BNIP3和缺氧诱导因子1在妊娠期高血压疾病患者胎盘组织中的表达

妊娠期高血压疾病是导致孕产妇及围生儿死亡的主要原因之一。滋养细胞浅着床、胎盘血管重塑障碍致胎盘灌注不足是妊娠期高血压疾病发病的关键环节。缺氧可使滋养细胞浸润过浅，子宫螺旋动脉重塑不良，使胎盘缺血缺氧，导致妊娠期高血压疾病的发生。     

子痫前期发病机制研究进展

子痫前期是一种妊娠期特有疾病,滋养细胞对子宫螺旋动脉重塑障碍可能是子痫前期发病的根本原因,滋养细胞本身异常,以及滋养细胞与其所处微环境相互作用异常都可以导致滋养细胞重塑功能障碍;子痫前期临床表现是功能异常的胎盘释放到母体循环中的一些因子所引起,血管内皮生长因子1可溶性受体是最重要的子痫前期因子之一,有可能成为子痫前期早期诊断新指标.     

子痫前期发病机制研究进展

子痫前期是一种妊娠期特有疾病，滋养细胞对子宫螺旋动脉重塑障碍可能是子痫前期发病的根本原因，滋养细胞本身异常，以及滋养细胞与其所处微环境相互作用异常都可以导致滋养细胞重塑功能障碍：子痫前期临床表现是功能异常的胎盘释放到母体循环中的一些因子所引起，血管内皮生长因子1可溶性受体是最重要的子痫前期因子之一，有可能成为子痫前期早期诊断新指标。     

蜕膜自然杀伤细胞在妊娠并发症中的作用研究进展

蜕膜自然杀伤（dNK）细胞是存在于母胎界面并与胎儿滋养层细胞密切接触的免疫细胞。dNK细胞可能通过分泌相关细胞因子在母胎耐受、螺旋动脉重铸、血管形成以及妊娠期并发症的发生中发挥重要作用。近年来研究发现dNK细胞与正常妊娠的发生及维持密切相关,并发现妊娠期并发症如复发性自然流产、子痫前期等普遍存在dNK细胞细胞学及免疫学等方面的异常改变。综述近年来dNK细胞的最新研究,包括数量、表型、分泌的相关细胞因子及血管生成因子等,以及dNK细胞在妊娠并发症发病中的可能机制。     

合并胎儿宫内发育迟缓的初产妇和经产妇外周血淋巴细胞分类计数

ＬｏｓｅＬ，ｅｔａｌＥｕｒｏｐＪＯｂｓｔｅｔ＆Ｇｙｎｅｃｏｌ，１９９９，８２：２３妊娠是母体对胎儿同种移植物免疫耐受的特殊阶段。如蜕膜细胞免疫被激活，将限制滋养细胞的种植，导致血管内膜滋养细胞深入肌层不良及螺旋动脉自主神经支配失调，成为自然流产、先兆...     

金属基质蛋白酶-26在妊娠早期和中期原代细胞滋养细胞中的表达

在早孕期间 ,胚胎植入对成功妊娠的意义重大 ,胚胎植入开始于绒毛内细胞滋养细胞向子宫肌层浸润 ,正确的胎盘滋养细胞浸润是要求绒毛滋养细胞侵入子宫蜕膜深达螺旋动脉的过程 ,在时间和空间上有严格的调控[1] 。胎盘植入过程调控异常可能会导致异常妊娠 ,如流产、胎儿生长受限、妊娠高血压综合征或滋养细胞肿瘤。金属基质蛋白酶(MMPs)是一族Zn 依赖性蛋白酶 ,具有分解连接组织的能力 ,胚胎植入过程中MMPs有助于滋养细胞穿过基质和侵蚀 ,MMP 2 6是最近才被认识和克隆的金属基质蛋白酶[2 ] ,本实验采用高纯度的原代细胞滋养细胞体外培养…     

母胎界面的异常与胎盘植入发生的关系

胎盘植入是产科严重并发症,目前其发病机制尚未明确。良好的母胎界面是顺利妊娠的保证。蜕膜原发性或继发性缺陷、子宫胎盘新生血管的异常形成、滋养细胞过度浸润蜕膜甚至子宫肌层,均可能导致胎盘植入的发生。蜕膜缺陷、滋养细胞入侵可能是单独起作用,但近年多方面的机制共同作用更为广大研究者认同。现就正常蜕膜、滋养细胞入侵、血管形成及其与胎盘植入的关系进行综述。     

胎盘缺血与胎盘早剥

胎盘早剥是是妊娠晚期的严重并发症之一,处理不当可危及母儿生命。胎盘的缺血性损伤被认为是胎盘早剥的最初原因。胎盘缺血性损伤导致了滋养细胞侵袭能力的改变及子宫螺旋小动脉发生的重塑障碍,胎盘缺血、缺氧后释放各种细胞因子造成蜕膜坏死、血管破裂、出血,而出血导致底蜕膜和胎盘之间形成撕裂和分离,进而造成蜕膜板和胎盘的分离。进一步造成更多的血管破裂、动脉出血和胎盘后血肿,最后导致胎盘早剥的发生。     

宫腔镜在治疗剖宫产疤痕处妊娠的临床价值

<正>剖宫产术后疤痕处妊娠(cesarean scar pregnancy,CSP)是受精卵、滋养叶细胞种植于前次剖宫产切口瘢痕处,被子宫肌纤维及瘢痕纤维组织所完全包绕,是一种罕见而危险的异位妊娠。胚胎着床于瘢痕部位可发生底蜕膜缺损,滋养细胞可侵入子宫肌层生长,绒毛与子宫肌层粘连、植入甚至穿透子宫壁,随着妊娠进展可导致子宫破裂及大出血。因此,     

子宫巨噬细胞在正常妊娠及病理性妊娠中的作用

巨噬细胞（macrophages）是妊娠期母体子宫蜕膜中数量第二丰富的淋巴细胞,可分泌多种具有抗炎和促炎作用的细胞因子和趋化因子。巨噬细胞除作为主要抗原呈递细胞参与蜕膜免疫外,还在母胎界面免疫耐受的建立和维持、滋养细胞侵入、血管生成和螺旋动脉重塑以及凋亡细胞的吞噬中发挥关键作用。因此,巨噬细胞的细胞数量、极化和功能异常与妊娠并发症如流产、子痫前期和早产等密切相关。综述近年子宫巨噬细胞极化、功能及其在正常妊娠建立、维持和病理性妊娠中作用机制的最新研究进展,以期为从免疫角度探讨病理性妊娠发病机制及研发精准防治策略提供新的思路。     

胎盘外泌体在子宫螺旋动脉重铸不全相关妊娠并发症中的作用

子宫螺旋动脉重铸是胎盘滋养细胞与母体血管内皮、平滑肌细胞、免疫细胞等相互作用下完成的,细胞间信息传递在这一过程中起重要作用。外泌体的发现更新了学者们对细胞间信息传递的思考模式。外泌体是细胞主动分泌的直径40~100 nm的囊泡,可由多种细胞分泌并可从多种体液中分离出来,携带多种蛋白质、mRNA、微小RNA(miRNA)等信号分子,在细胞间通讯起重要作用。研究证明,胎盘滋养细胞能分泌外泌体,在母血中能检测并分离出胎盘外泌体,胎盘外泌体携带滋养细胞信息,作用于母体细胞,调节血管形成,重铸子宫螺旋动脉,调节母体免疫,参与胎盘屏障的形成。综述胎盘外泌体的特征、生物学功能及其在螺旋动脉重铸不全相关妊娠并发症中的变化,探讨胎盘外泌体作为诊断妊娠并发症血清标志物的临床价值。     

子宫螺旋动脉重铸与病理妊娠

子宫螺旋动脉重铸是妊娠正常进行的关键环节,绒毛外滋养细胞的增殖和侵袭是血管重铸过程的必要条件。滋养细胞生物学功能的完整和调控机制的协调起着至关重要的作用。滋养细胞浸润不足,栓塞螺旋动脉不彻底,母-胎循环的发生提前,使绒毛受到直接的机械损伤,氧化应激作用间接地造成细胞机能障碍和损伤,出现胎盘退化变性;人肿瘤蛋白p53(TP53)介导细胞通路对细胞周期蛋白依赖性激酶抑制剂1A(CDKN1A)和Bax基因的异常表达,微小RNA-520(miR-520)过度调控滋养细胞的凋亡导致母体出现复发性流产。由滋养细胞分泌产生的基质金属蛋白酶9(MMP-9)的异常表达和大量炎性因子的释放造成了胎盘缺血缺氧,表现出子痫前期的相关症状。胎盘绒毛的血管密度、绒毛间隙体积的降低、滋养细胞分化程度下降、微环境缺氧以及突触缺陷因子1(SYDE1)呈低水平表达,可能是造成胎儿生长受限的重要原因。因此研究螺旋动脉重铸过程对病理妊娠的早期诊治有着重要意义。     

dNK derived IFN-γ mediates VSMC migration and apoptosis via the induction of LncRNA MEG3: A role in uterovascular transformation

IntroductionAppropriate spiral artery remodeling is critical for successful fetal development and pregnancy outcomes. The vascular smooth muscle cell (VSMC) loss and separation, involving cell apoptosis and migration, plays an important role in this process. Decidual natural killer cells (dNK)-derived interferon gamma (IFN-γ), a key regulator of uterine arterial remodeling, can facilitate separation of VSMC layers, however, the specific mechanisms of it action are unknown. Long non-coding RNA MEG3 functions as tumor suppressor by regulating apoptosis and migration. Moreover, IFN-γ has been shown to influence cell vitality through regulating MEG3 expression. However, the functional role of dNK derived IFN-γ and MEG3 on VSMC viability, as well as the relationship between IFN-γ and MEG3 in VSMCs, has not been completely elaborated.MethodsThe up-regulation strategies and reagent treatment were employed to detect the effects of MEG3 and dNK/IFN-γ on VSMC proliferation, apoptosis and migration. At the same time, MEG3, p53 and matrix metalloproteinase 2 (MMP-2) expressions were investigated.Results: dNK/IFN-γ treatment led to up-regulation of MEG3 expression in VSMCs. Both MEG3 over-expression and dNK/IFN-γ treatment inhibited VSMC proliferation, stimulated VSMC migration and resulted in a small but significant induction of VSMC apoptosis, as well as promoted p53 and MMP-2 expression in VSMCs.DiscussionMEG3 is regulated by dNK-derived IFN-γ and regulates VSMC migration and apoptosis. Therefore, it may be an important positive regulator in VSMC loss from the maternal uterine spiral arteries during vascular transformation.     

子宫螺旋动脉重铸障碍在复发性流产中的研究进展

复发性流产是一种常见的病理妊娠,其病因和发病机制至今尚未完全阐明。足够的子宫胎盘血供对于正常妊娠是至关重要的,这有赖于广泛的子宫螺旋动脉生理性重铸所形成高流量、低阻力的母胎血液循环系统。子宫螺旋动脉血流反映母胎之间的血液循环,是子宫与妊娠母体的终末分支,能提供充足的胎盘血流和养分,满足胚胎的生长发育。滋养细胞的侵袭及其介导的子宫螺旋动脉细胞的凋亡是重铸过程的两个关键环节,若重铸障碍则胎盘灌注量不足,继而胚胎缺血、缺氧,导致一系列病理妊娠。早期研究表明复发性流产患者蜕膜组织中滋养细胞侵袭减少,螺旋动脉重铸障碍,因此对复发性流产这一特征性病理改变产生的研究成为阐明病因的关键。     

Secretion of Angiogenic Growth Factors by Villous Cytotrophoblast and Extravillous Trophoblast in Early Human Pregnancy

Angiogenesis is a key feature of placental and uterine development in early pregnancy. We hypothesized that trophoblast cells produce angiogenic growth factors, and that expression differs between villous cytotrophoblast (CTB) and extravillous trophoblast (EVT) cells. Fourteen angiogenic growth factors were measured by multiplex growth factor analysis or ELISA in tissue culture supernatants from EVT and CTB from pregnancies at 8–10 and 12–14 weeks' gestation. Gestational age and cell type differences were observed. EVT and CTB are major producers of angiogenic growth factors that likely contribute to placental vascular development and spiral artery remodeling.     

In vitro and in vivo evidence for lack of endovascular remodeling by third trimester trophoblasts

The placental-decidual interaction through invading trophoblasts determines whether a physiological transformation of the uterine spiral arteries is established or not. Trophoblast-orchestrated artery remodeling is central to normal placentation. Dysregulated uteroplacental interaction and vascular remodeling are thought to be associated with the molecular events underlying the pathology of late pregnancy anomalies including preeclampsia. Although the exact gestational age at which trophoblast invasion ceases is not known, it remains unclear whether late pregnancy trophoblasts retain the ability to transform the uterine arteries. Here, we have developed a dual cell, in vitro culture system that mimics the vascular remodeling events during normal pregnancy. We demonstrate that first and third trimester trophoblasts respond differentially to interactive signals from endothelial cells when cultured on matrigel. Term primary trophoblasts or immortalized third trimester extravillous TCL1 trophoblasts not only fail to respond to signals from endothelial cells but also inhibit endothelial cell tube formation. In contrast, HTR8 cells, representing a first trimester trophoblast cell line with invasive properties, undergo spontaneous migration and synchronize with the endothelial cells in a capillary network. This disparity in behavior was confirmed in vivo using a matrigel plug assay. Poor expression of VEGF C and VEGF receptors coupled with high E-cadherin expression by term primary trophoblasts and TCL1 cells contributed to their restricted interactive and migratory properties. We further show that the kinase activity of VEGF R2 is essential for proactive crosstalk by HTR8 cells. This unique behavior of first trimester trophoblasts in the presence of endothelial cells offers a potential approach to study cell-cell interactions and to decipher modulatory components in the serum samples from adverse pregnancy outcomes.     

Correlation of first trimester placental volume and second trimester uterine artery Doppler flow

Uterine artery Doppler examination can identify impaired trophoblast invasion in the second trimester of pregnancy. High resistance and an early diastolic 'notch' show insufficient physiological conversion of the spiral arteries. Uterine artery Doppler is routinely performed between 22-24 weeks which is relatively late for treatment. In this study we wanted to find out whether women with increased uterine blood flow resistance at 22 weeks already have reduced placental volumes in the first trimester measured with 3D sonography.A total of 1060 women with singleton pregnancies had three dimensional (3D) volume measurements of their placentae between 11-13 weeks and uterine Doppler scans between 21-22 weeks. Stepwise logistic and linear regression analyses were used to show a correlation between placental volume (PV) and a CRL dependent placental quotient (PQ) with uterine perfusion parameters.Uterine perfusion at 21-22 weeks depends significantly on PV or PQ at 11-13 weeks (P< 0.0001 for both) and smoking behaviour (P=0.006). The occurrence of a notch also depends significantly on PV and PQ (P< 0.0001 for both) and also on gravidity (P< 0.0001) and age (P=0.0007) as well as on smoking behaviour (P=0.0094). PV and PQ did not show any dependency on age, gravidity, BMI or smoking habits. Placentae of women with high resistance uterine perfusion in the second trimester are already remarkably small in the first trimester. Placental volumetry is probably an efficient method for early and simple identification of impaired trophoblast invasion.