In this study, we performed small RNA library sequencing using human placental tissues to identify placenta-specific miRNAs. We also tested the hypothesis that human chorionic villi could secrete miRNAs extracellularly via exosomes, which in turn enter into maternal circulation. By small RNA library sequencing, most placenta-specific miRNAs (e.g., MIR517A) were linked to a miRNA cluster on chromosome 19. The miRNA cluster genes were differentially expressed in placental development. Subsequent validation by real-time PCR and in situ hybridization revealed that villous trophoblasts express placenta-specific miRNAs. The analysis of small RNA libraries from the blood plasma showed that the placenta-specific miRNAs are abundant in the plasma of pregnant women. By real-time PCR, we confirmed the rapid clearance of the placenta-specific miRNAs from the plasma after delivery, indicating that such miRNAs enter into maternal circulation. By using the trophoblast cell line BeWo in culture, we demonstrated that miRNAs are indeed extracellularly released via exosomes. Taken together, our findings suggest that miRNAs are exported from the human placental syncytiotrophoblast into maternal circulation, where they could target maternal tissues. Finally, to address the biological functions of placenta-specific miRNAs, we performed a proteome analysis of BeWo cells transfected with MIR517A. Bioinformatic analysis suggests that this miRNA is possibly involved in tumor necrosis factor-mediated signaling. Our data provide important insights into miRNA biology of the human placenta.

Abstract-In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-␤) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant women at 20 to 23 and 27 to 30 weeks of gestation before PE onset compared with those with normal pregnancies. The sensitivities/specificities for predicting PE at 20 to 23 and 27 to 30 weeks of gestation were 0.75/0.67 (cutoff valueϭ21.9 ng/mL) and 0.88/0.51 (cutoff valueϭ30.5 ng/mL), and the odds ratios were 6.09 (95% CI: 2.35-15.77) and 7.83 (95% CI: 1.70 -36.14), respectively. We conclude that HSD17B1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placenta and that reducing plasma level of HSD17B1 precedes the onset of PE and is a potential prognostic factor for PE. (Hypertension. 2012;59:265-273.) • Online Data Supplement Key Words: preeclampsia Ⅲ microRNA Ⅲ biomarker Ⅲ placenta Ⅲ prospective cohort study T he pathophysiology and etiology of preeclampsia (PE) remain largely unknown, and its final diagnosis can only be made when symptoms have regressed after delivery. 1 Thus, it is of clinical significance to predict PE before its onset. Dysregulation of the serum levels of angiogenic/ antiangiogenic factors has been demonstrated previously; examples include placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin. [2][3][4] However, these proteins may not sufficiently characterize the clinical features and pathophysiological mechanisms of PE onset. 5 If there are any other parameters of which serum levels change in PE, they may illustrate the pathophysiology of PE in a manner different from the previous studies.MicroRNAs (miRNAs), small noncoding RNAs of Ϸ22 nucleotides in length, play a critical role in posttranscriptional gene regulation. 6,7 Although many miRNAs are ubiquitously expressed in mammals, some miRNAs exhibit specific expression patterns in an organ-or cell-type-dependent manner. 8 For instance, miRNAs derived from the miRNA cluster in human chromosome 19, a primate-specific miRNA cluster encompassing 46 miRNAs in the human genome, 9 have been demonstrated to exhibit a placenta-specific expression pattern. 10 Although a few studi...

For cesarean hysterectomy with placenta previa accreta, "universally achievable" measures are required. We propose eight measures: (i) placement of intra-iliac arterial occlusion balloon catheters; (ii) placement of ureter stents; (iii) "holding the cervix" to identify the site to be transected; (iv) uterine fundal incision; (v) avoidance of uterotonics; (vi) "M cross double ligation" for ligating the ovarian ligament; (vii) "filling the bladder" to identify the bladder separation site and "opening the bladder" for placenta previa accreta with bladder invasion; and (viii) to continue to clamp the medial side of the parametrium or the cervix or employment of the "double edge pick-up" to ligate it. These eight measures are simple, easy, effective, and thus "universally achievable".

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Shubnikov de Haas(SdH) oscillations have been measured for the semiconducting single domain SrTiO3 with Carrier concentration of 3.4×1018 cm-3 and 5.9×1018 cm-3. From the temperature dependence of the SdH amplitude, the cyclotron mass values are determined for the [001] and [110] magnetic field directions. We have found, from the angular dependence of the SdH oscillation, that there exist several branches of the frequencies among which the highest and lowest branches originate from the Fermi spheres at the Brillouin zone center, and the other ones from the extremal area which is interconnected through the magnetic breakdown tunneling paths. Energy band parameters based on the k p perturbation method are determined.