Inadvertent antibiotic exposure during pregnancy may increase the risk for neural tube defects in offspring.

BACKGROUND: As emerging environmental contaminants, antibiotics pose potential threats to human health, in particular to pregnant women and infants. However, the potential harm of inadvertent antibiotic exposure (IAE) is often disregarded in light of the focus on intentional antibiotic use during pregnancy. Currently, little is known about the effects of IAE during pregnancy on fetal neural tube development. METHODS: In this case-control study, we used questionnaire data from 855 subjects to investigate the effects of intentional antibiotic use in early pregnancy on neural tube defects (NTDs). Then we tested for placental antibiotics in mothers who had not intentionally used antibiotics, and the compounds were detected in 379 subjects; these were considered IAE cases. We assessed the association between IAE during pregnancy and fetal NTDs using both multivariable logistic and multi-pollutant exposure models. We also analyzed the correlation between maternal dietary habits and placental antibiotics to explore possible sources of IAE. RESULTS: Only 50 of 855 participants (5.8%) intentionally used antibiotics and such use showed no significant association with NTD risk (odds ratio [OR] = 1.92, confidence interval [95%CI] = [0.66, 5.59]). However, 14 of 15 placental antibiotics were detected in 378 of 379 subjects (99.7%) and multivariable logistic analysis indicated that high levels of placental macrolides were significantly associated with increased NTD risk (4.42 [2.01-10.45]). Multi-pollutant exposure analysis suggested an increase in NTD risk with an increase in exposure to a mixture of placental antibiotics, among which macrolides were the most important contributor. In addition, the level of placental macrolides was positively correlated with the intake frequency of milk. Finally, mothers who drank river, well, or pond water had higher levels of placental macrolides than those who drank only tap water. CONCLUSIONS: Intentional antibiotic use during early pregnancy may not be associated with NTDs, while IAE during pregnancy is associated with higher NTD risk in offspring. Macrolides are crucial risk factors. Milk, and river, well, or pond water may be important sources of IAE.

Expression and significance of CEMIP and CYP11B2 in serum in women with foetal growth restriction.

BACKGROUND: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR. METHODS: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed. RESULTS: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P < 0.001). CEMIP (95%CI: 0.802-0.921, P < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P < 0.001) were independent predictors of FGR, and CEMIP (r = -0.578, P = 0.001) and CYP11B2 (r = -0.602, P < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR. CONCLUSION: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.

Foetal growth restriction is the inability of the foetus to reach its growth potential in the uterus due to various factors. This study aimed to investigate the expression and significance of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction. In our study, we found that the expression of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction were decreased. Cell migration-including protein and aldosterone synthase expression was negatively correlated with soluble fms like tyrosine kinase-1/placental growth factor ratio. In addition, the study also found that cell migration-including protein and aldosterone synthase expression in serum had good diagnostic value for foetal growth restriction.

Methylation Status of IGF-Axis Genes in the Placenta of South Indian Neonates with Appropriate and Small for Gestational Age.

OBJECTIVE: Altered methylation patterns of insulin-like growth factor (IGF)-axis genes in small for gestational age (SGA) have been reported in different populations. In the present study, we analyzed the methylation status of IGF-axis genes in the placenta of appropriate for gestational age (AGA) and SGA neonates of South Indian women. METHODS: Placental samples were collected from AGA (n = 40) and SAG (n = 40) neonates. The methylation of IGF-axis genes promoter was analyzed using MS-PCR. RESULTS: IGF2, H19, IGF1, and IGFR1 genes promoter methylation was 2.5, 1.5, 5, and 7.5% lower in SGA compared to AGA, respectively. Co-methylation of IGF-axis genes promoter was 40% and 20% in AGA and SGA, respectively. IGF-axis gene promoter methylation significantly (p < 0.05) influenced the levels of IGFBP3 protein, birth weight, mitotic index, gestational weeks, and IGFR1 and IGFR2 gene expression. CONCLUSION: IGF-axis genes methylation was lower in SGA than in AGA, and the methylation significantly influenced the IGF-axis components.

Prenatal exposure to per- and polyfluoroalkyl substances and pregnancy outcome in Austria.

Per- and polyfluoroalkyl substances (PFAS) are a large group of persistent industrial chemicals that can harm reproductive health. PFAS levels were analysed to determine the current sources of exposure and possible associations between prenatal PFAS exposure and adverse pregnancy outcome. Samples from 136 mother-newborn pairs recruited between 2017 and 2019 were analysed for the presence of 31 target PFAS in maternal serum, umbilical cord serum, and placental tissue by high-performance liquid chromatography coupled to a tandem mass spectrometer. Questionnaires and medical records were used to survey sources of exposure and pregnancy outcome, including small for gestational age (SGA), fetal growth restriction (FGR), preeclampsia (PE), preterm birth, large for gestational age (LGA) and gestational diabetes mellitus (GDM). Data were analysed for individual PFAS and sum4PFAS (sum of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) serum levels) in logistic regression analyses and categorical regression analyses. Compared to data from a previous Viennese study in 2010-12, sum4PFAS levels were generally lower. Sum4PFAS serum levels of three women (2.2%) exceeded 6.9 µg/L, a level that corresponds to the recently established tolerable weekly intake (TWI) of EFSA for nursing mothers aged 35 years; in the 2010/2012 study it was 13.6%. The large contribution of unidentified extractable organofluorine (EOF) fractions to total PFAS exposure is a concern. Study site, mean maternal corpuscular hemoglobin (MCH), use of facial lotion, and owning upholstered furniture were significantly influencing maternal exposure. While no effect of sum4PFAS on pregnancy outcome could be detected, we found highest placental PFDA levels in SGA births. PFHxS levels in umbilical cord and placenta were highest in preterm births. Further studies are needed to elucidate the relationship of prenatal PFAS exposure and pregnancy outcome, in particular to confirm whether and how placental PFDA levels may contribute to an increased risk for SGA.

Expression pattern and clinical significance of microRNA-let-7a and IFN-gamma in placental tissue of patients with preeclampsia with severe features.

OBJECTIVES: Preeclampsia with severe features (PECsf) is a common disease in pregnant women. let-7a and IFN-gamma (interferon-gamma) are involved in diagnosis and prognosis of preeclampsia. This study explored effects of let-7a and IFN-gamma on PECsf patients. METHODS: The placental tissue of 21 PECsf, 19 preeclampsia without severe features (PEC), and 20 normal pregnant women were collected, and clinical data were recorded. let-7a and IFN-gamma expressions in placental tissue were detected. The correlation between let-7a/IFN-gamma expression and clinical indexes was analyzed. According to let-7a and IFN-gamma expressions, PECsf patients were assigned into Hlet-7a group (let-7a high expression group), Llet-7a group (let-7a low expression group), HIFN-gamma group (IFN-gamma high expression group) and LIFN-gamma group (IFN-gamma low expression group). The incidence of adverse prognosis was compared. RESULTS: let-7a and IFN-gamma were highly expressed in placental tissue of preeclampsia patients, with significant differences between PEC and PECsf. The high expressions of let-7a and IFN-gamma were positively correlated with mean arterial pressure, lactate dehydrogenase, and 24 h urinary protein in placental tissues of PECsf patients. High let-7a and IFN-gamma expressions were correlated with adverse outcomes of PECsf. CONCLUSIONS: High let-7a and IFN-gamma expressions were correlated with clinical features, and could be used as biomarkers for treatment and poor prognosis of PECsf.

Oxidative Stress and DNA Damage Effect of Dioscorea hispida Dennst. on Placental Tissues of Rats.

Dioscorea hispida Dennst. locally known as "ubi gadung" has been used as a traditional remedy and source of carbohydrate among Malaysians. To assess the effect of Dioscorea hispida aqueous extract (DHAE) on the production of reactive oxygen species (ROS) and their effects on DNA damage in Sprague Dawley rat's placental tissues, pregnant rats were randomly divided into four groups. The animals were orally treated with distilled water (negative control) and three different concentrations of DHAE (250, 500 and 1000 mg/kg body weight (BW)) from gestation day 6 until 20. The oxidative stress in placental tissues was evaluated at day 21 by measuring the level of ROS, superoxide dismutase (SOD) and lipid peroxidation biomarker, malondialdehyde (MDA) while comet assay was used for DNA damage. There was no significant production of ROS and SOD activities in all groups. Significant changes were observed in the MDA level at 1000 mg/kg BW DHAE. Comet assay revealed a significant increase (p < 0.05) of DNA damage on animals treated with 250 and 500 mg/kg BW DHAE but not at the highest concentration. It was postulated that the placental cells could have undergone necrosis which destroys all components including DNA. This occurrence simultaneously reduces the levels of DNA damage which can be represented by lower level of tail moments. This finding correlates with our histopathological examination where necrotic cells of spongiotrophoblast were observed in the basal zone of placental tissue. The high amount of hydrogen cyanide and other compounds in 1000 mg/kg BW DHAE could elevate the lipid peroxidation and directly induce cell necrosis which requires further investigation.

[Uterine vascular abnormalities]. / Sosudistye anomalii matki.

Congenital and acquired vascular abnormalities of the uterus are quite rarely, but they are given much attention in the scientific literature due to the risk of life-threatening bleeding. In the uterus, as in any other organs, malformations can involve vessels of any caliber and type. The review summarizes the materials by clinical characteristics, pathogenesis, diagnostic methods, morphological features and management tactics of patients with uterine arteriovenous malformations. Enhanced myometrial vascularity in the puerperium due to retained placental tissue are also considered. The issues of terminology and differential diagnosis of these conditions are discussed, which is important in connection with significantly different approaches to treatment.

Extractable Organofluorine Analysis in Pooled Human Serum and Placental Tissue Samples from an Austrian Subpopulation-A Mass Balance Analysis Approach.

Embryos and fetuses are of major concern due to their high vulnerability. Previous studies demonstrated that human exposure to per- and polyfluoroalkyl substances (PFAS) may be underestimated because only a limited number of known PFAS can be measured. This investigation studied the total PFAS exposure by measuring the extractable organofluorine (EOF) in pooled maternal serum, placental tissue, and cord serum samples (total number of pooled samples: n = 45). The EOF was analyzed using combustion ion chromatography, and the concentrations of known PFAS were determined using ultraperformance liquid chromatography coupled with a tandem mass spectrometer. Using a mass balance analysis approach, the amount of unknown PFAS was estimated between the levels of known PFAS and EOF. The EOF levels ranged from 2.85 to 7.17 ng F/mL (21 PFAS were quantified) in the maternal serum, from 1.02 to 1.85 ng F/g (23 PFAS were quantified) in the placental tissue, and from 1.2 to 2.10 ng F/mL (18 PFAS were quantified) in the cord serum. An average of 24, 51, and 9% of EOF is unidentified in the maternal serum, placental tissue, and cord serum, respectively. The results show that the levels of unidentified EOF are higher in the placental tissue, suggesting accumulation or potential transformation of precursors in the placenta.

Comparison of extraction methods for per- and polyfluoroalkyl substances (PFAS) in human serum and placenta samples-insights into extractable organic fluorine (EOF).

Since the detection of per- and polyfluoroalkyl substances (PFAS) in humans and different environmental media in the last two decades, this substance group has attracted a lot of attention as well as increasing concerns. The fluorine mass balance approach, by comparing the levels of targeted PFAS after conversion to fluorine equivalents with those of extractable organic fluorine (EOF), showed the presence of unidentified organofluorine in different environmental samples. Out of the thousands of PFAS in existence, only a very small fraction is included in routine analysis. In recent years, liquid chromatography coupled with tandem-mass spectrometry (LC-MS/MS) has demonstrated the ability to analytically cover a wide spectrum of PFAS. In contrast, conventional extraction methods developed 10 to 15 years ago were only evaluated for a limited number of PFAS. The aim of the present study was to evaluate the advantages and disadvantages of three different extraction methods, adapted from the literatures without further optimization (ion-pair liquid-liquid extraction, solid-phase extraction (SPE), using hydrophilic-lipophilic (HLB) or weak anion exchange (WAX) sorbents), for human biomonitoring of 61 PFAS in serum and placental tissue samples. In addition, levels of EOF were compared among these extraction methods via spiked samples. Results showed that performance, in terms of recovery, differed between the extraction methods for different PFAS; different extraction methods resulted in different EOF concentrations indicating that the choice of extraction method is important for target PFAS and EOF analysis. Results of maternal serum samples, analyzed in two different laboratories using two different extraction methods, showed an accordance of 107.6% (± 21.3); the detected perfluoroalkyl acids (PFAAs) in maternal and cord serum samples were in the range of 0.076 to 2.9 ng/mL.Graphical abstract.

Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines.

The application of anticancer drugs during pregnancy is associated with placenta-related adverse pregnancy outcomes. Therefore, it is important to study placental toxicity of anticancer drugs. The aim of this study was to compare effects on viability and steroidogenesis in placental tissue explants and trophoblast cell lines. Third trimester placental tissue explants were exposed for 72 h (culture day 4-7) to a concentration range of doxorubicin, paclitaxel, cisplatin, carboplatin, crizotinib, gefitinib, imatinib, or sunitinib. JEG-3, undifferentiated BeWo, and syncytialised BeWo cells were exposed for 48 h to the same drugs and concentrations. After exposure, tissue and cell viability were assessed and progesterone and estrone levels were quantified in culture medium. Apart from paclitaxel, all compounds affected both cell and tissue viability at clinically relevant concentrations. Paclitaxel affected explant viability moderately, while it reduced cell viability by 50% or more in all cell lines, at 3-10 nM. Doxorubicin (1 µM) reduced viability in explants to 83 ± 7% of control values, whereas it fully inhibited viability in all cell types. Interference with steroid release in explants was difficult to study due to large variability in measurements, but syncytialised BeWo cells proved suitable for this purpose. We found that 1 µM sunitinib reduced progesterone release to 76 ± 6% of control values, without affecting cell viability. While we observed differences between the models for paclitaxel and doxorubicin, most anticancer drugs affected viability significantly in both placental explants and trophoblast cell lines. Taken together, the placenta should be recognized as a potential target organ for toxicity of anticancer drugs.

Pesticides exposure through environment and risk of pre-term birth: a study from Agra city.

Pre-term birth is an increasingly prevalent complex condition with multiple risk factors including environmental pollutants. Evidences linking organochlorine pesticides with adverse pregnancy outcomes are inconsistent for link between organochlorine pesticides and adverse pregnancy outcomes. We performed a case-control study of 50 cases of full-term births and 40 cases of pre-term births in this study. Placental organochlorine pesticides like metabolites of dichlorodiphenyltrichloroethane that is, (p,p-DDE, p,p-DDT and o,p-DDD) and isomers of hexachlorocyclohexane (α, ß, γ and δ HCH) were analyzed by gas chromatography. Although the mean levels of pesticide were found higher in the placenta of the women with pre-term delivery cases placentas, but only α-HCH, total-HCH, p,p-DDE and total-DDT were found statistically significant. It was observed that pesticide exposed women were approximately 1.7 times more likely to deliver pre-term baby as compare to pregnant women that were not exposed to any pesticides. We also observed that increasing maternal age reduced the risk of having pre-term birth (OR = 0.99). Among all pesticides, α-HCH was found to be strongest isomer to induce premature baby birth (p < 0.001). This study found that pregnant women's age and chronic disease, baby's weight at the time of birth and α-HCH were important risk factors for pre-term births.

Accuracy of One Step malaria rapid diagnostic test (RDT) in detecting Plasmodium falciparum placental malaria infection in women living in Yaoundé, Cameroon.

BACKGROUND: Plasmodium falciparum infected erythrocytes sequestering in placental tissue release Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein-II (HRP-II). These proteins can be detected in peripheral blood using monoclonal antibody-based rapid diagnostic tests (RDTs). Nevertheless, studies to evaluate the reliability of RDTs in detecting placental malaria compared with microscopy of placental tissue impression smear (PTIS) as the gold standard are scarce. METHODS: Between August 2013 and January 2015, Giemsa-stained blood smears for peripheral blood smear (Pbs), placental intervillous space (IVS) blood smear and placental tissue impression smear (PTIS)] were prepared from HIV-negative women during delivery at the Marie Reine Medical Health Centre in Yaoundé, Cameroon. RDTs with monoclonal antibodies specific to HRP-II (P.f) or pLDH (Pan) antigens were used to screen maternal peripheral blood samples. RESULTS: The prevalence of malaria was 16%, 7.5%, 11.5%, 8% and 13% for One Step malaria HRP-II and pLDH RDTs, peripheral blood smear, IVS blood and placental tissue impression smears, respectively. The proportion of women positive by One Step malaria pLDH RDT and Pbs increased with parasite density in PTIS, while One Step malaria HRP-II RDT detected high proportion of infected women even with low parasite density. Although the prevalence of malaria infection by both microscopy and RDTs decreased significantly with mother age (0.0008 ≤ p ≤ 0.025), parity seemed to have very little influence. The sensitivity of One Step malaria HRP-II and pLDH RDTs were 96.15% and 61.53%, respectively, compared to 80.76% for Pbs (p = 0.014 and 0.0029, respectively). The specificity of these RDTs was 96.49% and 100%, respectively, compared to 100% for Pbs (p ≥ 0.12). In addition, the positive predictive values were 80.64% and 100% for HRP-II and pLDH-based RDTs, respectively, compared to 100% for Pbs (p < 0.0001 and 1, respectively), while the negative predictive values were 99.40% and 94.48%, respectively, compared to 97.16% for Pbs (p ≥ 0.49). The combination of One Step malaria HRP-II RDT and Pbs showed the similar performance as that observed with One Step malaria HRP-II RDT only. CONCLUSION: These results depict One Step malaria HRP-II RDT to be better in detecting placental P. falciparum infection in pregnant women compared to Giemsa-stained peripheral thick blood smear. This is important for better case management since microscopic examination of PTIS cannot be employed during pregnancy.

Placental tissue metabolome analysis by GC-MS: Oven-drying is a viable sample preparation method.

Analysis of the human placenta metabolome has great potential to advance the understanding of complicated pregnancies and deleterious fetal outcomes in remote populations, but samples preparation can present unique challenges. Herein, we introduce oven-drying as a simple and widely available method of sample preparation that will facilitate investigations of the placental metabolome from remote and under-studied populations. Placentae from complicated and uncomplicated pregnancies were prepared in three ways (oven-dried at 60 °C, fresh, lyophilized) for metabolome analysis via gas chromatography-mass spectrometry (GC-MS). Multiple computer models (e.g. PLS-DA, ANN) were employed to classify and determine if there was a difference in placentae metabolome and a group of metabolites with high variable importance in projection scores across the three preparations and by complicated vs. control groups. The analyses used herein were shown to be thorough and sensitive. Indeed, significant differences were detected in metabolomes of complicated vs. uncomplicated pregnancies; however, there were no statistical differences in the metabolome of placentae prepared by oven-drying vs. lyophilization vs. fresh placentae. Oven-drying is a viable sample preparation method for placentae intended for use in metabolite analysis via GC-MS. These results open many possibilities for researching metabolome patterns associated with fetal outcomes in remote and resource-poor communities worldwide.

Placental mitochondrial DNA and CYP1A1 gene methylation as molecular signatures for tobacco smoke exposure in pregnant women and the relevance for birth weight.

BACKGROUND: Maternal smoking during pregnancy results in an increased risk of low birth weight through perturbations in the utero-placental exchange. Epigenetics and mitochondrial function in fetal tissues might be molecular signatures responsive to in utero tobacco smoke exposure. METHODS: In the framework of the ENVIRONAGE birth cohort, we investigated the effect of self-reported tobacco smoke exposure during pregnancy on birth weight and the relation with placental tissue markers such as, (1) relative mitochondrial DNA (mtDNA) content as determined by real-time quantitative PCR, (2) DNA methylation of specific loci of mtDNA (D-loop and MT-RNR1), and (3) DNA methylation of the biotransformation gene CYP1A1 (the last two determined by bisulfite-pyrosequencing). The total pregnant mother sample included 255 non-smokers, 65 former-smokers who had quit smoking before pregnancy, and 62 smokers who continued smoking during pregnancy. RESULTS: Smokers delivered newborns with a birth weight on average 208 g lower [95% confidence interval (CI) -318 to -99, p = 0.0002] than mothers who did not smoke during pregnancy. In the smoker group, the relative mtDNA content was lower (-21.6%, 95% CI -35.4 to -4.9%, p = 0.01) than in the non-smoker group; whereas, absolute mtDNA methylation levels of MT-RNR1 were higher (+0.62%, 95% CI 0.21 to 1.02%, p = 0.003). Lower CpG-specific methylation of CYP1A1 in placental tissue (-4.57%, 95% CI -7.15 to -1.98%, p < 0.0001) were observed in smokers compared with non-smokers. Nevertheless, no mediation of CYP1A1 methylation nor any other investigated molecular signature was observed for the association between tobacco smoke exposure and birth weight. CONCLUSIONS: mtDNA content, methylation of specific loci of mtDNA, and CYP1A1 methylation in placental tissue may serve as molecular signatures for the association between gestational tobacco smoke exposure and low birth weight.

[Convention Ultrasound and Contrast-enhanced Ultrasound Imaging in the Diagnosis of Placenta Implantation].

OBJECTIVES: To determine the value of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in the diagnosis of placenta residue with implantation. METHODS: We retrospectively analyzed 112 cases of placenta remnants from Apr. 2013 to Mar. 2016, all of which were confirmed by pathological results. The cases were divided into implanted (n =74) and non-implanted (n =38) groups. We compared the characteristics of US and CEUS imaging between the two groups. Multi-variate logistic regression models were established to assess the accuracy of ultrasound imaging in predicting implantation, including the area under the curve (AUC ) of receiver operating characteristic (ROC) curves. RESULTS: US detected intrauterine lesions, with significant differences between the two groups in the clearness of boundaries of lesions (P <0.05) . Differences between the two groups were also found in CEUS in enhanced phase, enhanced intensity, existence of clear and regular boundaries, and reduced muscle thickness in the lesion area (P <0.05). CEUS (91.1%) and US+CEUS (92.0%) had a higher prediction accuracy for placenta implantation compared with US (87.5%) (P <0.05). The AUC of CEUS (0.922) and US+CEUS (0.952) were also significantly higher than that of US (0.887) (P <0.05). No significant differences were observed between CEUS and US+CEUS. CONCLUSION: The value of CEUS for predicting placenta implantation is higher than US.

Biochemical Markers of Oxidative Stress in Saudi Women with Recurrent Miscarriage.

This study was undertaken to investigate the antioxidant/oxidant status in recurrent miscarriage patients. Antioxidants including glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), reduced glutathione (GSH) and selenium (Se), as well as the oxidants hydrogen peroxide (H2O2), oxidised glutathione (GSSG) and lipid peroxidation were assayed in plasma, whole blood and placental tissue of non-pregnant women (NP), healthy pregnant women (HP), and recurrent miscarriage (RM) patients. Results indicated that all antioxidant activities and levels in plasma and whole blood of HP women were consistently moderately lower, and much more significantly lower in RM patients when both were compared to those seen in NP women (P<0.05 and P<0.001, respectively). Furthermore, whereas plasma antioxidant activities and levels were significantly lower in RM patients, those of whole blood and placental tissue were much more significantly lower when compared with HP women (P<0.001). Concurrent with these findings there were consistent increases of equal statistical significance and magnitude in the levels of all investigated oxidants assayed in all samples when compared in between subjects of the study as indicated above. Data thus illustrated a distinct shift in favor of oxidative reactions and reactive oxygen species (ROS) generation, and very significant decreases in the GSH/GSSG ratios in whole blood and placental tissue of RM patients when compared to HP and NP women (P<0.001). The above noted oxidative stress could have been a major causative factor of recurrent miscarriage.

Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells.

Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide)-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting.

Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood.

Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the association between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother-placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR-RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborn's placentas and umbilical cord bloods.

Asherman syndrome in a Danish population.

Intrauterine adhesions (Asherman syndrome) are rare and mainly seen after delivery or abortion in the presence of retained placental tissue. This descriptive study aimed to identify common risk factors for intrauterine adhesions. In a 10-year period 61 women were identified with intrauterine adhesions. The pathology was suspected from symptoms, ultrasonography or on hysterosalpingography, but a final diagnosis could only be given after hysteroscopy. There was no definite evidence regarding methods for prevention and treatment of the disorder. It seems, however, that a conservative approach to curettage, hysteroscopic removal of retained tissue, and the use of distending media are important, together with gentle tissue handling when such procedures are required.

Biocompatible Human Placental Extracellular Matrix Derived Hydrogels.

Solubilizing extracellular matrix (ECM) materials and transforming them into hydrogels has expanded their potential applications both in vitro and in vivo. In this study, hydrogels are prepared by decellularization of human placental tissue using detergent and enzymes and by the subsequent creation of a homogenized acellular placental tissue powder (P-ECM). A perfusion-based decellularization approach is employed using detergent and enzymes. The P-ECM with and without gamma irradiation is then utilized to prepare P-ECM hydrogels. Physical and biological evaluations are conducted to assess the suitability of the P-ECM hydrogels for biocompatibility. The decellularized tissue has significantly reduced cellular content and retains the major ECM proteins. Increasing the concentration of P-ECM leads to improved mechanical properties of the P-ECM hydrogels. The biocompatibility of the P-ECM hydrogel is demonstrated through cell proliferation and viability assays. Notably, gamma-sterilized P-ECM does not support the formation of a stable hydrogel. Nonetheless, the use of HCl during the digestion process effectively decreases spore growth and bacterial bioburden. The study demonstrates that P-ECM hydrogels exhibit physical and biological attributes conducive to soft tissue reconstruction. These hydrogels establish a favorable microenvironment for cell growth and the need for investigating innovative sterilization methods.