Abstract：
:Miscarriages in patients with antiphospholipid (aPL) antibodies have been attributed to thrombosis of placental vessels. However, we have shown that inflammation plays a crucial role in fetal injury. We identified tissue factor (TF), the major cellular activator of the coagulation cascade, as a key mediator in inflammation and fetal injury in aPL antibody-treated mice. We found that TF in maternal neutrophils was associated with fetal injury. TF expression in neutrophils contributes to the respiratory burst and subsequent trophoblast oxidative injury and pregnancy loss induced by aPL antibodies. We also analysed how TF contributes to neutrophil activation and trophoblast injury in this model. We showed that neutrophils from aPL antibody-treated mice express protease activated receptor 2 (PAR-2) and that stimulation of this receptor leads to neutrophil activation, trophoblast injury and fetal death. Mice deficient in PAR-2 and treated with aPL antibodies exhibited reduced neutrophil activation and normal pregnancies, indicating that PAR-2 plays an important role in the pathogenesis of aPL antibody-induced fetal injury. In addition, we demonstrated that the statins simvastatin and pravastatin downregulate TF and PAR-2 expression in neutrophils and thus prevent pregnancy loss. In summary, this study shows that TF signaling through PAR-2 mediates neutrophil activation and fetal death in antiphospholipid syndrome, and that statins may be an appropriate treatment for women with aPL antibody-induced pregnancy complications.
journal_name
J Reprod Immunoljournal_title
Journal of reproductive immunologyauthors
Girardi Gdoi
10.1016/j.jri.2009.03.003subject
Has Abstractpub_date
2009-11-01 00:00:00pages
126-31issue
2eissn
0165-0378issn
1872-7603pii
S0165-0378(09)00092-8journal_volume
82pub_type
杂志文章abstract：:Previous studies in our laboratory indicated that immunization of male and female Wistar and Lewis rats with epididymal protein DE, resulted in the development of anti-DE antibodies in over 90% of the animals, with a significant and reversible reduction of fertility. In the present study, ELISA assays performed to ana...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(95)00927-d
更新日期：1995-05-01 00:00:00
abstract：:Female CBA/J (H-2k) mice mated with male DBA/2J (H-2d) mice show a high level of fetal resorption, which can be reduced by immunization with BALB/c (H-2d) spleen cells. The morphologically defined fetal resorption rate upon which evaluation of the outcome of pregnancy has previously been based in this strain combinati...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(89)90036-3
更新日期：1989-05-01 00:00:00
abstract：:A large clinical literature suggests that estradiol (E(2)) plays a critical role in immune function. To further explore the relationship between E(2) and immune function, we examined a variety of immunological parameters in a rhesus monkey model of menopause and hormone replacement therapy. Rhesus monkeys (Age, 13.7+/...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/s0165-0378(00)00087-5
更新日期：2001-04-01 00:00:00
abstract：:Antisera to Mason-Pfizer or Baboon Endogenous Virus possessed complement-dependent cytotoxicity for cell lines chronically infected with these viruses, with some degree of cross-reaction. When appropriately absorbed with virus-free cells, the antisera were not cytotoxic for lymphocytes of adult males but lysed lymphoc...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(81)90001-2
更新日期：1981-03-01 00:00:00
abstract：:In oocyte donation (OD) pregnancies, a fetus is a complete allograft to the maternal host and OD pregnancies are an independent risk factor for preeclampsia. Immunocompetent cells contribute to spiral artery remodeling and the failure of this process could contribute to the pathophysiology of preeclampsia. Recent data...
journal_title：Journal of reproductive immunology
pub_type： 临床试验,杂志文章
doi：10.1016/j.jri.2015.07.005
更新日期：2016-04-01 00:00:00
abstract：:Endometriosis is a prevalent gynaecological disorder with a still unclear pathogenesis. So far inflammatory mechanisms are associated with disease progression and critical reviews have discussed the so-called 'danger theory' related to endometriosis. Hence, we performed immunoassays to evaluate whether local inflammat...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/j.jri.2018.07.006
更新日期：2018-11-01 00:00:00
abstract：:Menstrual toxic shock syndrome (mTSS) is an acute systemic inflammatory disease associated with the superantigenic exotoxin, toxic shock syndrome toxin (TSST)-1, produced by Staphylococcus aureus and the use of high absorbency tampons. Even though S. aureus is capable of elaborating several other superantigenic exotox...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/j.jri.2006.06.007
更新日期：2007-02-01 00:00:00
abstract：:Sperm antigens are being sought for the development of prototype contraceptive vaccines. For vaccine-induced antisperm antibodies to inhibit the function of viable sperm, target antigens must be expressed on the sperm surface before, during or after the acrosome reaction. The purpose of this study was to develop an ap...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(91)90019-m
更新日期：1991-05-01 00:00:00
abstract：:Substrains of BALB/c mice differ in their susceptibility to experimental autoimmune orchitis (EAO), with BALB/cJ representative of the non-responders and BALB/cBy representative of the responders. We examined whether the susceptibility of these two substrains could be altered by reciprocal adoptive transfer of lymphoi...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(90)90047-a
更新日期：1990-10-01 00:00:00
abstract：:The inhibitory effect of antilymphocyte globulin on spontaneous rosette formation by peripheral blood T cells between 10 and 21 weeks gestation was examined. No evidence was obtained from either a cross-sectional or a longitudinal study that increased rosette inhibition levels occur during early human pregnancy. Compa...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(80)90039-x
更新日期：1980-12-01 00:00:00
abstract：:During the past 40 years, polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants and nearly all women have some level of exposure. PBDEs have been isolated from amniotic fluid and cord plasma indicating vertical transmission; however, their effects on pregnancy outcome are largely unknown. Th...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/j.jri.2014.11.002
更新日期：2015-02-01 00:00:00
abstract：:In this review, we summarize the results of a number of our recent in vitro and in vivo experiments demonstrating that, in addition to the immunoregulatory functions, soluble HLA-G molecules also affect endothelial cell activity. We have found that soluble HLA-G1 (also designated HLA-G5) inhibits endothelial cell prol...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章,评审
doi：10.1016/j.jri.2007.03.007
更新日期：2007-12-01 00:00:00
abstract：:To analyze immunomodulating effects related to parity status, we studied trophoblast invasion grade, placental expression and systemic concentration of VEGF and its receptor Flt-1 in normal fertile (CBA/JxBALB/c) mice and abortion-prone (CBA/JxDBA/2) H-2(d)xH-2(k) mice. BALB/c or DBA/2 mated CBA/J females were, respec...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/j.jri.2010.03.004
更新日期：2010-06-01 00:00:00
abstract：:It is self-evident that infection and inflammation in the reproductive tract can inhibit male fertility, but the observation that fertility may also be compromised by systemic inflammation and disease is more difficult to explain. Recent studies implicating microbial pattern-recognition receptors, such as the Toll-lik...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/j.jri.2011.01.010
更新日期：2011-03-01 00:00:00
abstract：:Various ELISA methods have been applied by different research centers to test the efficiency of this approach for the diagnosis of sperm-immune infertility cases. The antigens used were either whole spermatozoa or solubilized spermatozoal membrane preparations and were immobilized on microtiter plates, except in one c...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(85)90004-x
更新日期：1985-12-01 00:00:00
abstract：:The levels of rabbit alpha-foetoprotein (RAFP) in foetal serum, neonatal serum and amniotic fluid during gestation have been evaluated by quantitative radial immunodiffusion. RAFP attained its peak concentration on the 24th day of pregnancy in foetal serum, while in amniotic fluid peaks were observed on ;the 14th and...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(80)90026-1
更新日期：1980-11-01 00:00:00
abstract：BACKGROUND:Elongation factor Tu GTP binding domain containing 2 (EFTUD2) is an alternative splicing factor that modulates cell differentiation and activation processes. EFTUD2 is known to modulate immune responses and mutation of the EFTUD2-gene lead to fetal malformation. Little is known about its expression and role ...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/j.jri.2020.103149
更新日期：2020-08-01 00:00:00
abstract：:Autologous anti-horseradish peroxidase antibody has been localized in pregnant rats at various levels through placental membranes en passage to fetal circulation. The antibody was complexed in situ with the antigen and the resulting complex was made visible electron microscopically by immunohistochemical techniques. V...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(85)90057-9
更新日期：1985-05-01 00:00:00
abstract：:Phytohaemagglutinin (PHA) was employed to study the constituents of the cell membrane in X- and Y-bearing human spermatozoa. The presence of certain receptors for PHA was revealed in the equatorial region of about 50% of the spermatozoa. To determine the association of the equatorial staining by PHA with one of the su...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(81)90005-x
更新日期：1981-03-01 00:00:00
abstract：:Preeclampsia has been recognized for at least 100 years. In the last 20 years, the consideration of the disorder as more than simply hypertension in pregnancy has led to an explosion in knowledge about preeclampsia pathophysiology. It is now evident that for most cases of preeclampsia, the root cause is the placenta. ...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章,评审
doi：10.1016/j.jri.2013.05.003
更新日期：2013-09-01 00:00:00
abstract：:The presence of a local immunosuppressive environment in the vicinity of the developing fetus has been suggested to explain survival of the semi-allogeneic fetus in a potentially hostile maternal immunologic environment. The presence of nonspecific suppressor cells in the uterus of pregnant mice has been well-document...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(90)90006-r
更新日期：1990-06-01 00:00:00
abstract：:The syndrome of preeclampsia has previously been ascribed to generalized maternal endothelial dysfunction, poor placentation and excessive maternal inflammatory response. Recent reports suggest that preeclampsia is associated with a Th1 predominant profile and may be considered as a failure of the tolerance system all...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章,评审
doi：10.1016/s0165-0378(03)00045-7
更新日期：2003-08-01 00:00:00
abstract：:A maternal low-protein (LP) diet in Sprague-Dawley rats results in low birth weight, rapid adipose tissue catch-up growth, adult obesity, and insulin resistance. The placenta functions to fulfill the fetus' nutrient demands. Adequate angiogenic factor concentrations help to ensure normal growth and vasculature develop...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/j.jri.2016.08.009
更新日期：2016-11-01 00:00:00
abstract：:In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cyt...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章,评审
doi：10.1016/j.jri.2014.02.005
更新日期：2014-10-01 00:00:00
abstract：:The debate about the presence of HIV-1 particles in human gametes and recent experimental results are reported in detail. Using immunocytochemistry, in situ hybridization at electron microscopy level, polymerase chain reaction and in vitro fertilization, it has been demonstrated that human spermatozoa can incorporate ...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章,评审
doi：10.1016/s0165-0378(98)00048-5
更新日期：1998-12-01 00:00:00
abstract：OBJECTIVE:Repeated implantation failure (RIF) has been shown related to maternal immune imbalance. Many studies suggested that prednisone promoted the Th17/Treg balance shift to the direction of immune tolerance. Our study aimed to evaluate the role of prednisone in Th17/Treg balance and pregnancy outcome in RIF patien...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/j.jri.2020.103245
更新日期：2021-02-01 00:00:00
abstract：:The rabbit sperm membrane autoantigen, RSA-1, has been isolated from the kidneys of bilaterally vasectomized rabbits. Using detergent extraction the IgG-RSA-1 complex in the kidney was isolated first on an anti-IgG immunocolumn. The eluted IgG-RSA-1 complex was then applied to an anti-sperm autoantibody column which b...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(84)90006-8
更新日期：1984-02-01 00:00:00
abstract：:Although antisperm autoantibody responses to obstruction of the male reproductive system have been documented, information on the nature of the cognate sperm autoantigens has been limited. In the present study, the patterns of sperm autoantigens recognized by sera from rats after obstruction of the vas deferens or epi...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/s0165-0378(98)00090-4
更新日期：1999-05-01 00:00:00
abstract：:Members of the galectin family have been shown to exert several roles in the context of reproduction. They contribute to placentation, maternal immune regulation and facilitate angiogenesis encompassing decidualisation and placenta formation during pregnancy. In the context of neo-vascularisation, galectins have been ...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章,评审
doi：10.1016/j.jri.2014.12.001
更新日期：2015-04-01 00:00:00
abstract：:Published data on progeny sex ratio changes resulting from induction or administration of anti-male antibody in parental generation were compared by Fisher's independent test of significance. Sex ratio (males/total) depression is highly significant (P less than 0.001). Our large sample size data confirm this result; s...
journal_title：Journal of reproductive immunology
pub_type： 杂志文章
doi：10.1016/0165-0378(85)90030-0
更新日期：1985-06-01 00:00:00
