蜕膜巨噬细胞与滋养细胞凋亡在子痫前期发病中的潜在作用

子痫前期是产科常见且严重的妊娠并发症，是导致围产儿及孕产妇死亡的重要原因[1]，其确切发病机制至今仍不清楚。其发病机制的假说很多，普遍认为胎盘在其发生与发展中起着重要作用[2]。滋养细胞的增殖、分化及凋亡是胎盘形成过程中必不可少的步骤[3]。蜕膜巨噬细胞作为清除凋亡成分的主要细胞[4]，若其功能异常，必将影响滋养细胞的增殖和分化，妨碍胎盘的形成，最终导致子痫前期的发生。现就蜕膜巨噬细胞和滋养细胞凋亡在子痫前期发病中的潜在作用进行综述。     

子宫自然杀伤细胞在胚胎着床期功能的研究进展

子宫自然杀伤(u NK)细胞是存在于女性子宫中的一类特殊的免疫细胞,表型主要为CD~(56bright) CD16~-,在正常妊娠早期表现为强大的免疫调节功能及相对较弱的细胞毒性,其在胚胎着床过程中有着重要的作用,包括细胞因子及生长因子的分泌,促进滋养层细胞入侵蜕膜以及蜕膜和胎盘的血管生成等。u NK细胞功能及数量的异常被认为与多种妊娠相关疾病有关,如复发性流产、子痫前期等。本综述目的在于汇总对子宫自然杀伤细胞的最新研究,将有助于了解这些疾病的发病机制,最终指导临床的预防与治疗。     

母胎界面免疫调节与子痫前期关系的研究进展

子痫前期是妊娠期特发性疾病,可累及全身各器官系统,严重威胁母儿健康,患者远期罹患心血管疾病、肾脏疾病等风险也显著增加,但病因及发病机制尚不明确,因而目前尚无有效的防治措施。现已明确,母胎界面免疫活性细胞及免疫分子的相互作用、免疫调节机制的异常可直接导致滋养细胞的浅着床、螺旋动脉重铸障碍,从而在子痫前期的发病机制中起着重要作用。     

ACVR2A与子痫前期相关性研究进展

子痫前期是一种妊娠特异性疾病,是孕产妇和围生期死亡的主要原因。至今尚无任何一种假说可以彻底地解释子痫前期的病理变化,目前比较公认的特征是早期胎盘滋养细胞浸润和螺旋动脉重铸减少。ACVR2A(activin A receptor type 2A)是转化生长因子β(TGF-β)受体家族的成员,被认为是生殖功能的重要调节因子,尤其是在蜕膜化、滋养细胞浸润和胎盘形成过程中起重要作用。近些年的研究表明激活素A及其受体在子痫前期的发生、发展过程中有重要的调控作用。综述ACVR2A与子痫前期的关系,旨在为子痫前期的发病机制、早期诊断及治疗提供新的理论依据。     

HtrA与子痫前期相关性的研究进展

子痫前期(preeclampsia)是妊娠期特有的疾病,目前仍是重要的公共卫生问题,是发展中国家孕产妇死亡的主要原因之一。研究表明子痫前期与细胞凋亡、血管痉挛、凝血系统激活、炎症反应等密切相关,其病理变化起始于胎盘浅着床和胎盘血管重铸障碍,导致胎盘组织的缺血缺氧,引起子痫前期的发生。HtrA(high temperature requirement A)系丝氨酸蛋白酶家族,该蛋白家族在细胞热休克、氧化应激、炎症、缺血再灌注和肿瘤等应激条件下,降解细胞胞质内错误折叠的蛋白质,参与细胞凋亡、关节炎、胚胎形成、神经变性和神经肌肉障碍以及癌症等的病理生理过程,研究表明其亚型与子痫前期密切相关。总结近年来与子痫前期有关的HtrA的研究进展及其介导的调控网络,对进一步了解子痫前期的发病机制及提供新的治疗途径有重要意义。     

子痫前期胎盘因素在胎儿生长受限中的作用

胎儿生长受限(FGR)为子痫前期最常见的并发症,子痫前期和胎儿生长受限的发病基础有共同之处,与胎盘浅着床代偿性分泌一系列异常活性因子有关,并引发胎盘功能不良、胎儿生长受限等妊娠不良结局。近年许多实验着力于进一步研究子痫前期血管生长因子、胎盘内分泌激素及细胞因子的表达差异与FGR发生的相关性,为子痫前期的病情发展及预测妊娠结局和治疗提供新的依据。     

子宫内膜蜕膜化调节机制的研究现状

子宫内膜蜕膜化是子宫为了适应妊娠而做出的最早改变之一。围着床阶段,子宫内膜在生化、细胞、生理及功能等各个水平发生了复杂变化,使得自身具有可接受性,能为胚胎着床及生长提供合适的微环境。多种激素、细胞因子、转录因子、免疫细胞等参与调节子宫内膜间质细胞向蜕膜细胞的转变。     

蜕膜NK细胞与妊娠关系的研究进展

自然杀伤细胞(NK cells)是天然免疫系统的重要组成部分。蜕膜NK细胞作为妊娠早期出现最多的淋巴细胞,其表型和功能具有独特性。在母胎界面,蜕膜NK细胞一般处于抑制状态,通过维持滋养层侵袭、血管重塑及胚胎耐受等参与正常妊娠过程。蜕膜NK细胞数量、亚型、毒性、受体及细胞因子等的变化可能导致复发性流产、子痫前期等病理妊娠的发生。     

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。     

子痫前期发病机制的研究进展

子痫前期（preeclampsia）发病率高,进展迅速,是一种累及母体多系统的妊娠期高血压综合征。据统计,子痫前期每年可导致全球超过7万孕妇和50万胎儿死亡,给全球的医疗卫生保健系统造成严重的负担。然而,目前子痫前期的发病机制尚未明确,普遍认为子痫前期的发病与胎盘滋养细胞侵袭不足导致子宫-胎盘血管重塑异常及母体系统性炎症反应激活有关。已有大量的研究表明胎盘缺血和缺氧、氧化应激、血管生成与功能失衡、免疫失调、炎症反应、母体心血管功能障碍是子痫前期发病机制的重要组成部分。综述上述方面在子痫前期发病机制中的研究进展,以期从多个方面了解子痫前期的发生、发展,有助于子痫前期的早期诊断和干预,改善母婴结局。     

肥胖影响子宫内膜蜕膜化机制的研究进展

子宫内膜蜕膜化是胚胎植入、胎盘形成以及维持妊娠的必要条件,蜕膜化受损与多种不良妊娠结局有关。目前肥胖人群显著增多,对健康有不同程度的损害,肥胖女性子宫内膜间质细胞中蜕膜化标志物催乳素和胰岛素样生长因子结合蛋白1的mRNA表达明显降低,且肥胖对蜕膜化过程中涉及的孕激素相关蛋白、胰岛素受体底物2、信号转导与转录激活因子3、Wnt蛋白等相关因子及蜕膜免疫细胞均有影响,认为肥胖与蜕膜化受损具有密切的关系。研究肥胖与子宫内膜蜕膜化受损的相关性,有助于进一步了解子宫内膜蜕膜化受损的发病机制,对预防蜕膜化受损、改善不良妊娠结局具有重要意义。深入开展此方面的研究可能为肥胖型反复妊娠丢失患者的诊治提供新思路。     

Effect of relaxin on the decidual cell reaction in the Mongolian gerbil (Meriones unguiculatus)

Purpose  

Differentiation of endometrial stromal cells into decidual cells occurs during embryo implantation and pregnancy. Recently, it has been reported that relaxin affects the decidualization of cultured human endometrial cells in vitro; however, there has been no study on the decidualization of the Mongolian gerbil (Meriones unguiculatus). The authors demonstrated artificially induced decidualization, and the effect of relaxin on decidualization in gerbils.     

上皮-间质转化和蜕膜化与子宫内膜容受性

人类生殖过程涉及各种复杂因素,其中胚胎能否着床是受孕过程中的关键步骤。顺利的着床需要有正常生命力的胚胎在适当的时间植入具有接受性的子宫内膜,且胚胎与内膜达到同步交流状态。着床过程中任何一个环节出现差错都会影响妊娠率,而子宫内膜容受性下降可能是导致不孕的主要原因之一。着床初期子宫内膜上皮细胞发生上皮-间质转化（epithelial-mesenchymal transition,EMT）为后续胚胎的植入做准备,随后子宫内膜间质细胞发生蜕膜化为胚胎提供良好的发育环境。这提示EMT与蜕膜化是维持子宫内膜容受状态的基本条件,而良好的子宫内膜容受性是胚胎植入并充分发育的生物学基础。     

Interleukin-11 enhances cell survival of decidualized normal human endometrial stromal cells

High expression of interleukin-11 (IL-11) and the IL-11 receptor alpha chain in developing decidual cells in mice has been reported ,and mice lacking IL-11 receptor expression have been reported to show impaired implantation owing to defective decidualization. However ,the direct effect of IL-11 on endometrial stromal cells has not been studied. In this study ,we examined the direct effects of IL-11 on normal human endometrial stromal cells using an in vitro decidualization assay system. IL-11 enhanced cell viability and prolactin secretion of 8-Br-cAMP-induced decidualized cells but not of nonstimulated stromal cells. IL-11 dose-dependently enhanced the viability of stromal cells co-stimulated with 8-Br-cAMP and IL-11 without any significant effect on prolactin secretion from the cells. The extracellular matrix did not affect the effect of IL-11 on the viability of 8-Br-cAMP-stimulated stromal cells. These results indicate that IL-11 enhances the viability of 8-Br-cAMP-stimulated stromal cells and of decidualized stromal cells ,and that the cell survival signals generated by IL-11 are independent of those generated by the extracellular matrix. IL-11 produced locally in decidual tissues may enhance the viability of decidualized stromal cells and possibly protect against cell damage during embryo implantation and trophoblastic invasion.     

Interleukin-11 enhances cell survival of decidualized normal human endometrial stromal cells.

High expression of interleukin-11 (IL-11) and the IL-11 receptor alpha chain in developing decidual cells in mice has been reported, and mice lacking IL-11 receptor expression have been reported to show impaired implantation owing to defective decidualization. However, the direct effect of IL-11 on endometrial stromal cells has not been studied. In this study, we examined the direct effects of IL-11 on normal human endometrial stromal cells using an in vitro decidualization assay system. IL-11 enhanced cell viability and prolactin secretion of 8-Br-cAMP-induced decidualized cells but not of non-stimulated stromal cells. IL-11 dose-dependently enhanced the viability of stromal cells co-stimulated with 8-Br-cAMP and IL-11 without any significant effect on prolactin secretion from the cells. The extracellular matrix did not affect the effect of IL-11 on the viability of 8-Br-cAMP-stimulated stromal cells. These results indicate that IL-11 enhances the viability of 8-Br-cAMP-stimulated stromal cells and of decidualized stromal cells, and that the cell survival signals generated by IL-11 are independent of those generated by the extracellular matrix. IL-11 produced locally in decidual tissues may enhance the viability of decidualized stromal cells and possibly protect against cell damage during embryo implantation and trophoblastic invasion.     

Human endometrial decidual cell-associated 11 beta-hydroxysteroid dehydrogenase expression: its potential role in implantation

During pregnancy excess corticosteroid exposure can disturb the normal pattern of growth and differentiation of the primate fetus. This is normally prevented by the action of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which converts cortisol to its biologically inactive 11-oxo form, thereby ensuring that little or no cortisol is transferred to the fetus. During implantation, extravillous trophoblasts breech uterine vessels that are embedded in a decidual cell matrix. Through this invasive process the embryo gains requisite access to the maternal blood supply, while risking exposure to high circulating glucocorticoid levels. Thus, the expression of 11 beta-HSD by the decidual cell layer may be essential in regulating cortisol exposure of the developing embryo prior to placentation. In order to investigate the potential contribution of decidual cells to glucocorticoid metabolism, we evaluated the expression of both known 11 beta-HSD isoforms, 11 beta-HSD1, whose catalytic activity is NADP(+)-dependent, and NAD(+)-dependent 11 beta-HSD2, during decidualization of monolayers of human endometrial stromal cells. The differential actions of ovarian steroids on human endometrium are simulated in this in vitro model. Thus, progestins induce the expression of several decidualization markers in the cultured stromal cells, and consistent with its priming action in vivo, estradiol augments this expression. The results of our studies established a link between in vitro decidualization and enhanced glucocorticoid metabolizing capacity. Accordingly, the catalytic activities of both 11 beta-HSD isoforms were enhanced by incubation of the precursor stromal cells with medroxyprogesterone acetate, and further enhanced by estradiol, despite a lack of response to estradiol alone. This differential response to estradiol and progestin was reflected in parallel changes in steady state levels of 11 beta-HSD1 messenger RNA. The role of glucocorticoid metabolizing activity of the decidual cell is discussed in terms of its implications in determining the exposure of the implanting embryo to biologically active glucocorticoids.