Placentation and tumorigenesis have many common features. Human placentation builds a maternal-fetal connection, circumvents maternal immune rejection of the fetus, and utilizes mechanisms that support tumorigenesis, such as proliferation, invasion, angiogenesis, and immune tolerance. Trophoblasts of the human placenta mimic the behavior of malignant cells, proliferating and invading the uterine decidua until reaching the myometrium and remodeling the spiral arteries that establish a new vascular system and escape the maternal immune response. These processes are under precise temporal and spatial regulation, and their dysregulation is associated with different pregnancy syndromes, including preeclampsia (PE), a pregnancy syndrome that is the leading cause of maternal and perinatal mortality and morbidity. At present, the precise mechanisms underlying the development of PE remain unclear. Here, we summarize and dissect the features between physiological placentation and pathological tumorigenesis to explore the pathogenesis of PE - which we believe to be the result of insufficient placentation, compared to the overaggression of tumorigenesis - to provide novel strategies to prevent and treat PE.

Objective::Placental dysfunction is a major contributor to miscarriages in humans. We observed elevated expression of Kruppel-like factor 12 (KLF12) in placental villi of women who experienced miscarriage compared to that in women with healthy pregnancies. This study aimed to elucidate the role of KLF12 in maintaining a successful pregnancy.Methods::To investigate the role of KLF12 in placentation, we employed a model of forskolin-induced syncytialization in BeWo cells.Results::Our findings revealed that KLF12 expression is downregulated during normal syncytialization. Conversely, we observed that abnormally high KLF12 levels directly suppressed glial cells missing-1 ( GCM1) expression. This suppression of GCM1 expression subsequently impaired BeWo cell syncytialization. Furthermore, we observed placental deformities in KLF12-overexpressing mouse fetuses. Conclusion(s)::This study demonstrated that elevated levels of KLF12 disrupt trophoblast syncytialization by downregulating GCM1 expression. These findings suggest that KLF12 may be a novel candidate gene contributing to unexplained miscarriages.

Objective:Advances in genomics and molecular biology have led to the discovery of a large group of uncharacterized long noncoding RNAs (lncRNAs).Emerging evidence indicated that many lncRNAs function in multiple biological processes and its dysregulation often causes diseases.Recent studies suggested that almost all regulatory lncRNAs interact with biological macromolecules such as DNA,RNA,and protein.LncRNAs regulate gene expression mainly on three levels,including epigenetic modification,transcription,and posttranscription,through DNA methylation,histone modification,and chromatin remodeling.LncRNAs can also affect the development of diseases and therefore be used to diagnose and treat diseases.With new sequencing and microarray techniques,hundreds oflncRNAs involved in reproductive disorders have been identified,but their functions in these disorders are undefined.Data Sources:This review was based on articles published in PubMed databases up to July 10,2017,with the following keywords:"long noncoding RNAs","LncRNA","placentation",and "reproductive diseases".Study Selection:Original articles and reviews on the topics were selected.Results:LncRNAs widely participate in various physiological and pathological processes as a new class of important regulatory factors.In spermatogenesis,spermatocytes divide and differentiate into mature spermatozoa.The whole process is elaborately regulated by the expression of phase-specific genes that involve many strains of lncRNAs.Literature showed that lncRNA in reproductive cumulus cells may contribute to the regulation of oocyte maturation,fertilization,and embryo development.Conclusions:LncRNA has been found to play a role in the development of reproduction.Meanwhile,we reviewed the studies on how lncRNAs participate in reproductive disorders,which provides a basis for the study of lncRNA in reproduction regulation.

目的 探讨不同超声图像特征在胎盘植入诊断中的应用价值.方法 回顾性分析2016年4月至2017年7月中南大学湘雅医院分娩的112例产前超声诊断为前置胎盘患者的超声声像图.所有患者均经手术病理确诊.以手术病理结果作为金标准,计算各超声图像特征诊断胎盘植入的敏感度、特异度、阳性预测值、阴性预测值;以手术结果作为金标准,计算各超声图像特征预测胎盘植入患者产后子宫切除的敏感度、特异度、阳性预测值、阴性预测值.结果 本组112例产前超声检查诊断为前置胎盘患者,手术病理结果确诊为胎盘植入71例,非胎盘植入41例,产前超声诊断准确72例,诊断准确率为64.1%.以手术病理结果作为金标准,胎盘后间隙消失、肌层菲薄或消失、胎盘内虫蚀样腔隙、胎盘后方或胎盘与膀胱间血流信号丰富诊断胎盘植入的敏感度分别为83.10%、64.79%、43.66%、64.79%,特异度分别为29.27%、73.17%、87.80%、58.54%、阳性预测值分别为67.05%、80.70%、86.11%、73.02%,阴性预测值分别为50.00%、54.55%、47.37%、48.98%.胎盘后间隙消失诊断胎盘植入的敏感度最高,特异度最低;而胎盘内虫蚀样腔隙诊断胎盘植入的特异度最高.以手术结果作为金标准,胎盘后间隙消失、肌层菲薄或消失、胎盘内虫蚀样腔隙、胎盘后方或胎盘与膀胱间血流信号丰富预测胎盘植入患者产后子宫切除的敏感度分别为100%、77.78%、61.11%、83.33%,特异度分别为25.53%、54.26%、73.40%、48.94%,阳性预测值分别为20.45%、24.54%、30.56%、23.81%,阴性预测值分别为100%、92.73%、90.79%、93.88%.胎盘后间隙消失预测胎盘植入患者产后子宫切除的敏感度较高,但是特异度低;胎盘内虫蚀样腔隙预测胎盘植入患者产后子宫切除的敏感度、特异度均较高.结论 超声检查在产前诊断胎盘植入有重要的价值,其中胎盘后间隙消失敏感度高诊断胎盘植入特异度低,而胎盘内虫蚀样腔隙诊断胎盘植入特异度高,且与前置胎盘患者妊娠结局有一定关联.对于有剖宫产史的前置胎盘患者应行规范化胎盘超声检查,提高胎盘植入的检出率.

The placenta is crucial for a successful pregnancy and the health of both the fetus and the pregnant woman. However, how the human trophoblast lineage is regulated, including the categorization of the placental cell subtypes is poorly understood. Here we performed single-cell RNA sequencing (RNA-seq) on sorted placental cells from first- and second-trimester human placentas. New subtypes of cells of the known cytotrophoblast cells (CTBs), extravillous trophoblast cells (EVTs), Hofbauer cells, and mesenchymal stromal cells were identified and cell-type-specific gene signatures were defined. Functionally, this study revealed many previously unknown functions of the human placenta. Notably, 102 polypeptide hormone genes were found to be expressed by various subtypes of placental cells, which suggests a complex and significant role of these hormones in regulating fetal growth and adaptations of maternal physiology to pregnancy. These results document human placental trophoblast differentiation at single-cell resolution and thus advance our understanding of human placentation during the early stage of pregnancy.

Zearalenone (ZEA) is produced by Fusarium species and a common contaminant in food.ZEA and its metabolites, α-and β-zearalenol, α-andβ-zearalanol, and zearalanone, are mycoestrogens that can interfere with estrogen signaling.High levels of mycoestrogens reduced femalefertility in farm animals and rodents, in which adverse effects of mycoestrogens on major events in female reproduction, including ovarianfolliculogenesis, ovulation, ovarian steroidogenesis, fertilization, preimplantation embryo development and transport, embryo implantation,placentation, parturition, and lactation, have been reported in different experimental settings.Here, we review the in vivo effects ofmycoestrogenson the main events in female reproduction.

Objective:Adequate extravillous trophoblast (EVT) invasion plays a crucial role in the establishment of successful pregnancy.Insufficient trophoblast migration and invasion can result in defective placentation, which is associated with a number of clinical pathological conditions of pregnancy including spontaneous abortion and preeclampsia.Galectin-9 (Gal-9) has a wide variety of regulatory functions in innate and adaptive immunity during infection, tumor growth, and organ transplantation.Methods:We utilized immortalized human first-trimester EVT cells (HTR8/SVneo) for our functional study.We examined the effects of Gal-9 on viability, proliferation, and invasion of HTR8/SVneo cells, as well as on matrix metalloproteinase-2 (MMP-2) production in HTR8/SVneo cells.Furthermore, we observed the effects of different MAPK-signaling pathway inhibitors on the stimulatory functions of Gal-9 on HTR8/ SVneo cells' invasion.Results:We verified the secretion of Gal-9 by trophoblasts and detected a correlation between low levels of Gal-9 and spontaneous abortion.Gal-9 promoted the invasion of HTR8/SVneo cells through its interaction with Tim-3, not CD44, and subsequently increased MMP-2 production.Blockade of p38 signaling pathway inhibited Gal-9 activities in HTR8/SVneo cells.Conclusion:Gal-9 promotes human trophoblast cell invasion through MMP-2 and p38 signaling pathway in a Tim-3-dependent manner.

成功妊娠并孕育健康后代有赖于发育完善的胎盘,胎盘发育障碍是多种妊娠并发症的主要诱因.胎盘是迄今认识最为不足的器官,其形成、发育和功能调节机制,及其与妊娠并发症的分子关联还远未阐明,因而是探究生命孕育机制研究中最为薄弱的一个环节.随着现代生物学技术的发展,人类对胎盘的认识正在从简单的组织结构层面上升到细胞、分子层面,并逐渐走向组学和系统生物学时代.近年来,胎盘发育领域的研究取得了多项开创性成果.本文将分析近期胎盘发育相关的突破性成果,介绍这一领域重要的国际资助计划,并展望未来的发展前景.

Laeverin(LVRN)was first detected on the outer layer of the chorion laeve and migrating extrav-illous trophoblasts(EVTs).It is an enzyme that plays an important role in the placentation and pathophysiology of preeclampsia(PE).Previous studies have indicated that LVRN may be required for the invasion of human trophoblast cells.Paradoxically,LVRN was found to be highly expressed in the trophoblasts of PE patients with impaired invasive capacities.In this study,we detected the expression of LVRN in the placentas of PE patients(n=5)and normal term pregnancy women(n=5)as a control group by immunohistochemistry.LVRN was elevated in decidua(P=0.0083)and villi(P=0.0079)of PE patients.Next,LVRN was overexpressed via adeno-associated virus-mediated gene transfer in trophoblastic cell lines HTR8,Swan71,and JAR.Matrigel transwell assay and wound healing assay showed that overexpression of LVRN impeded the invasion of these three cell lines.Western blot analysis showed that LVRN overexpression caused downregulation of N-cadherin and vimentin and upregulation of E-cadherin,suggesting the inhibitory role of LVRN in epithelial-mesenchymal transition(EMT).Moreover,our data indicated that long noncoding RNA NONSTAT103348(Inc10-7)was elevated in PE patients.Silencing Inc10-7 led to decreased LVRN expression.Taken together,although the basal level of LVRN may be crucial for cell invasion,over-expression of LVRN may abrogate the cell invasiveness,suggesting a multifaceted role of LVRN in the pathogenesis of PE.

Preeclampsia(PE)is characterized by placenta-mediated pregnancy complication.The only effective treatment for PE is the delivery of the placenta.However,this treatment may cause preterm birth and neonatal death.Therefore,preventing PE is needed.The mechanism of PE involves abnormal placentation,which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation.These mediators contribute to systemic vascular dysfunction,inflammatory responses,and excessive thrombin generation.Microparticles(MPs)are reportedly involved in PE by promoting the thromboinflammatory response.This study describes a strategy to prevent PE by reducing MP release using the recombinant protein,diannexin.Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation.Additionally,diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells.Moreover,in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice.Furthermore,diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro.These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.