatory response could contribute to preterm birth and warrant further investigation in preterm samples.Comprehensive analysis of the transcriptional response of human decidual cells to lipopolysaccharide stimulationKatherine P. Himes, Daniel Handley, Tianjiao Chu, Brian Burke, Kimberly Bunce, Hyagriv N. Simhan, David G. Peters10.1016/j.jri.2011.11.004Journal of Reproductive Immunology 93, 1 (2012)2011-12-14Journal of Reproductive Immunology2011-12-14931S0165-0378(12)X0002-0Basic Immunology1727http://www.jrijournal.org/article/PIIS0165037811003275/abstract?rss=yesAbstract: Knowledge on the regulation of corpus luteum (CL) function in the mare is scarce. In this study, the presence of cytokines tumor necrosis factor alpha (TNF) and interferon gamma (IFNG), and their receptors (TNFRI, TNFRII and IFNRI), was investigated in equine CL throughout the luteal phase. The effects of TNF and IFNG on secretory function and viability of luteal cells were defined in vitro. Cytokine ligands and receptors were present in steroidogenic and endothelial cells. Protein expression for TNF was greater in mid-phase and regressing CL, while TNFRI was increased in regressing CL and TNFRII did not change. IFNG and IFNRI showed the highest expression in regressing CL. Transcription of mRNA for TNF increased from mid-phase to regressing CL and both TNFRI and TNFRII decreased from early to regressing CL. Transcription of mRNA for IFNG was lower in CL from early phase than in mid or regressing luteal phase, while IFNRI expression was not changed. In the early CL, TNF acted to increase P4 and PGE2 but decrease PGF2α secretion. In the mid luteal phase, TNF increased PGF2α secretion and TNF+IFNG decreased PGE2 secretion. In the regressing luteal phase, TNF, IFNG and TNF+IFNG decreased P4 and PGE2 secretion, but TNF and TNF+IFNG increased PGF2α secretion by luteal cells. Cell viability was reduced by TNF+IFNG in regressing CL. These data show the presence of cytokines TNF and IFNG, and their receptors, in the equine CL and indicate their potential involvement in regulation of luteal function.Cytokines tumor necrosis factor-α and interferon-γ participate in modulation of the equine corpus luteum as autocrine and paracrine factorsA. Galvão, D.J. Skarzynski, A. Szóstek, E. Silva, A. Tramontano, A. Mollo, L. Mateus, G. Ferreira-Dias10.1016/j.jri.2011.11.002Journal of Reproductive Immunology 93, 1 (2012)2011-12-12Journal of Reproductive Immunology2011-12-12931S0165-0378(12)X0002-0Animal Studies2837http://www.jrijournal.org/article/PIIS0165037811003287/abstract?rss=yesAbstract: Recurrent embryo implantation failure (RIF) is a disorder with potentially devastating physiological and psychological manifestations for those affected. Although its prevalence is not uncommon, many of the mechanisms involved still require elucidation. Both organ-specific and systemic autoimmunity are associated with an increased prevalence of recurrent miscarriage and reproductive failure, rendering the role of the maternal immunological system in fertility a key concept. It is believed by some that central to this theme is the maternal cytokine profile, with particularly T-helper (Th) cells. Immune modulating therapies have therefore been mooted as potential therapeutic strategies. Recent reports of high pregnancy rates achievable in women with RIF have added fuel to the debate regarding the effectiveness of intralipid in modulating the immune system. We would like to assess if there is sufficient current evidence of acceptable quality to permit an assumption that intralipid therapy is an effective treatment for women undergoing repeated assisted reproduction cycles. We have concluded that appropriately controlled, large-scale, confirmatory studies are necessary to prove the efficacy of intralipid before it can be recommended for routine use.Intralipid therapy for recurrent implantation failure: new hope or false dawn?N. Shreeve, K. Sadek10.1016/j.jri.2011.11.003Journal of Reproductive Immunology 93, 1 (2012)2011-12-12Journal of Reproductive Immunology2011-12-12931S0165-0378(12)X0002-0Clinical Science3840http://www.jrijournal.org/article/PIIS0165037811003251/abstract?rss=yesAbstract: Recurrent miscarriage (RM) without an obvious identifiable cause may arise from excessive maternal T and natural killer (NK) cell activity against the trophoblast or early embryo. Impaired regulatory T cell function leading to increased pro-inflammatory Th17 and NK cell cytotoxicity may be central. Ongoing subclinical endometrial infection and/or inflammation with increased secretion of TNFα and stimulation of autoimmunity to heat shock proteins may also be contributory. Therapies with a varying theoretical basis and clinical evidence aimed at reducing excessive endometrial immune activity have been used non-selectively in women with RM with variable success. Recent work has now improved our understanding of the role of the different immune cells and proteins that are important at each stage of a normal pregnancy. The vulnerability of the early embryo to T and NK cell-mediated rejection suggests that immune-based therapies need to be maximally effective during early pregnancy. Targeting RM women with demonstrable T and NK cell activity may improve the overall clinical efficacy of these treatments. It may also prevent costly and possibly harmful use in women who are unlikely to respond, and make better use of scarce resources. This report describes the underlying principles behind the use of the different immune-based therapies. The broad evidence supporting their efficacy is also described, as are the possible adverse consequences. Suggestions are also made on how the maternal immune system may be positively modulated using current, widely available treatments that have minimal or no side effects.The basis and value of currently used immunomodulatory therapies in recurrent miscarriageA.S. Bansal, B. Bajardeen, M.Y. Thum10.1016/j.jri.2011.10.002Journal of Reproductive Immunology 93, 1 (2012)2011-12-05Journal of Reproductive Immunology2011-12-05931S0165-0378(12)X0002-0Clinical Science4151http://www.jrijournal.org/article/PIIS0165037811003263/abstract?rss=yesAbstract: An explanation is needed for why some men and women show positive in hCG screening tests when they are not pregnant, do not have cancer and are otherwise asymptomatic. In this study, a total of 10 families comprising 30 persons with a history of positive hCG tests were investigated. Total hCG was measured in serum and urine samples using the Siemens Immulite hCG test. Total hCG, C-terminal peptide determinant, and hCGβ were measured in 96 well plate assays. Twenty-four of 30 family members produced only hCGβ, and hCG or hCGβ missing the β-subunit C-terminal peptide, two rarely detected hCG degradation products as the only source of hCG immunoreactivity. In every one of the 10 families, hCG related molecules were detected first in one member and then later detected in other family members. In 8 of 10 families, all members produced comparable hCG concentration (Cases 1–8). All of the 10 original family members investigated were otherwise asymptomatic, and tested negative in ordered head and pelvis MRI scans and CT chest cancer tests. None had been administered hCG for dietary, anabolic or fertility reasons. Therefore Familial hCG Syndrome, a genetic defect, was indicated in each of the 10 families. In these cases of Familial hCG Syndrome only biologically inactive variants of hCG were detected. It is inferred that in Familial hCG Syndrome, hCG gene expression does not interfere with fertility.Familial hCG SyndromeLaurence A. Cole10.1016/j.jri.2011.11.001Journal of Reproductive Immunology 93, 1 (2012)2011-12-08Journal of Reproductive Immunology2011-12-08931S0165-0378(12)X0002-0Clinical Science5257http://www.jrijournal.org/article/PIIS0165037811003317/abstract?rss=yesAbstract: Adenomyosis, a condition usually associated with multiparity, is not generally seen as a cause of infertility. However, recent studies have reported a reduction in IVF implantation rates and a link with miscarriage, suggesting that adenomyosis may interfere with successful implantation. To investigate this hypothesis, the clinical records and laboratory results, which routinely include immunohistochemical examination of a late luteal phase endometrial biopsy for leukocytes, were retrospectively reviewed for 64 women with implantation failure and who previously had been screened for the presence of adenomyosis by pelvic MRI.The presence of either diffuse or “adenomyoma” type of adenomyosis was associated with a marked increase (p=0.004) in the density of macrophages and natural killer cells in the endometrial stroma, compared to those women with mild focal adenomyosis or no disease. These findings point to an immunological mechanism by which adenomyosis might interfere with successful embryo implantation.The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. II: adenomyosis and macrophagesKelton P. Tremellen, Peter Russell10.1016/j.jri.2011.12.001Journal of Reproductive Immunology 93, 1 (2012)2011-12-22Journal of Reproductive Immunology2011-12-22931S0165-0378(12)X0002-0Clinical Science5863http://www.jrijournal.org/article/PIIS016503781100324X/abstract?rss=yesAbstract: Intrauterine growth restriction (IUGR) and/or neonatal low birth weight are often associated with increased intima/media thickness of the abdominal aortic wall (aIMT). Several studies in children suggested that aIMT might be related to inflammation, probably indicating an early stage of adulthood diseases, such as atherosclerosis. Our previous study performed on the abdominal aortic wall of a stillbirth presenting with IUGR and aIMT suggested an association among IUGR, aIMT, and inflammation, also highlighting the presence of fibroblastoid cells, which are thought to represent peculiar elements of the pre-atherosclerotic lesions. These observations led us to analyze two cytokines involved in the inflammation cascade, IL-1β and IL-23, in amniotic fluid samples of IUGR fetuses and small-for-gestational-age newborns presenting with aIMT and in normal controls. Our results indicate that IL-23, but not IL-1β, concentrations differed in the groups analyzed. Therefore, IL-23, a regulatory element that bridges the innate and adaptive arms of the immune system, might be involved in the inflammatory process observed in fetal aIMT.IL-1β and IL-23 in amniotic fluids of ultrasound-detected aortic intima/media thickness and growth retardationVincenza Rita Lo Vasco, Erich Cosmi, Silvia Visentin, Tania Di Raimo, Roberto Salmaso, Vincenzo Zanardo, Daniele Trevisanuto, Rita Businaro10.1016/j.jri.2011.10.001Journal of Reproductive Immunology 93, 1 (2012)2011-12-05Journal of Reproductive Immunology2011-12-05931S0165-0378(12)X0002-0Clinical Science6467