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Abstract-Preeclampsia is a major cause of maternal and fetal mortality and morbidity worldwide. The differential expression of several microRNAs (miRNAs) has been found in preeclamptic placentas. However, great conflict exists regarding this aspect, and detailed examinations have largely been lacking of miRNA profiles in different parts of the placenta and in maternal plasma of women with this disorder. In this study, a total of 9 downregulated miRNAs (miR-195, miR-223, miR-218, miR-17, miR-18a, miR-19b1, miR-92a1, miR-379, and miR-411) and 7 upregulated miRNAs (miR-210, miR-30a-3p, miR-518b, miR-524, miR-17-3p, miR-151, and miR-193b) were identified in severe preeclampsia (sPE) placentas when compared with normal pregnant controls. In addition, sampling position in the chorionic or basal plate of placenta led to evident variations in differential miRNAs of sPE placentas. In a prospective pregnant cohort, we found that the circulating levels of 3 members of miR-17-92 cluster (ie, miR-18a, miR-19b1, and miR-92a1) were significantly lower, whereas that of miR-210 was higher in sPE patients than those in normal controls at gestational weeks 15 to 18 and at term. The results of in situ hybridization revealed the localization of miR-18a, miR-92a1, and miR-210 in various subtypes of placental trophoblasts and endothelial cells. In human trophoblast cell line, HTR8/SVneo cells, miR-18a could promote trophoblast cell invasion via targeting and suppressing Smad2 expression. This study provides fundamental evidences for exploring the roles of miRNAs in the pathogenesis of preeclampsia. Variations of MicroRNAs in Human Placentas and Plasma From Preeclamptic Pregnancy Xu et al Differential miRNAs in Preeclampsia 1277modulating effect of miR-18a. The data provide important evidences for exploring the pathogenesis of the disease from a noncoding RNA viewpoint. Materials and MethodsAll the details of the materials and methods are provided in the online-only Data Supplement. Study SubjectsIn this study, the collection of human placenta tissues and plasma specimens was performed with the permission of the local ethical committee in the Institute of Zoology, Chinese Academy of Sciences, and informed consent was obtained from all patients enrolled in this study. Placentas and maternal blood samples from normal pregnant and preeclamptic women were obtained from pregnant women who underwent perinatal care in Peking University Third Hospital from August 2010 to October 2012. Totally 20 severe preeclamptic patients who delivered at 35th to 39th weeks and 33 normal pregnant women who delivered at 37th to 39th weeks were enrolled in this study. Their placentas at deliveries and plasma samples at gestational weeks 15 to 18 and weeks 35 to 38 were used. The clinical characteristics of these women are summarized in Table 1. miRNA Microarray AnalysisLarge-scale profiling of miRNA expression was achieved by mammalian miRNA chip array (V2.0, Capitalbio, Beijing, China), which stems from the miRbase release 8.2 (Wellcome Trust Genome Camp...

Progress in high-throughput MALDI-TOFMS analysis, especially in proteome applications, requires development of practical and efficient procedures for the preparation of proteins and peptides in a form suitable for high acquisition rates. These methods should improve successful identification of peptides, which depends on the signal intensity and the absence of interfering signals. Contamination of MALDI samples with alkali salts results in reduced MALDI peptide sensitivity and causes matrix cluster formation (widely reported for CHCA matrix) observed as signals dominating in the range below m/z 1200 in MALDI spectra. One way to remove these background signals, especially for concentrations of peptides lower than 10 fmol/microL, is to wash matrix/sample spots after peptide cocrystallization on the MALDI plate with deionized water prior to analysis. This method takes advantage of the low water solubility of the CHCA compared to its alkali salts. We report here that the application of some ammonium salt solutions, such as citrates and phosphates, instead of deionized water greatly improves the efficiency of this washing approach. Another way to reduce matrix cluster formation is to add ammonium salts as a part of the MALDI matrix. The best results were obtained with monoammonium phosphate, which successfully suppressed matrix clusters and improved sensitivity. Combining both of these approaches-the addition of ammonium salts in the CHCA matrix followed by one postcrystallization washing step with ammonium buffer-provided a substantial ( approximately 3-5-fold) improvement in the sensitivity of MALDI-MS detection compared to unwashed sample spots. This sample preparation method resulted in improved spectral quality and was essential for successful database searching for subnanomolar concentrations of protein digests.

The present study demonstrates that the BMP-15 level in FF appears to be a potential factor in predicting oocyte quality and subsequent embryo development, and is correlated with E(2) level, which may additionally be a valuable predictor of oocyte fertilization.

OS may inhibit the expression of endometrial integrin beta3 subunit and LIF and impair endometrial receptivity in mice. OS with GnRH agonist, but not GnRH antagonist, may partially restore the endometrial physiological secretion and improve uterine receptivity.

BackgroundEarly pregnancy loss (EPL) is a frustrating clinical problem, whose mechanisms are not completely understood. DNA methylation, which includes maintenance methylation and de novo methylation directed by DNA methyltransferases (DNMTs), is important for embryo development. Abnormal function of these DNMTs may have serious consequences for embryonic development.MethodsTo evaluate the possible involvement of DNA methylation in human EPL, the expression of DNMT proteins and global methylation of DNA were assessed in villous or decidua from EPL patients. The association of maintenance methylation with embryo implantation and development was also examined.ResultsWe found that DNMT1 and DNMT3A were both expressed in normal human villous and decidua. DNMT1 expression and DNA global methylation levels were significantly down-regulated in villous of EPL. DNMT3A expression was not significantly changed in the EPL group compared to controls in either villous or decidua. We also found that disturbance of maintenance methylation with a DNMT1 inhibitor may result in a decreased global DNA methylation level and impaired embryonic development in the mouse model, and inhibit in vitro embryo attachment to endometrial cells.ConclusionsOur results demonstrate that defects in DNA maintenance methylation in the embryo, not in the mother, are associated with abnormal embryonic implantation and development. The findings of the current study provide new insights into the etiology of EPL.

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