Intrauterine environment and fetal allergic sensitization.

Costimulatory molecules in the developing human gastrointestinal tract: A pathway for fetal allergen priming

Differences in amniotic fluid and maternal serum cytokine levels in early midtrimester women without evidence of infection

Amniotic fluid is a dynamic and complex mixture that reflects the physiological status of the developing fetus. In this study, the human amniotic fluid (AF) proteome of a 16-18-week normal pregnancy was profiled and analyzed to investigate the composition and functions of this fluid. Due to the complexity of AF, we utilized three different fractionation strategies to provide greater coverage. Two types of two-dimensional LC/MS/MS as well as an LC-SDS-PAGE-LC-MS/MS platform were used. A total of 16 AF samples between gestational ages of 16 and 18 weeks from women carrying chromosomally normal fetuses were analyzed by one of the three fractionation methods followed by a common reverse phase LC-MS/MS step. Mascot and The Global Proteome Machine engines were used to search the International Protein Index human database for peptide sequence identification. The list of proteins was generated by combining the results of both engines through the PeptideProphet of Scaffold software. All identified proteins were combined to generate the AF proteome comprising 1,026 unique gene matches or 842 non-redundant proteins. This list includes most of the currently used biomarkers for pregnancy-associated pathologic conditions such as preterm delivery, intra-amniotic infection, and chromosomal anomalies of the fetus. The subcellular localization, tissue expression, functions, and networks of the AF proteome were analyzed by various bioinformatic tools. These data will contribute to the better understanding of amniotic fluid function and to the discovery of novel biomarkers for prenatal diagnosis of fetal abnormalities.

Several reports have revealed that human prolactin increases during pregnancy, not only in maternal and fetal serum but also in the amniotic fluid. The source and the role of prolactin in the amniotic fluid however, have not been clear up to now. In their incubation experiment, Riddick et al (29) proved that decidual tissue at term could secret immunoreactive prolactin (IR-PRL). In order to investigate the source of PRL in the amniotic fluid, we extracted IR-PRL from decidual or villous tissue in early normal pregnancies and measured it by a double antibody radioimmunoassay in this experiment. The results were the following: 1) We were able to measure IR-PRL from decidual or villous tissue in early pregnancy, the dilution curve of which paralleled pituitary standard prolactin. The cross reaction of a PRL standard preparation with HCG and HPL was not recognized within 10 micrograms/ml. 2) In human decidual tissue, the IR-PRL concentration began to increase at about the sixth week, arrived at the peak value, 81.06 +/- 2.13 ng/0.1 g dry weight (d.w.) in the eighth week, and did not change significantly after that. In human villous tissue, although the IR-PRL concentration was distinctly lower than it was in the decidual tissue, it increased gradually and reached the level of 37.44 +/- 7.16 ng/0.1g d.w. in the tenth week. 3) The extracted material (IR-PRL) from these two tissues in the 8th week, amniotic fluid at term, and pituitary standard PRL were passed through a Sephadex G-100 column (2 X 93 cm) with phosphate buffer and saline (0.01M, PH 7.4). In the chromatogram of these four test materials, one peak of IR-PRL was observed. The peak of IR-PRL of decidual and villous tissues and amniotic fluid revealed almost the same fraction number but elevated after the pituitary PRL preparation. 4) By gel filtration, the IR-PRL was able to be differentiated from HCG but not from HPL. The peak of HCG appeared earlier than the peak of IR-PRL and HPL. 5) The distribution of IR-PRL between human decidual and villous tissues was significantly different from that of HPL. IR-PRL concentration was higher in the decidual tissue than in the villous tissue, while HPL concentration was higher in the villous tissue than it was in the decidual tissue. From this observation, we could consider that the sources of these two hormones were different. The results of these experiments suggest that one of the sources of PRL in the amniotic fluid was the decidual tissue.

Exposure to ubiquitous allergens early in life, even before birth, may influence the incidence of allergic diseases later in life. During pregnancy, the fetomaternal interface is surrounded by high levels of T-helper (Th)2-like cytokines, possibly favouring the development of Th2-like immune responses in the offspring. The aim of this study was to evaluate the relation between cord blood (CB) IgE antibodies, Th1- and Th2-like cytokines and chemokines, maternal allergy and development of allergic disease during the first 2 yr of life in the offspring. The CB cytokine and chemokine levels from children of 20 allergic and 36 non-allergic women were determined by a multiplexed Luminex assay and ELISA. Total CB and maternal IgE antibody concentrations were quantified using ImmunoCAP technology. The maternal IgE levels during and after pregnancy correlated with CB IgE and Th2-associated macrophage-derived chemokine [MDC (CCL22)] levels. Development of allergic disease and sensitization was associated with increased CB IgE and MDC (CCL22) levels, as well as high ratios of MDC (CCL22) to Th1-associated interferon-gamma inducible protein 10 [IP-10 (CXCL10)] and interferon-gamma inducible T-cell alpha-chemoattractant [I-TAC (CXCL11) (n = 7 allergic vs. n = 25 non-allergic)]. The correlations between maternal IgE and CB IgE and MDC (CCL22) levels possibly indicate that the maternal immunity can affect the Th1/Th2 profile in the neonate. Development of allergic disease is associated with a more marked Th2-like deviation already at birth, shown as increased levels of CB IgE and MDC (CCL22) and higher ratios of MDC (CCL22) to IP-10 (CXCL10) and I-TAC (CXCL11).

Twenty percent of very preterm neonates (23-32 weeks of gestation) are born with bacteremia caused by genital Mycoplasmas

Transfer of maternal IgE can be a common cause of increased IgE levels in cord blood

The significance of allergic family history and cord blood-immunoglobulin E as a predictor of the development of allergic diseases in later life

For newborn children both elevated serum IgE levels in the cord blood and a positive family history of atopic disease have been shown to be risk factors for the manifestation of atopic diseases. In adult patients with atopic dermatitis, in vitro interferon-gamma (IFN-gamma) production is reduced and a negative correlation with serum IgE levels has been shown. We have now raised the question if newborn infants at risk for the development of atopic disease have similar abnormalities of cytokine production at birth. In vitro production of interleukin 2, interleukin 6 and interferon-gamma by peripheral blood mononuclear cells was measured in 53 newborns: 21 had cord blood IgE levels above 0.9 kU/l, 21 had a positive family history, 7 had both elevated IgE and a positive family history; 18 newborns with no identifiable risk for atopic disease served as controls. Umbilical cord blood mononuclear cells were stimulated with PHA or monoclonal antibody OKT3. In vitro production of interleukin 2 and 6 was comparable in all groups. Compared to controls IFN-gamma production of peripheral mononuclear cells (PBMC) from newborns with elevated cord blood IgE was not different, but PMBC from newborns with a familial risk showed a significant decrease in PHA induced IFN-gamma production (p < 0.005, U-test). No correlation between umbilical cord blood IgE and diminished IFN-gamma production was found in newborns with or without a positive family history. We conclude that immunoregulatory abnormalities in newborns of atopic families are detectable already at birth and are unrelated to cord blood IgE.

To what extent the risks of neonatal morbidities are directly related to premature birth or to biological mechanisms of preterm birth remains uncertain. We aimed to examine the effect of exposure to amniotic fluid (AF) infection and elevated cytokine levels on the mortality and pulmonary, intestinal, and neurologic outcomes of preterm infants, and whether these associations persist after adjustment for gestational age at birth. This retrospective cohort study included 152 premature singleton infants who were born at ≤ 32 weeks. AF obtained by amniocentesis was cultured; and interleukin-6 (IL-6) and IL-8 levels in AF were determined. The primary outcome was adverse perinatal outcome defined as the presence of one or more of the followings: stillbirth, neonatal death, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, and periventricular leukomalacia. Logistic regression analysis was adjusted for gestational age at birth and other potential confounders. In bivariate analyses, elevated AF IL-6 and IL-8 levels were significantly associated with adverse perinatal outcome. These results were not changed after adjusting for potential confounders, such as low Apgar scores, mechanical ventilation, and surfactant application. However, the independent effect of elevated cytokine levels in AF disappeared when additionally adjusted for low gestational age at birth; consequently, low gestational age remained strongly associated with the risk of adverse perinatal outcome. In conclusion, elevated levels of pro-inflammatory cytokines in AF are associated with increased risk of adverse perinatal outcomes, but this risk is not independent of low gestational age at birth. Culture-proven AF infection is not associated with this risk.

Depression is a common worldwide burdening mental disease. The amniotic fluid (AF) in both humans and animals has been reported to be associated with reduction of anxiety, pain and with helping the newborns to recognize their mothers. As far as we know, no published work on its possible antidepressant action has been reported before. Therefore, we tested here if AF has an anti-depressant- like activity, and investigated if there is a gender difference in this action. Also, we wanted to find out if this possible action can be modified by a known antidepressant drug. Sixty male and female Wister rats were divided randomly into five groups in each gender, and treated with the following: water (control), human AF, goat AF, venlafaxine and venlafaxine+ human AF. AF and venlafaxine were given orally by gavage at a dose of 0.2ml/ Kgonce a day for five days. Twenty four hours later, locomotor activity test, and the forced swimming test (FST) were measured. Motor activity and immobility time in the FST were both significantly reduced in male and female rats treated with human and caprine AF. Rats treated with human AF showed the least activity. The latter effects were not significantly affected by concomitant treatment with venlafaxine and human AF. The biochemical mechanisms of antidepressant like effect of AF warrant further study.

ObjectivesTo investigate the maternal plasma and amniotic fluid (AF) cytokine concentrations in twin pregnancies complicated by TTTS and the effects of fetoscopic laser ablation (FLA).MethodsA prospective cohort of MC twins...

Objective: Placental trophoblast invasion and amniotic fluid cytokine receptor levels have been reported to vary with fetal gender. We investigated whether fetal gender affects amniotic fluid levels of the inflammatory cytokines interleukin (IL)-6 and IL-10 and the pro-angiogenesis cytokine angiogenin.Methods: Specimens from singleton gestations undergoing mid-trimester amniocentesis for genetic indications were used. Inclusion criteria were (1) outcome information available, (2) no structural or chromosomal anomaly and (3) no conditions associated with preterm delivery. Amniotic fluid IL-6, IL-10 and angiogenin levels were measured by immunoassay. Statistical analysis included the Mann–Whitney U test and Fisher's exact test with p < 0.05 indicating significance.Results: A total of 74 samples were analyzed. Angiogenin levels were significantly lower in amniotic fluid samples from pregnancies with a male than with a female fetus (median (range): 22.2 (5.9–66.4) vs. 32.0 (11.4–159.2) ng/ml, p = 0.007), in contrast to no differences in amniotic fluid IL-6 and IL-10 levels (p = 0.4 and p = 0.1, respectively). In pregnancies with male fetuses delivering preterm (< 37 weeks), angiogenin was also detected at lower levels (p = 0.02). There were no gender differences with respect to race, nulliparity or maternal age.Conclusion: Angiogenin levels, but not IL-6 or IL-10 levels, are significantly lower in second-trimester amniotic fluid of women with male compared with female fetuses, including those women delivering preterm.

Lipopolysaccharide binding protein and soluble CD14 receptor protein in amniotic fluid and cord blood in patients at term

Mycoplasma hominis and Ureaplasma urealyticum in midtrimester amniotic fluid: Association with amniotic fluid cytokine levels and pregnancy outcome