42 research outputs found
RECURRENT PREGNANCY LOSS IS ASSSOCIATED TO LEAKY GUT: A NOVEL PATHOGENIC MODEL OF ENDOMETRIUM INFLAMMATION ?
Background: Recurrent pregnancy loss (RPL) occurs in 3\u20135% in about 30% of cases no cause can be found. Women
with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women,
higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was
to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic
circulation of pro-inflammatory molecules able to induce endometrial inflammation.
Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss
Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent
51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled
women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering
STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20
healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were
investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1\u3b2 and IL-18 by ELISA, respectively.
Results: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS
(P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial
expression of Nalp-3, caspase-1 and IL-1\u3b2 was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001,
respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association
between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in
RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be
statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women.
Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers,
potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis.
Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and
pregnancy outcome
Correction to: Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation?
Background: Recurrent pregnancy loss (RPL) occurs in 3â5% in about 30% of cases no cause can be found. Women
with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women,
higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was
to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic
circulation of pro-inflammatory molecules able to induce endometrial inflammation.
Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss
Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent
51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled
women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering
STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20
healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were
investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1ÎČ and IL-18 by ELISA, respectively.
Results: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS
(P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial
expression of Nalp-3, caspase-1 and IL-1ÎČ was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001,
respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association
between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in
RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be
statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women.
Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers,
potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis.
Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and
pregnancy outcome
α-Lipoic Acid and its Role on Female Reproduction
alpha-lipoic Acid (ALA), also known as thioctic acid, is a biological thiol present in all types of prokaryotic and eukaryotic cells. It has been shown that ALA or its reduced form, DHLA, has several positive effects on human health, acting as a biological antioxidant, metal chelator and detoxifying agent. It is able to reduce the oxidation of several antioxidant agents like glutathione, vitamins C and E, and modulate insulin and NF-kB signaling pathways. ALA's pharmacological effects are not only related to its antioxidant properties but it shows an anti-inflammatory action. In particular, ALA is able to reduce inflammasome activity, the pro-inflammatory cytokine levels, such as TNF-alpha, IL-1 beta, IL-6, IL-18 and IL-17, interferon (INF)-gamma as well as the production of Vascular and Intercellular cell adhesion protein (VCAM-1 and ICAM-1). In recent papers, ALA has been indicated as a possible therapeutic approach to several endocrine or inflammatory disorders affecting female reproduction. Aim of the current review was to assess whether ALA has an evidence-based beneficial role on gynecological and obstetrical diseases such as polycystic ovary syndrome (PCOS), endometriosis, and miscarriage
Resistin modulates glucose uptake and glucose transporter-1 (GLUT-1) expression in trophoblast cells
Abstract
The adipocytokine resistin impairs glucose tolerance and insulin sensitivity. Here, we examine the effect of resistin on glucose uptake in human trophoblast cells and we demonstrate that transplacental glucose transport is mediated by glucose transporter (GLUT)-1. Furthermore, we evaluate the type of signal transduction induced by resistin in GLUT-1 regulation. BeWo choriocarcinoma cells and primary cytotrophoblast cells were cultured with increasing resistin concentrations for 24 hrs. The main outcome measures include glucose transport assay using [3H]-2-deoxy glucose, GLUT-1 protein expression by Western blot analysis and GLUT-1 mRNA detection by quantitative real-time RT-PCR. Quantitative determination of phospho(p)-ERK1/2 in cell lysates was performed by an Enzyme Immunometric Assay and Western blot analysis. Our data demonstrate a direct effect of resistin on normal cytotrophoblastic and on BeWo cells: resistin modulates glucose uptake, GLUT-1 messenger ribonucleic acid (mRNA) and protein expression in placental cells. We suggest that ERK1/2 phosphorylation is involved in the GLUT-1 regulation induced by resistin. In conclusion, resistin causes activation of both the ERK1 and 2 pathway in trophoblast cells. ERK1 and 2 activation stimulated GLUT-1 synthesis and resulted in increase of placental glucose uptake.
High resistin levels (50â100 ng/ml) seem able to affect glucose-uptake, presumably by decreasing the cell surface glucose transporter
Correction to: Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation?
Following publication of the original article [1], the authors reported updated affiliations for five of the authors. The updated affiliations are shown below and reflected in the affiliation list of this Correction
Decreased expression of heparin-binding epidermal growth factor-like growth factor as a newly identified pathogenic mechanism of antiphospholipid-mediated defective placentation
Objective. Heparin-binding epidermal growth
factor\u2013like growth factor (HB-EGF) plays a role in
blastocyst implantation and is down-regulated in preeclampsia
and in hypertensive pregnancy disorders
associated with defective extravillous trophoblast invasion.
Defective placentation and severe preeclampsia
are also features of the antiphospholipid syndrome
(APS). The purpose of this study was to investigate
whether abnormal HB-EGF expression plays a pathogenic
role in antiphospholipid antibody (aPL)\u2013mediated
defective placentation.
Methods. HB-EGF expression in placental tissue
was evaluated by Western blotting and messenger RNA
analysis in normal and APS placentae. Polyclonal IgG
fractions or monoclonal 2-glycoprotein I\u2013dependent
aPL and their respective controls were investigated for
the following 4 features: their binding to human trophoblast
monolayers, as determined by cell enzyme-linked
immunosorbent assay (ELISA); their effect on HB-EGF
expression by Western blotting in trophoblast cell extracts
as well as by ELISA as a protein secreted in the
culture supernatants; their inhibitory effect on in vitro
trophoblast invasiveness, as evaluated by Matrigel assay;
and their inhibitory effect on matrix metalloproteinase
(MMP) levels, as measured by gelatin zymography.
Experiments were also performed in the presence
of serial concentrations of heparin or recombinant
HB-EGF.
Results. Placental APS tissue displayed reduced
expression of HB-EGF. Polyclonal and monoclonal aPL
bound to trophoblast monolayers and significantly reduced
the in vitro synthesis and secretion of HB-EGF.
Heparin inhibited aPL binding and restored HB-EGF
expression in a dose-dependent manner. Addition of
recombinant HB-EGF reduced the in vitro aPL-induced
inhibition of Matrigel invasiveness as well as MMP-2
levels.
Conclusion. These preliminary findings suggest
that the reduction of aPL-mediated HB-EGF represents
an additional mechanism that is responsible for the
defective placentation associated with APS and that
heparin protects from aPL-induced damage by inhibiting
antibody binding