Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia,and their relation with severity of disease

Abstract

Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants.

Methods: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version.

Results: While IFN-gamma and TGF-beta levels of preeclamptic women were significantly higher (p?<?0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p?<?0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age.

Conclusions: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE.     

Serum TNF-α, IL-6, lupus anticoagulant and anticardiolipin antibody in women with and without a past history of recurrent miscarriage

Objective The aim of the this study was to investigate Lupus Anticoagulan (LA), Anticardiolipin Antibody (ACA), Tumor Necrosis Factor- (TNF-) and Interleukin-6 (IL-6) serum levels in 40 pregnant and 20 nonpregnant.Materials and methods The women were divided into three groups. The first group consisted of 20 pregnant women of less than 20 gestational weeks and a past history of habitual abortion . The second group consisted of 20 non pregnant patients with a past history of habitual abortion. The third group consisted of 20 healthy non pregnant women. RESULT: LA was found in only one patient in the Group 2. ACA Ig G positivity were found 1 patient in the Group 1, 3 patients Group 2 and 1 patient in Group 3. Mean ACA IgG was highest in the Group 2. High serum TNF- levels were found in the 12 (60%), 6(30%) and 2 (10%) women in the Groups 1, 2, and 3, respectively. Significant difference were found for TNF- among the groups (P<0.05). The highest level of TNF- was found in the Group 1 and the lowest in the Group 3. There were statistically significant differences for IL-6 among the three groups (P>0.05).Conclusion We propose that cytokines especially TNF- was found to be related to the pregnancy loss.     

Association of Maternal Serum CRP,IL-6, TNF-α, Homocysteine,Folic Acid and Vitamin B12 Levels with the Severity of Preeclampsia and Fetal Birth Weight

Objective: To assess the levels and clinical significance of high sensitive(hs)-CRP (C‐reactive protein), IL-6(interleukin-6), TNF-α(tumor necrosis factor-α), homocysteine, folic acid and vitamin B12 in normotensive healthy pregnant women, mild and severe preeclamptic patients, and to evaluate the correlations between these markers and the severity of preeclampsia and fetal birth weight. Study design: Using a cross-sectional study design, hs-CRP, IL-6, TNF-α, homocysteine and vitamin B12 were measured in the third trimester of pregnancy from normotensive healthy women with uncomplicated pregnancies (n = 62), mild (n = 61) and severe (n = 60) preeclamptic patients. Results: There were statistically significant differences between three groups for hs-CRP (p = 0.012), TNF- α (p = 0.046), IL-6 (p = 0.015), homocysteine (p < 0.001) and fetal birth weight (p < 0.001). Fetal birth weights in mild (2477 ± 746) and severe (2435 ± 768) preeclamptic patients were significantly lower than controls (3485 ± 365) (p < 0.001). No significant difference was found between the three groups for folic acid (p = 0.066) and vitamin B12 (p = 0.286). Bonferroni adjusted multiple comparison test showed that the statistical differences with respect to TNF-α, IL-6 and homocysteine were mainly created by control and severe preeclampsia groups. Hs-CRP levels still remained higher in severe preeclampsia patients than mild preeclampsia and normotensive patients except for overweight patients in the previous two groups after Bonferroni post hoc adjustment test. Conclusion: Elevated maternal serum levels of hs-CRP, TNF- α, IL-6 and homocysteine in preeclamptic women correlate with fetal birth weight in the early third trimester.     

Metformin modulates IL-8, IL-1β, ICAM and IGFBP-1 expression in human endometrial stromal cells

To evaluate the effects of metformin on endometrial stromal cell gene expression and on the decidualization process, endometrial biopsies were collected from five healthy, regularly cycling women. Stromal cell culture was performed and decidualized with oestrogen/progesterone in the presence or absence of metformin and thereafter stimulated with insulin. The effect of metformin on decidualization was analysed by prolactin determination in the cell culture supernatant. Gene expression of insulin-like growth factor binding protein 1 (IGFBP-1), interleukin (IL) 8 and 1β and intercellular adhesion molecule (ICAM) was analysed by real-time PCR. Decidualization was significantly diminished in cells incubated with metformin (P<0.05) accompanied by a significant reduction of prolactin secretion in the supernatant (day 10: 2.2 fold, P<0.05; day 15: 3.1 fold, P<0.05). IGFBP-1 gene expression was reduced after long-term metformin exposure (7.7 fold, P<0.05). The negative effect of insulin on IL-8 (4.8 fold) and IL-1β (9.3 fold) gene expression was similarly found in cells incubated with metformin. As far as is known, this is the first demonstration of a change in endometrial gene and protein expression after in-vitro stimulation with metformin, including a diminished decidualization process and changes in genes relevant to implantation.     

Association of IL-17A and IL-17?F gene polymorphisms with recurrent pregnancy loss in Iranian women

PurposeRecurrent pregnancy loss (RPL) is defined as the occurrence of two or more miscarriages before the 20th week of pregnancy. T helper17 cells are a novel subset of T cells, which secrete IL (Interleukin)-17 and are known to be involved in inflammation, autoimmunity and rejection of non-self tissues. Herein, we studied the association between IL-17A rs2275913 and IL-17F rs763780 gene polymorphisms with RPL in Iranian women.MethodsA case-controlled study was performed on two groups consisting of 85 healthy women with at least one delivery and 85 women with the history of two or more RPLs. The frequency of IL-17A rs2275913 and IL-17 F rs763780 polymorphisms were determined by PCR-RFLP.ResultsIn the RPL group, the genotypes frequencies of rs2275913 polymorphism were GG (8.2 %), AG (30.6 %), and AA (61.2 %) and in the control group, were GG (3.5 %), AG (42.4 %) and AA (54.1 %). Statistical analysis showed no significant difference between the genotypes of AA, AG and GG in the two groups (p = 0.1). The genotypes frequencies of rs763780 polymorphism were TT (43.5 %), TC (49.4 %) and CC (7.1 %) in the RPL group; whereas the frequencies were TT (25.9 %), TC (70.6 %) and CC (3.5 %) in the control group. Statistical analysis revealed a significant difference in the TT, TC, and CC genotypes frequencies between the case and the control groups (p = 0.01).ConclusionsOur findings indicate that IL-17F polymorphism, rs763780, might be associated with a high risk of RPL in Iranian women.     

Sexual and Relationship Intimacy among Women with Provoked Vestibulodynia and Their Partners: Associations with Sexual Satisfaction,Sexual Function,and Pain Self‐Efficacy

IntroductionProvoked vestibulodynia (PVD) is the most frequent subtype of vulvodynia. Women report negative consequences of PVD on their sexual and romantic relationships. Researchers have recently highlighted the importance of examining interpersonal factors such as intimacy, and of including both women and their partners in study designs.AimThe aim of this study was to investigate sexual and relationship intimacy as defined by the Interpersonal Process Model of Intimacy and their associations with sexual satisfaction, sexual function, pain self‐efficacy, and pain intensity among women with PVD and their partners.MethodsNinety‐one heterosexual women (M age = 27.38, SD = 6.04) diagnosed with PVD and their partners (M age = 29.37, SD = 7.79) completed measures of sexual and relationship intimacy, sexual satisfaction, sexual function, pain self‐efficacy, and pain intensity.Main Outcome MeasuresDependent measures were the (i) Global Measure of Sexual Satisfaction Scale; (ii) Female Sexual Function Index; (iii) Painful Intercourse Self‐Efficacy Scale; and (iv) visual analog scale of pain intensity during intercourse.ResultsAfter controlling for women's age, women's greater sexual intimacy (β = 0.49, P < 0.001) was associated with women's greater sexual satisfaction and higher pain self‐efficacy (β = 0.39, P = 0.001), beyond the effects of partners’ sexual intimacy. Also, women's greater sexual intimacy (β = 0.24, P = 0.05) and women's greater relationship intimacy (β = 0.54, P = 0.003) were associated with greater women's sexual function, beyond the effects of partners’ sexual and relationship intimacy.ConclusionsWomen's self‐reported sexual and relationship intimacy in the couple relationship may promote higher sexual satisfaction, sexual function, and pain self‐efficacy, as well as possibly foster greater sexual well‐being among women with PVD. The authors discuss implications for the inclusion of emotional and interpersonal aspects of the couple's dynamic in clinical interventions and future research in PVD. Bois K, Bergeron S, Rosen NO, McDuff P, and Grégoire C. Sexual and relationship intimacy among women with provoked vestibulodynia and their partners: Associations with sexual satisfaction, sexual function, and pain self‐efficacy. J Sex Med 2013;10:2024–2035.     

Different levels of IL-1α, IL-6, TNF-α, NF-κB and PPAR-γ in monocyte cultures exposed by plasma preeclampsia and normotensive pregnancy

ObjectiveTo determine different levels of proinflammatory cytokines IL-1α, IL-6, TNF-α, nuclear NF-κB p50 and PPAR-γ in monocyte cultures exposed to normotensive pregnancy plasma compared with those exposed to preeclamptic plasma.Study designThe study involved primigravidae with preeclampsia (12) and normotensive pregnancy (12) in which their blood plasma was given to monocyte cultures from isolated PBMC of healthy and non-pregnant women. They were divided into 2 groups, the first group was incubated for 24 h and the second one was incubated for 48 h (step 1). The levels of IL-1α, IL-6, TNF-α, and nuclear NF-κB p50 as well as PPAR-γ of both groups were subsequently measured and compared (step 2). Data were analyzed to determine the differences and interaction between both treatment groups using one-way ANOVA.ResultsThere was a significantly different level (p-value <0.05) of IL-1α in monocyte cultures incubated for 24 h compared with those incubated for 48 h, as shown in step 1 of the study. Meanwhile, step 2 of the study found significantly different levels of IL-1α, IL-6, TNF-α, and NF-κB p50 in monocyte cultures exposed to preeclamptic plasma compared with those exposed to normotensive pregnancy, in which the latter showed higher levels. Both groups also showed decreased levels of PPARγ, in which monocyte culture exposed to severe preeclamptic plasma (p value <0.05).ConclusionPreeclamptic plasma significantly increased levels of proinflammatory cytokines IL-1a, IL-6, and TNF-a in monocyte cultures. This condition was consistent with the increasing of NF-κB p50 and decreasing of PPARγ.     

A new,simple, automatic vitrification device: preliminary results with murine and bovine oocytes and embryos

Purpose

This paper reports the use of a novel automatic vitrification device (Sarah, Fertilesafe, Israel) for cryopreservation of oocytes and embryos.

Methods

Mice oocytes (n?=?40) and embryos (8 cells, n?=?35 and blastocysts, n?=?165), bovine embryos (2PN, n?=?35), and MII oocytes (n?=?84) were vitrified using this automated device. A total of 42 (2 cells) mice embryos, 20 (2PN) bovine embryos, and 150 MII bovine oocytes were used as fresh controls and grown to blastocysts. Upon rewarming, all were assessed for viability, cleavage, blastocyst, and hatching rates.

Results

Ninety-five % (38/40) of the mice MII oocytes regained isotonic volumes and all (100%) the surviving were viable. Rewarmed 8-cell mice embryos had 95% (33/35) blastulation rate and 80% (28/35) hatched. Rewarmed mice blastocysts had 97% survival rate (160/165) and 81% (135/165) hatched. Fresh control mice embryos had 100% (42/42) blastulation and 73% (21/42) hatching rates. Bovine embryos’ survival was 100% with 54% (19/35) cleavage and 9% (3/35) blastulation rate. Fresh control bovine embryos had 65% (13/20) cleavage and 20% (4/20) blastulation rate. Vitrified bovine oocytes had 100% survival (84/84), 73% (61/84) cleavage, and 7% (6/84) blastocysts’ rates; fresh control had 83% (125/150) cleavage and 11% (17/150) blastocysts’ rates.

Conclusion

This novel automatic vitrification device is capable to produce high survival rates of oocytes and embryos. We anticipate that as the demand for vitrification of gametes, embryos, and reproductive tissues increases worldwide, the availability of an automated vitrification device will become indispensable for standardization, simplification, and reproducibility of the entire process.

     

Expression of lipoxin A4, TNFα and IL-1β in maternal peripheral blood,umbilical cord blood and placenta,and their significance in pre-eclampsia

Objective: The purpose of this study was to investigate the expression of lipoxin A₄, TNFα and IL-1β in maternal peripheral blood, umbilical cord blood and placenta, and to assess their significance in pre-eclampsia. Methods: Ninty pregnant women were divided into three groups: a mild PE group (n?=?30), a severe PE group (n?=?30) and a control group (n?=?30). We measured serum levels of lipoxin A₄, TNFα and IL-1β using ELISA. Expression levels of lipoxin receptor (FPR2/ALX) mRNA were compared using quantitative RT-PCR. Results: Mean circulating levels of lipoxin A₄, TNFα and IL-1β in the PE groups were significantly increased compared with matched women in the control group. The ratios of lipoxin A₄/TNFα and of lipoxin A₄/IL-1β in the PE groups were significantly decreased compared with matched women in the control group. No lipoxin A₄ was detected in umbilical cord blood. There was a significant increase in FPR2/ALX mRNA expression in placenta obtained from the PE groups. Conclusions: The level of lipoxin A₄ in maternal peripheral blood may correlate with the expression of FPR2/ALX in placenta. Lipoxin A₄ increased to a lesser degree than either TNFα or IL-1β with progression of PE. This may be one of the reasons why oxidative stress and endothelial dysfunction in severe preeclamptic patients are much more serious that in cases of less severe preeclampsia. Moreover, lipoxin A₄ does not have any effect on the fetus through the placenta. We conclude that supplementing with lipoxin A₄ to ensure adequate levels may be a novel method for the treatment of pre-eclampsia without any effects on the fetus.     

Gamete donors’ reasons for,and expectations and experiences of,registration with a voluntary donor linking register

This paper reports on a study of the views and experiences of 21 sperm donors and five egg donors registered with UK DonorLink (UKDL), a voluntary DNA-based contact register established to facilitate contact between adults who wish to identify and locate others to whom they are genetically related following donor conception. Specifically, the paper examines donors’ reasons for searching for, or making information about themselves available to donor-conceived offspring. Their expectations of registration with UKDL, experiences of being registered and finally, the experiences of those who had contacted donor-conceived offspring and other genetic relatives are investigated. While most respondents reported largely positive experiences of registration, the study found significant issues relating to concerns about donation, DNA testing, possible linking with offspring and expectations of any relationship that might be established with offspring that have implications for support, mediation and counselling. Research that puts the experiences, perceptions and interests of gamete donors as the central focus of study is a relatively recent phenomenon. This study contributes to this debate and highlights directions for future research in this area.     

Group B Streptococcus colonization and higher maternal IL-1β concentrations are associated with early term births

Association between maternal Group B Streptococcus (GBS) colonization diagnosed between 35 and 37 weeks of gestation and early term birth (between 37 and 39 weeks) and maternal-fetal inflammatory response associated with this condition were tested. In this cohort study of women delivering at term at Centennial Women’s Hospital in Nashville, TN, GBS status and other clinical and demographic data were obtained from medical records. Exposed women were those testing positive for GBS (GBS positive [n?=?490]) and the unexposed tested negative for GBS (GBS negative [n?=?1,127]). To determine the inflammatory response associated with GBS, a cross sectional study, maternal and fetal plasma biomarkers (IL-1β, IL-2, IL-6, IL-8, and TNF-α) were measured in the same cohort. T-tests and logistic regression determined association between GBS status, biomarker concentrations and early term birth. Gestational age was reduced to 271.1 (95% CI 270.4, 271.1) for cases compared to 274.7 (95% CI 274.4, 275.1) days for controls (p < 0.0001). The odds of early term birth was increased by threefold in cases (OR 3.28; 95% CI 2.60–4.15; p < 0.0001). The mean birth weight in cases (3285.3?g) (95% CI 3242.6, 3327.9) was lower than the controls, 3373.8?g (95% CI 3348.9, 3398.7) (p = 0.0004). Maternal IL-1β was greater in cases (22.8?ng/ml; range 5.2–157.7?ng/ml) compared to controls (5.7; range 2.4–69.5?ng/ml; p < 0.0001). IL-1β was higher in fetal plasma in cases vs. controls (20.33 vs. 8.18?ng/ml; p = 0.01). A 10?ng/ml increase in maternal IL-1β was associated with increased risk for GBS infection (OR: 1.628, CI: 1.163–2.278; p = 0.0045). GBS colonization shortened gestational age at term and IL-1β concentration in maternal plasma is an indicator of GBS status.     

足月妊娠产妇羊水中IL-6,IFN-γ,IL-8,GM-CSF的浓度

细胞因子有助于成功地维持妊娠,并与启动分娩有关。IL-6能刺激羊膜及蜕膜产生PGE_2,与正常分娩的生理学有关;IL-8与子宫颈的成熟过程有关,有报道证实在分娩过程中子宫下段IL-8产生增多。在人妊娠过程中,胎盘合体滋养层产生IFN-γ,蜕膜及滋养层产生GM-CSF。这些细胞因子的部分功能与胎盘的生长及分化有关,但它们对分娩机制的作用尚不清楚。为确定可能与足月妊娠分娩机制有关的细胞因子,检测母体外周血,子宫静脉血,脐动脉血,羊水中IL-6,IFN-γ,IL-8及GM-CSF的浓度。方法:实验组10例标本为顺产妇(6例羊膜未破,4例羊膜破裂<6h);对照组标本为剖宫产产妇。分别取外周血,子宫静脉血,脐动脉血及羊水,应用ELISA     

A neonate with the Pelger-Hu?t anomaly, cleft lip and palate, and agenesis of the corpus callosum, with a chromosomal microdeletion involving 1q41 to 1q42.12

We observed a neonate with cleft lip and palate, 13 sets of ribs, agenesis of the corpus callosum, slightly small penis, hypoglycemia, and what initially appeared to be a marked leukocyte 'left shift' on complete blood count, but which was actually a Pelger-Hu?t anomaly. A chromosomal microdeletion was identified at1q41-42.12.     

IL-1β and IL-23 in amniotic fluids of ultrasound-detected aortic intima/media thickness and growth retardation

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.