Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary.
Problem: CD160, a cell surface co-receptor, is capable of up- or downregulating cell proliferation, cytotoxicity or cytokine production on lymphocytes. Our aim was to investigate CD160(+) lymphocytes in the periphery and at the maternal-foetal interface during murine pregnancy.
Method Of Study: CD4(+) , CD8(+) and gamma/delta T-cell phenotype, TIM3 co-expression and cytotoxic activity of CD160(+) lymphocytes of pregnant BALB/c mice were analysed by flow cytometry. Read More
Division of Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Problem: Effective therapy for endometrial receptivity of patients with repeated embryo implantation failure (RIF) is far undeveloped. Whether intrauterine perfusion of dexamethasone (DXM), local administration of drugs with less systematic side-effects, benefit for embryo implantation by suppressing uterine NK (uNK) cells to improve endometrial receptivity remains unknown.
Method Of Study: Women with RIF were analyzed for the correlation between the percentage of uNK cells during implantation window and following clinical pregnancy rate to determine the appropriate range of uNK for embryo implantation. Read More
Problem: In endocervical epithelial cells (End1/E6E7), miRNA let-7f plays an important role in the control of innate immunity. The underlying molecular mechanism for let-7f regulation in these cells remains largely unclear.
Methods Of Study: let-7f was knocked down in End1/E6E7 cells using siRNA, and differential gene expression was analyzed by microarray. Read More
Problem: The role of extracellular signal-regulated kinase (ERK)1/2-mediated angiogenesis during endometriotic nidation is unknown. We posit that ERK1/2-induced angioblast differentiation and proliferation promotes ectopic endometrial angiogenesis.
Methods Of Study: Human eutopic and ectopic endometria were immunostained for total- (T-) or phosphorylated- (P-) ERK1/2 or double-immunostained for P-ERK1/2-CD34 and PCNA-CD34. Read More
Faculty of Medicine, Benha University, Benha, Egypt.
Problem: Little is known about how preeclampsia affects regulatory T-cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4(+) CD25(high) FOXP3(+) , CD4(+) CD25(low) FOXP3(+) , and CD4(+) FOXP3(+) Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia.
Method Of Study: The percentage of umbilical cord blood CD4(+) CD25(high) FOXP3(+) , CD4(+) CD25(low) FOXP3(+) , and CD4(+) FOXP3(+) Tregs were analyzed by flow cytometry. Read More
Division of Rheumatology, University of Pavia, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
Undifferentiated connective tissue diseases (UCTDs) are a heterogeneous group of disorders characterized by symptoms and signs suggestive of systemic autoimmune rheumatic disease (ARD), but which do not fulfill all the established criteria for definite diagnosis of a condition. Although a third of UCTDs can progress to a definite ARD within months or years, most UCTDs can remain stable for years with minimal disease activity. The annual incidence of UCTD in the general population ranges from 14 to 140 per 100 000 people. Read More
Problem: Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection worldwide and known to increase the risk for HIV acquisition. Few studies have investigated how infection of epithelial cells compromises barrier integrity and antimicrobial response.
Method Of Study: ECC-1 cells, a human uterine epithelial cell line, were treated with live and heat-killed C. Read More
Am J Reprod Immunol 2017 Aug 30. Epub 2017 Aug 30.
Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.
Problem: The level of CCL19 increased in the peritoneal fluid of women with endometriosis, but the precise mechanism of CCL19/CCR7 in the pathogenesis of endometriosis remains unknown.
Methods: ELISA and immunohistochemistry were performed to analyze CCL19/CCR7 expressions in peritoneal fluid and endometrium from women with endometriosis (n = 38) and controls (n = 32). Cell proliferation and transwell invasion assays were applied to detect proliferation and invasion of human endometrial stromal cells (ESCs). Read More
Problem: The purpose of this study was to explore whether vitamin D might be a marker of female primary infertility in association with the presence of autoimmune diseases (ADs).
Methods: The study was a cross-sectional descriptive study in consecutive outpatients of the Polymedical Center for Prevention of Recurrent Spontaneous Abortion (RSA), in Rome, Italy. Women were eligible if they received a diagnosis of primary infertility or RSA. Read More
Problem: In molecular analysis of tissue biopsy specimens, one crucial aspect is characterization of immune cell populations. This is especially important for evaluation of uterine receptivity by assessing levels of lymphocyte populations including CD56(bright) CD16- uterine NK cells and CD56(dim) CD16+ conventional NK cells. Our objective was to investigate whether measuring total RNA transcripts from a tissue specimen would accurately reflect immune cell levels and be a new technique to assess immune cell subsets. Read More
Problem: Mucosal vaccines have long been sought after to improve protection though the production of both a mucosal and systemic immune response, and are thought to be particularly effective at the site of induction. Development of such vaccines has, however, been delayed by the general propensity to develop immune tolerance to antigens encountered at mucosal sites. This study aimed to determine whether an appropriately formulated subunit vaccine delivered to the uterine lumen would effectively trigger induction of immunity over tolerance. Read More
Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.
Problem: The effectiveness of progesterone (P4) treatment for preventing preterm births is unclear. Its effects on the uterine cervix were tested using cultured human uterine cervical fibroblasts (UCFs).
Method Of Study: UCFs were incubated with lipopolysaccharide (LPS) in the presence or absence of P4 under various conditions. Read More
Problem: Placental pericytes are essential for placental microvascular function, stability, and integrity. Mechanisms of human cytomegalovirus (HCMV) pathogenesis incorporating placental pericytes are unknown.
Method Of Study: HCMV-infected placental tissue was stained by dual-labeled immunohistochemistry. Read More
Problem: Neutrophils are capable of performing phagocytosis, a primary mechanism for microbial killing. Intra-amniotic infection is characterized by an influx of neutrophils into the amniotic cavity. Herein, we investigated whether amniotic fluid neutrophils could phagocytize bacteria found in the amniotic cavity of women with intra-amniotic infection. Read More
Problem: Placental dysfunction is present over 50% of cases of stillbirth and fetal growth restriction (FGR). Villitis of unknown etiology (VUE), an inflammatory condition of the placenta characterized by maternal T cell infiltrates in the villous stroma and dysregulation of inflammatory cytokines, is more frequent in FGR and stillbirth.
Method Of Study: A novel in vitro model of placental inflammation was developed to test the hypothesis that inflammatory cells seen in VUE and/or cytokines impair placental function. Read More
Problem: Inflammation is a key process in the establishment and progression of endometriosis. Resistin, an adipocytokine, has biological properties linked to immunologic functions, but its role in endometriosis is unclear.
Method Of Study: Resistin gene expression was examined in eutopic and ectopic endometrial tissues from women with (n=25) or without (n=25) endometriosis. Read More
Problem: Preeclampsia (PE) is associated with inflammation and decreased Treg cells and IL-10. The reduced uterine perfusion pressure (RUPP) rat model of PE exhibits these characteristics, and we hypothesized that induction of endogenous Tregs by a specific stimulus (CD28 superagonistic monoclonal antibody) would reduce inflammation, vasoactive factors, and hypertension in RUPP rats.
Method Of Study: RUPP was performed at gestation day (GD) 14; CD28 superagonist was administered intraperitoneally GD15; GD18 carotid catheters were inserted, and GD19 MAP and pup weight, blood, and tissues were collected. Read More
Problem: To evaluate the role of regulatory T (Treg) cells in autoimmune ovarian disease (AOD).
Method Of Study: AOD model was set up by thymectomy of BALB/C mice on day 3 (d3tx). The variation of T lymphocyte subsets, especially the Treg cells were analyzed in the peripheral blood, spleen, para-aortic, and inguinal lymph nodes in d3tx mice. Read More
Pregnancy is an evolutionarily important and mysterious process. The placenta, as the nutrient and gas exchange organ, plays an essential role during this process. In addition, the interaction between trophoblast and maternal immune cells at the maternal-fetal interface is also associated with successful pregnancy. Read More
Problem: It is unclear if the immunologic alterations induced by pregnancy could persist.
Method Of Study: Antenatal rubella sero-negativity was correlated with gravidity, abortions and parity in 112 083 gravidae managed during 1997-2015, with further analysis stratified for factors known to influence rubella serology.
Problem: Immune tolerance with respect to a semi-allogeneic fetus plays a key role in the establishment of a pregnancy. Memory T follicular helper (Tfh) cells have a central role in the regulation of the adaptive immune response. Much of our knowledge of memory Tfh cells' function comes from immune-related diseases. Read More
Problem: Uterine natural killer (uNK) cells are major players during implantation and early pregnancy. The aim of our study was to analyze uNK cell concentration in the endometrium of idiopathic recurrent miscarriage (iRM) patients and fertile controls.
Method Of Study: Out of n=130 couples with ≥3 consecutive, clinical RM screened according to a standardized diagnostic protocol, n=58 patients with iRM were identified. Read More
Problem: Levels of placental growth factor (PlGF) peak during third trimester of pregnancy, a time when women are at increased risk of virus-induced morbidity. We hypothesized PlGF might contribute to an exaggerated inflammatory response to Toll-like receptor (TLR) activation.
Method Of Study: Primary human adult and cord blood CD14(+) cells were cultured in the presence of TLR ligands and/or PlGF. Read More
Problem: The aim of this prospective study was to investigate the prevalence of chronic endometritis (CE) in infertile women with a history of repeated implantation failure (RIF) and to determine whether oral antibiotic treatment improves their live birth rate in the following embryo transfer (ET) cycles.
Method Of Study: Endometrial biopsy samples obtained from infertile women with RIF were subjected to immunohistochemistrical/histopathologic diagnosis of CE. Following antibiotic administration to the RIF/CE group, their histopathologic cure rate, microbial detection rate, and reproductive outcome in the subsequent ET cycles were prospectively studied. Read More
Problem: The use of in vitro maturation (IVM) as an alternative approach to the conventional assisted reproductive technique in clinical practice is limited due to low fertilization rate. The expression of Toll-like receptors (TLRs) as members of an innate immune system in cumulus cells are thought to affect fertilization. This study was aimed to evaluate the effect of IVM on TLR4 gene expression and fertilization rate in oocytes derived from IVM in comparison with in vivo matured one. Read More
Problem: CEACAM1 and CEACAM6 belong to the carcinoembryonic antigen (CEA) family and may play an immune-modulatory role during pregnancy. The aim of the study was to determine the blood serum levels of soluble CEACAM1 and CEACAM6 over the course of pregnancy and postpartum.
Method Of Study: CEACAM1 and CEACAM6 levels were determined with customized in-house Sandwich-enzyme-linked immunosorbent assay (ELISA) systems. Read More
Problem: APOBEC3G (A3G) is a cytidine deaminase that exhibits antiviral activity by introducing C-to-T hypermutation in viral DNA. We recently observed the distinct presence of C-to-T hypermutation of human papillomavirus DNA in uterine cervical intraepithelial neoplasia (CIN), suggesting the possible involvement of A3G in the mutation-inducing process. Consequently, we investigated the association of A3G expression with CIN progression in this study. Read More
The PD-1/PD-L1 pathway plays a vital role in the maintenance of peripheral tolerance, promoting the development and function of regulatory T cells, and maintaining the quiescence of autoreactive T cells. Abnormalities in this inhibitory pathway are involved in the pathogenesis of some disorders such as tumours, autoimmune diseases, pregnancy complications, and transplantation rejection. Immune privilege represents a special immunological condition, where foreign antigens can be tolerated and do not elicit an immune response. Read More
The well-established classic role of vitamin D is implicated in the regulation of the balance between calcium and phosphorus. Furthermore, vitamin D is also involved in many non-classic physiological processes, mainly including the regulation of cell proliferation, differentiation, apoptosis and immune function, participation in the inflammatory response and maintenance of genome stability function. During pregnancy, vitamin D receptor and its metabolic enzymes are expressed at the placenta and decidua, indicating the potential role in the mechanism of immunomodulation at the maternal-fetal interface. Read More
Problem: The presence of dendritic cells (DCs) and associated cytokines in follicular fluid (FF) from patients with polycystic ovary syndrome (PCOS) remains unknown.
Methods Of Study: FF was collected from PCOS patients and patients with severe male factor infertility (control) at the day of transvaginal oocyte retrieval. Phenotypes of DC were detected by flow cytometry, and TNF-α, IL-6, IL-10, and IL-23 were assessed by ELISA. Read More
Am J Reprod Immunol 2017 Sep 6;78(3). Epub 2017 Jun 6.
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
Problem: To characterize the amniotic fluid (AF) inflammatory-related protein (IRP) network in patients with a sonographic short cervix (SCx) and to determine its relation to early preterm delivery (ePTD).
Method Of Study: A retrospective cohort study included women with a SCx (≤25 mm; n=223) who had amniocentesis and were classified according to gestational age (GA) at diagnosis and delivery (ePTD <32 weeks of gestation).
Results: (i) In women with a SCx ≤ 22 1/7 weeks, the concentration of most IRPs increased as the cervix shortened; those with ePTD had a higher rate of increase in MIP-1α, MCP-1, and IL-6 concentrations than those delivering later; and (ii) the concentration of most IRPs and the correlation between several IRP pairs were higher in the ePTD group than for those delivering later. Read More
During normal pregnancy, the mechanism by which the fetus escapes immunological rejection by the maternal womb remains elusive. Given the biological complexities, the immunological mechanism is unlikely to be simply an allograft response in acceptance or rejection of the early pregnancy. Circadian clock responsible for the mammalian circadian rhythm is an endogenously generated rhythm associated with almost all physiological processes including reproduction. Read More
Problem: Influenza infection severity may be mediated by estradiol and/or progesterone.
Method Of Study: An exploratory study was designed to evaluate 17-β-estradiol and progesterone on influenza infection and examine immune-mediated response in a mouse model. Inoculation with placebo or mouse-adapted H1N1 influenza virus occurred. Read More
Problem: This study explored the possibility of evaluating cervical maturation using swabbed cervical cell samples at term pregnancy, and aimed to develop a novel approach to predict labor onset.
Method Of Study: Women with uncomplicated pregnancies (n=117 from 62 women at term pregnancy) were recruited. Messenger RNA expression levels of cervical cells for ten genes were quantified by qPCR. Read More
Am J Reprod Immunol 2017 Jul 19;78(1). Epub 2017 May 19.
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.
Problem: To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM).
Method Of Study: This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay. Read More
Problem: In chronic hepatitis B (CHB) carriers, alanine transaminase (ALT) flares are common in the peripartum period. There are limited data on immunological changes of pregnancy in CHB. We hypothesize that in pregnant CHB carriers, the Th1/Th2 cytokine ratio is altered resulting in changes in biochemical/virological and liver fibrosis markers. Read More
Problem: To define a more precise parameter for a better understanding of natural killer (NK) cells and its relation with regulatory T cells (Tregs) in women with recurrent implantation failure (RIF).
Method Of Study: The percentages of CD56+ cells, CD57+ cells and Foxp3+ cells in the endometrium and blood from 23 normal controls and 32 women with RIF were measured by immunocytochemistry and flow cytometry.
Results: Women with RIF had significantly increased ratio of CD57+ cells to CD56+ cells in both the endometrium (P<. Read More
Am J Reprod Immunol 2017 Aug 15;78(2). Epub 2017 May 15.
Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
CD8(+) T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal-maternal interface, but data on the amount of peripheral CD8(+) T cells and their functions during the window of implantation in recurrent implantation failure (RIF) patients are limited. Peripheral blood was obtained from 56 women with RIF and 16 fertile women in the mid-luteal phase of the menstrual cycle, and the CD8(+) T cells were determined by FACS analysis. No statistical differences in the proportion of peripheral CD8(+) T cells were observed among the women with RIF and the control group. Read More
Problem: To explore whether cervical carcinoma cell-derived interleukin-27 (IL-27) modulates the angiogenesis of vascular endothelial cells.
Method Of Study: The expression of IL-27 in cervical cancer tissues and cervical cell lines was analyzed by immunohistochemistry, ELISA and flow cytometry. Then, the effects of IL-27 on the proliferation and apoptosis-related molecules and angiogenesis in vitro of human umbilical vein endothelial cells (HUVECs) were investigated. Read More
Problem: To compare placental protein 13 (PP13) levels in the serum of women with primary postpartum hemorrhage (PPH) with a control population.
Methods: A prospective cohort study was conducted between May 2014 and May 2016 and included 435 pregnant women at term (38 weeks gestation) without any known risk factor and with normal labor. Multiples of median (MoM) were used to evaluate differences of the PP13 values between cases and controls. Read More