microRNA的研究进展

微小核糖核酸(miRNA)是一类长20～22个核苷酸的小分子非编码RNA,它通过与靶基因3'端非翻译序列结合促进靶基因降解或抑制翻译过程,从而抑制靶基因表达。miRNA参与生物体的生长、发育和凋亡的调控,并在疾病发生和发展过程中起着重要作用。现从miRNA的产生、作用机制、在生物体发育和疾病发生中的作用、作为生物学标记的研究进展以及病理状态下在胎盘中的差异表达等方面予以综述。     

胎盘部位过度反应及胎盘部位结节的临床病理分析

目的探讨胎盘部位过度反应及胎盘部位结节的临床病理学特征以及免疫组织化学染色在鉴别诊断中的意义。方法对15例胎盘部位过度反应及4例胎盘部位结节的临床及病理表现进行回顾性研究,并应用人绒毛膜促性腺激素(hCG)、人胎盘催乳素(hPL)、细胞角蛋白(CK)18、胎盘碱性磷酸酶(PLAP)、α-抑制素(inhibin),进行免疫组织化学染色。结果15例胎盘部位过度反应患者的年龄为25～40岁(平均31．5岁),4例胎盘部位结节患者年龄为26～39岁(平均34．3岁)。15例胎盘部位过度反应的组织学特征为：在子宫内膜、子宫肌层及螺旋动脉中有索条状及片状种植部位中间滋养细胞浸润,子宫内膜及肌层的结构没有破坏。4例胎盘部位结节在子宫内膜组织及变性坏死的绒毛间有多个以致密的嗜酸性玻璃样物质为背景的结节性病变,结节内为绒毛膜型中间滋养细胞。15例胎盘部位过度反应对hPL及CK18均呈阳性反应;4例胎盘部位结节均对CK18、α-抑制素及PLAP均呈阳性反应。所有15例胎盘部位过度反应Ki-67增生指数均≤5％。4例胎盘部位结节Ki-67增生指数均为0。结论胎盘部位过度反应及胎盘部位结节的临床及病理形态学特征不同于滋养细胞肿瘤。免疫组织化学染色对鉴别诊断有帮助。     

内皮型一氧化氮合酶运输介导物在子痫前期患者胎盘组织中的定位及定量研究

目的探讨内皮型一氧化氮合酶运输介导物(endothelial n itric oxide synthase traffic inducer,NOSTR IN)在子痫前期(pre-ec lampsia,PE)患者胎盘血管内皮细胞中表达的变化及其在子痫前期发病过程中的作用。方法HE染色后镜下观察胎盘组织及血管的病理变化,免疫组织化学方法及W estern b lot检测子痫前期患者胎盘组织中NOSTR IN的表达。结果HE染色显示子痫前期患者胎盘绒毛血管变细,数目减少,血管合体膜增厚,纤维素样坏死明显多于正常妊娠;免疫组织化学显示正常妊娠和子痫前期患者胎盘血管内皮细胞中都有NOSTR IN的表达,但子痫前期患者胎盘血管内皮细胞胞浆染色较正常妊娠明显增强;W estern b lot显示子痫前期患者胎盘组织中NOSTR IN的表达显著高于正常妊娠(P<0.01)。结论胎盘组织中NOSTR IN表达增加可能是子痫前期发病机制的重要环节之一。     

PLACENTAL CALCIUM PUMP: CLINICAL-BASED EVIDENCE

Placenta can be considered as a pump of calcium necessary for the normal development of the fetus. We believe that the location of this pump is in the placental basement membrane. The calcification of this membrane has been described only in cases of in utero fetal death. In this study we describe for the first time a case of placental calcification in a living fetus. The fetus of a normal 21-year-old pregnant woman showed heart abnormalities but the genetic analysis showed a normal male karyotype. The histology of the placenta demonstrated multiple intravillous linear and granular calcific incrustations The hemtoxylin/eosin stain of the sections revealed basement membrane calcific incrustations and intravillous calcium deposits. We postulate that the fetal circulation in the villi was impaired and the calcium that reached the villi from the mother was deposited at this level.     

Review: Bio-compartmentalization of microRNAs in exosomes during gestational diabetes mellitus

Analysis of the human genome revealed that only 1.2% encoded for proteins, which raised questions regarding the biological significance of the remaining genome. We now know that approximately 80% of the genome serves at least one biochemical function within the cell. A portion of this 80% consists of a family of non-coding regulatory RNAs, one important member being microRNAs (miRNAs). miRNAs can be detected in tissues and biofluids, where miRNAs in the latter can be bound to proteins or encapsulated within lipid vesicles such as exosomes. Gestational diabetes mellitus (GDM) is a complication of pregnancy, which has harmful health impacts on both the fetus as well as the mother. The incidence of GDM worldwide varies, but reached 18% in the HAPO cohort using the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Not only has GDM been associated with increased risks of further complications during pregnancy, but also poses long-term risks for both the mother and the baby. Thus, understanding the pathophysiology of GDM is important from a public health perspective. Literature has demonstrated that GDM is associated with elevated levels of circulating exosomes in maternal circulation. However, there is a paucity of data defining the expression, role, and diagnostic utility of miRNAs in GDM. This review briefly summarizes recent advances in the function and quantification of intracellular and extracellular miRNAs in GDM.     

Placental dimethyl acetal fatty acid derivatives are elevated in preeclampsia

Preeclampsia (PE) was shown to affect the placental content and the transfer of polyunsaturated fatty acids (PUFA) to the fetus. Plasmalogens, a type of phospholipids with a vinyl-ether link at the sn-1 position, play an antioxidant role and are specifically enriched in PUFA at the sn-2 position. In this study, we characterized plasmalogen-derived dimethyl acetal (DMA) fatty acid derivatives, 16:0 DMA, 18:0 DMA, 9c-/11c-18:1 DMA and PUFA in the placenta of normotensive (n = 20) and PE (n = 20) pregnancies, according to the sampling site: peri-insertion or periphery. Phospholipid fatty acids from the placenta and maternal erythrocytes were identified by gas chromatography mass spectrometry and quantified by flame ionization detection. We found elevated total DMA in the PE placenta by 18% when compared to normotensive controls (p = 0.026). Moreover, the 16:0 DMA account for more than 55% of DMA fatty acids measured in the placenta, and its level is significantly higher in PE than controls (p = 0.018). Also, we found elevated placental PUFA, 20:5(n-3), 22:5(n-3) and a low level of 20:4(n-3) in PE compared to controls. Placental DMA was highly correlated with n-6 and n-3 PUFA in both, normotensive and PE pregnancies. In sum, elevated DMA fatty acids in the PE placenta could be an indirect defensive mechanism against oxidative stress and poor placental fatty acid transfer in PE.     

Effect of glucocorticoids on mechanisms of placental angiogenesis

The benefits of antenatal glucocorticoid (GC) treatment to promote human fetal lung maturation are well established. However, reports have emerged indicating that maternal exposure to high concentrations of circulating GCs alters placental and fetal development. Because many adult-onset metabolic and cardiovascular disorders have their origins in utero, the importance of prenatal conditions should be considered in detail. Therefore, this review aims to present an overview of the GC effect on placental and fetal development, specifically with regard to mechanisms of placental angiogenesis.We assumed that GC overexposure affects fetal development by altering placental angiogenesis. Disturbances in the development of the villous tree and pathological changes in the villous vascular system with insufficient uteroplacental blood flow have been linked to the pathogenesis of intrauterine growth retardation. Moreover, low birth weight is a serious risk factor known to correlate with an increased risk of adult-onset diseases. Although there have been many circumstances in which maternal GCs are elevated, we focused on exogenous synthetic GCs that are applied for therapeutic reasons. However, some questions about the use of steroids remain unanswered, which will require further studies that lead us to review alterations in placental angiogenesis under the perspective of GC overexposure.     

The expression level of C19MC miRNAs in early pregnancy and in response to viral infection

IntroductionWe have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo.MethodsWe prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR. To examine the effect of viral exposure on C19MC miRNAs expression, we used three systems: (1) a transgenic mouse overexpressing the C19MC cluster and exposed to Togaviridae during pregnancy, (2) cultured primary human trophoblasts exposed to Vesicular Stomatitis Virus in vitro, and (3) amniotic fluid from women exposed to cytomegalovirus during pregnancy.ResultsIn 27 IVF pregnancies, C19MC miRNAs were detected as early as 2 weeks after implantation, and their levels increased thereafter. There was no change in C19MC miRNA expression levels in the mouse placenta in response to viral exposure. Similarly, Vesicular Stomatitis Virus infection of primary human trophoblast did not selectively increase C19MC miRNA expression. C19MC miRNA expression in the amniotic fluid was not affected by vertical transmission of cytomegalovirus.DiscussionThe expression of C19MC miRNAs in maternal circulation very early in pregnancy suggests a role in the establishment of the maternal-fetal interface. The levels of C19MC miRNA are not influenced by diverse types of viral infection.