分娩发动前后胎盘中白细胞抗原G1 mRNA和NK细胞的变化

目的:检测胎盘及蜕膜组织中白细胞抗原G1(HLA-G1)mRNA和NK细胞在足月妊娠分娩发动前后的变化,探讨其在分娩发动中的作用。方法:通过RT-PCR法检测足月妊娠晚期未临产组(剖宫产组)和临产组胎盘组织中HLA-G1 mRNA的表达,并用免疫组织化学方法测定蜕膜中NK细胞的数量。结果:与未临产组相比临产组胎盘组织中HLA-G1 mRNA表达明显下降,差异有统计学意义(P<0.05);临产组蜕膜中NK细胞数量明显多于未临产组(P<0.05)。结论:分娩发动时胎盘组织表达HLA-G1mRNA下降,蜕膜组织中NK细胞数量明显增多,推测HLA-G1表达下降激活NK细胞可能参与了分娩发动。     

Urocortin与妊娠

Urocortin是新近在哺乳动物中发现的促肾上腺皮质激素释放激素肽类家族的一员,人类胎盘及其他妊娠附属物均可合成.其具有引起垂体及胎盘局部促肾上腺皮质激素的分泌,扩张胎盘局部血管,增强子宫肌收缩力,增加胎盘局部前列腺素释放及抑制热损伤引起的水肿等作用.综述Urocortin与妊娠相关的内容.     

Uroconin与妊娠

Urocortin是新近在哺乳动物中发现的促肾上腺皮质激素释放激素肽类家族的一员，人类胎盘及其他妊娠附属物均可合成。其具有引起垂体及胎盘局部促肾上腺皮质激素的分泌，扩张胎盘局部血管，增强子宫肌收缩力，增加胎盘局部前列腺素释放及抑制热损伤引起的水肿等作用。综述Urocortin与妊娠相关的内容。     

妊娠期肝内胆汁淤积症患者血浆促肾上腺皮质激素释放激素增长受限

妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)是妊娠特有的并发症,其严重危害是突然胎死官内,具体机制尚未明了,可能是急性缺氧的结果,与子宫-胎盘-胎儿单位功能[1]及其血流调节[2]有关.胎盘小叶血管无神经分布,子宫-胎盘-胎儿单位血管床血流调控依赖于局部产生和循环中的血管舒张因子[3].促肾上腺皮质激素释放激素( corticotropin-releasing hormone,CRH)是近年研究较多的血管活性物质[4],主要由胎盘组织分泌,是妊娠期特殊标志物,对子宫-胎盘-胎儿单位血管具有强效的浓度依赖性舒张作用[5].关于CRH与ICP的关系尚未检索到相关文献报道,本研究通过测定ICP患者及正常妊娠孕妇血浆中CRH水平,观察ICP患者血浆CRH变化规律,探讨CRH与ICP胎儿缺氧的关系.     

母胎界面免疫微环境的研究进展

母胎界面是母体组织与胎儿成分直接接触的界面,其局部的免疫应答在妊娠的建立、维持以及临产的发动中均发挥关键作用.母胎界面免疫微环境由蜕膜中的免疫细胞及其分泌的细胞因子组成,在妊娠期类固醇激素等因素的影响下,蜕膜组织中淋巴细胞的亚群及其分泌的细胞因子均发生一系列的生理变化,构成母胎界面局部独特的、动态的免疫微环境.综述近年有关妊娠母胎界面的免疫微环境的研究进展.     

母胎界面免疫微环境的研究进展

母胎界面是母体组织与胎儿成分直接接触的界面，其局部的免疫应答在妊娠的建立、维持以及临产的发动中均发挥关键作用。母胎界面免疫微环境由蜕膜中的免疫细胞及其分泌的细胞因子组成，在妊娠期类固醇激素等因素的影响下，蜕膜组织中淋巴细胞的亚群及其分泌的细胞因子均发生一系列的生理变化．构成母胎界面局部独特的、动态的免疫微环境。综述近年有关妊娠母胎界面的免疫微环境的研究进展。     

子宫自然杀伤细胞与妊娠关系的研究进展

自然杀伤细胞(NK cell)是先天性免疫系统的重要组成部分。NK细胞在正常未孕子宫内膜存在,妊娠时显著增加,孕中期逐渐减少。NK细胞是妊娠母体子宫蜕膜最主要的免疫功能细胞,分泌多种细胞因子,在母胎界面免疫调控中起着重要的作用,并参与滋养细胞侵袭、血管重塑及早期胎盘形成等调节。子宫自然杀伤(uNK)细胞数量或功能失调可能打破母-胎界面细胞因子的平衡,使其内分泌紊乱,激活免疫细胞,杀伤胚胎,引发流产、子痫前期、胎儿生长受限等。本文就此方面的研究进展做一简要综述。     

雌激素受体信号通路与子痫前期的关系

子痫前期（pre-eclampsia,PE）是一种以高血压和多系统器官功能受累为特征的妊娠特异性综合征,虽然其具体发病机制尚不明确,但胎盘形成时期滋养细胞侵袭过浅或受限而导致的胎盘灌注不足、持续缺氧可能是重要的初始事件。作为胎盘分泌的重要类固醇激素,雌激素通过雌激素受体（estrogen receptor,ER）、雌激素反应元件（estrogen response element,ERE）信号通路的基因组或非基因组效应调控靶基因表达水平,致使滋养细胞增殖、凋亡和侵袭等生物学行为发生改变,还可能介导子宫内膜蜕膜化缺失从而参与胎盘浅着床、灌注不足的发生。雌激素及其信号通路还可通过调节一氧化氮等血管活性因子水平及有关离子通道活性,调节子宫动脉平滑肌的舒缩能力,通过多种机制参与PE、复发性流产等高危妊娠的发生和发展。     

青蒿琥酯抑制蜕膜-胎盘组织新生血管生成

目的:探讨青蒿琥酯终止妊娠的机制。方法:采用RIA测定妊娠大鼠血清孕酮(P),雌二醇(E2)和肿瘤坏死因子(TNF)水平;HE染色法观察大鼠蜕膜-胎盘及卵巢的组织病理学变化,免疫组化法Ⅷ因子单克隆抗体特异性血管内皮细胞染色标记计数蜕膜-胎盘组织的微血管(MVC),血管内皮生长因子(VEGF)单克隆抗体观察胚胎和骨髓的VEGF表达;脱氧核糖核酸末端转移酶介导dUTP缺口末端标记(TUNEL)检测孕体细胞凋亡。结果:青蒿琥酯40mg/kg×5d可使妊娠大鼠血清P水平显著下降(P<0.05),E2有下降趋势,TNF则有上升趋势;MVC密度显著下降(P<0.01),蜕膜-胎盘组织和骨髓的VEGF表达显著下调(P<0.01)。由此推断,青蒿琥酯能通过下调孕体-蜕膜-胎盘复合体的微血管生成和VEGF表达,造成蜕膜-胎盘组织受损,影响蜕膜-胎盘分泌激素的功能而导致血中孕酮水平迅速下降,黄体退化和靠孕激素支持的子宫内膜进一步脱落,最后使发育中的胚胎失去血液供应和营养,胚胎发育受阻,孕体被吸收。结论:青蒿琥酯通过抑制蜕膜-胎盘组织的新生血管生成,终止妊娠。     

分娩机制中细胞间隙连接蛋白CX43瞬时表达定位、定量分析及其意义(激光扫描共聚焦显微镜研究)

目的：探讨细胞间隙连接蛋白CX43在临产前后子宫平滑肌组织中的瞬时表达及其在分娩机制中的重要作用。方法：应用间接免疫荧光染色,结合激光扫描共聚焦显微镜技术,对19例足月妊娠未临产孕妇和23例临产孕妇,剖宫产子宫下段平滑脱组织中CX43蛋白表达的进行定位和定量分析。结果;未临产子宫平滑肌细胞胞质中CX43蛋白染色较弱,临产子宫平滑肌细胞CX43蛋白表达呈现强阳性信号。定量分析CX43在临产与未临产子宫中滑肌细胞中平均荧光强度分别为100像素线以上、100像素线以下;CX43蛋白表达阳性率分别为82．6％和36．8％,二者表达阳性率比较差并存在显著性（P＜0．05）。细胞间隙连接蛋白CX43在临产子宫平滑肌细胞中的时时高表达可能是宫缩过程中重要的事件,时阐明复杂的分娩机制提供了新的理论依据。     

Localization and characterization of urocortin during human pregnancy

Urocortin, a recently identified peptide of the corticotropin releasing hormone (CRH) peptide family, has potent vasodilatory effects in the human fetal placental circulation in vitro, promoting us to hypothesize that urocortin is produced locally to regulate uteroplacental vascular tone during pregnancy. In the present study, we examined the distribution of urocortin in the human placenta, fetal membranes and uterine tissue at term in the presence and absence of labour, using a urocortin antibody produced in our laboratory and the immunoperoxidase staining method. Immunoreactive (IR)-urocortin was observed in the vascular smooth muscle of the myometrium (n=5), decidual stromal cells, syncytiotrophoblast and amnion epithelium (n=10). No differences in staining intensity for urocortin were detected between tissues obtained in the absence (n=5) or presence (n=5) of labour. Staining intensity for IR-urocortin was greatest in the decidua suggesting this may be a site of urocortin production during pregnancy. Subsequently, we tested urocortin secretion from chorio-decidual cells in vitro, using an immunoblot technique. Positive staining for urocortin was observed in 40 per cent of chorio-decidual cells with 34 per cent of these cells secreting urocortin under basal conditions. Since urocortin was secreted by decidual cells we questioned whether urocortin was present in maternal plasma throughout gestation, using radioimmunoassay. Urocortin was detectable in maternal plasma from 7 weeks of gestation and concentrations did not change as gestation progressed. IR-urocortin in the maternal plasma eluted from a Sephadex G-50 column at the same site as synthetic urocortin and had a calculated retention coefficient (Kd) of 0.44. In summary, this study indicates that urocortin is produced by the decidua during human pregnancy and is detectable in maternal plasma. These data are consistent with the hypothesis that urocortin is produced locally by the decidua and may act to regulate uteroplacental blood flow.     

Immunohistochemical studies on collagen types in the uterine cervix in pregnant and nonpregnant states

The distribution of collagen types in pregnant and nonpregnant uterine cervices was examined by immunoperoxidase staining with the use of type-specific anticollagen antibodies. The nonpregnant cervix, composed of dense fibrous tissues, was diffusely stained with antibodies to type I and type III collagens. Type IV collagen was located only in the basement membrane region. In the cervix at term pregnancy, a marked decrease in fibrous connective tissue with increased proportions of smooth muscle fibers was characteristic, forming expanded spaces in between due to edema (clear spaces) with focal infiltrations of polymorphonuclear leukocytes. Type I and type III collagens were distributed only around smooth muscle fiber bundles with some fibroblasts attached. Type IV collagen was distributed in a linear fashion delineating individual smooth muscle fibers and vascular basement membranes. A possible role of infiltrated polymorphonuclear leukocytes in the dissociation of fibrous connective tissues of the cervix at term pregnancy is discussed.     

Activin betaA-subunit and activin receptors in human myometrium at term and during labour

Objective To measure activin A content and to localise and semi-quantitate activin receptors in human myometrium at term and during labour.
Design Myometrium was collected from non-pregnant women (   n = 6  ), pregnant women at term not in labour (   n = 6  ) and at term in labour (   n = 6  ).
Setting Monash Medical Centre, Melbourne, Australia.
Main outcome measures Tissue lysates of myometrium were analysed for activin A content using an enzyme-linked immunosorbent assay and activin receptor proteins IA, IIA and IIB using Western hybridisation. Activin β_A-subunit and activin receptors were localised in myometrium by immunohistochemistry.
Results Activin A was detected by ELISA in non-pregnant, pregnant and labouring myometrium. Levels were significantly higher in labouring myometrium. The three activin receptors IA, IIA and IIB were detected in all myometrial samples by Western hybridisation. Receptor IA was expressed in significantly higher levels in pregnant myometrium. Receptor IIA was very weakly expressed throughout. The expression of receptor IIB was similar in all three groups. Activin β_A-subunit and all three receptors were localised to the endothelial cells of myometrial blood vessels. Neither activin β_A-subunit nor any of the three activin receptors were immunolocalised to myometrial smooth muscle cells in the three groups. This result was confirmed by Western blotting for expression of activin receptors in isolated myometrial smooth muscle and microvascular endothelial cells.
Conclusion The myometrium is not a target for activin A during late pregnancy or labour. However, activin A may have a role in the regulation of microvascular endothelial cell function in the myometrium.     

Uterine artery Doppler in predicting pregnancy outcome in women with antiphospholipid syndrome

OBJECTIVE: To determine the expression and localization of cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), E-selectin, platelet-endothelial cell adhesion molecule (PECAM), and vascular cell adhesion molecule (VCAM) in the cervix and myometrium during pregnancy and labor. METHODS: Biopsies of myometrium and cervix were obtained from non-pregnant women and from pregnant women before and after onset of spontaneous labor at term. Cell adhesion molecule mRNA expression was quantified using Northern blotting and cell adhesion molecule protein was localized using immunohistochemistry. RESULTS: ICAM-1 mRNA was upregulated in the cervix (10-fold increase, P <.01) and myometrium (10.5-fold increase, P <.01) during labor. ICAM-1 was localized in the vascular endothelium and in leukocytes in the cervix and myometrium from all three groups of women. VCAM mRNA was upregulated in the cervix (2.5-fold increase, P <.01) during pregnancy and there was no further change during labor. VCAM localized weakly to the vascular endothelium in cervical and myometrial biopsies from pregnant and non-pregnant women. PECAM mRNA was significantly upregulated in myometrium during pregnancy (ninefold increase, P <.01) and did not change with the onset of labor. PECAM localized to the vascular endothelium in all cervical and myometrial biopsies and was identified on leukocytes. There were no significant changes in E-selectin mRNA expression in either tissue with pregnancy or parturition. CONCLUSION: Cell adhesion molecule expression changes in human cervix and myometrium during pregnancy and parturition. At least part of these changes are attributable to expression by leukocytes infiltrating these tissues.     

Preeclampsia and Calcium‐ATPase Activity of Plasma Membranes from Human Myometrium and Placental Trophoblast

Objective: We determined calcium‐activated adenosine triphosphatase (Ca‐ATPase) activity and thiobarbituric acid‐reactive substances (TBARS) of plasma membranes from myometrium and placental trophoblast of normotensive and preeclamptic pregnant women. Methods: Samples of myometrium were obtained by uterine biopsies taken upon delivery by cesarean section from nulliparous normotensive and preeclamptic pregnant women. Placentas were obtained after full term vaginal delivery from either normotensive or preeclamptic women. Plasma membrane fractions were prepared from both myometrium and placenta and assayed for Ca‐ATPase activity and TBARS. Main Outcome Measure(s): We expected to find a higher level of TBARS and, consequently, a lower activity of Ca‐ATPase of the plasma membrane fractions obtained from both myometrium and placenta of preeclamptic women. Results: The Ca‐ATPase activity of myometrium and placental trophoblast from preeclamptic women was about 50% lower than that from normotensive women, while the TBARS were higher. Conclusions: A reduced Ca‐ATPase activity, caused by an increased level of TBARS, may result in an increase in the cytosolic calcium concentration in the vascular smooth muscle cells of preeclamptic women and thus partially explain the high blood pressure developed by these patients.     

Levels of maternal plasma corticotropin-releasing factor and urocortin during labor

OBJECTIVE: Corticotropin-releasing factor (CRF) is produced by the placenta and intrauterine tissues and secreted in increasing amounts from early to term pregnancy. In the presence of labor, a more incisive increase in CRF levels has been described, and women with preterm labor or those destined to have premature delivery have higher midpregnancy CRF levels than those who deliver at term. Urocortin is a 40-amino acid peptide belonging to the CRF family, expressed by human trophoblast and fetal membranes, which has the same biologic effects as CRF. Acting on the same CRF receptors, urocortin stimulates myometrial contractility and ACTH and prostaglandin release from cultured human placental cells. Because no data exist about urocortin levels in the maternal circulation at parturition, we investigated whether maternal plasma urocortin and CRF levels change according to cervical dilatation in healthy pregnant women at term labor.METHODS: In a cross-sectional study of labor, a single maternal blood sample was collected from healthy pregnant women at term (n = 40); in a second longitudinal study, plasma samples were collected longitudinally in a subset of patients (n = 8) throughout labor, according to a Bishop score evaluation.RESULTS: Both maternal plasma CRF and urocortin levels were higher in labor than those previously reported during pregnancy, but they did not change significantly during the different stages of labor when evaluated longitudinally. Some patients showed a trend toward increasing levels, whereas others had variable concentrations.CONCLUSION: Neither CRF nor urocortin levels changed during the progression of spontaneous labor.     

Activin βA-subunit and activin receptors in human myometrium at term and during labour

Objective To measure activin A content and to localise and semi-quantitate activin receptors in human myometrium at term and during labour.Design Myometrium was collected from non-pregnant women (n = 6), pregnant women at term not in labour (n = 6) and at term in labour (n = 6).Setting Monash Medical Centre, Melbourne, Australia.Main outcome measures Tissue lysates of myometrium were analysed for activin A content using an enzyme-linked immunosorbent assay and activin receptor proteins IA, IIA and IIB using Western hybridisation. Activin β_A-subunit and activin receptors were localised in myometrium by immunohistochemistry.Results Activin A was detected by ELISA in non-pregnant, pregnant and labouring myometrium. Levels were significantly higher in labouring myometrium. The three activin receptors IA, IIA and IIB were detected in all myometrial samples by Western hybridisation. Receptor IA was expressed in significantly higher levels in pregnant myometrium. Receptor IIA was very weakly expressed throughout. The expression of receptor IIB was similar in all three groups. Activin β_A-subunit and all three receptors were localised to the endothelial cells of myometrial blood vessels. Neither activin β_A-subunit nor any of the three activin receptors were immunolocalised to myometrial smooth muscle cells in the three groups. This result was confirmed by Western blotting for expression of activin receptors in isolated myometrial smooth muscle and microvascular endothelial cells.Conclusion The myometrium is not a target for activin A during late pregnancy or labour. However, activin A may have a role in the regulation of microvascular endothelial cell function in the myometrium.     

Progesterone receptor localization and isoforms in myometrium,decidua, and fetal membranes from rhesus macaques: evidence for functional progesterone withdrawal at parturition

OBJECTIVE: It is not known whether withdrawal of progesterone (P) action is a prerequisite for parturition in women or in nonhuman primates because concentrations of circulating progesterone or progesterone receptors (PR) in myometrium and decidua do not decrease before delivery. To examine this potentially important regulatory mechanism, we determined PR isoforms, PR localization, and mRNA in myometrium, decidua, and fetal membranes from rhesus monkeys during pregnancy and in spontaneous labor at term.METHODS: Gestational tissues were obtained midpregnancy (day 80-100), late pregnancy (day 130-145), and during spontaneous labor at term (day 161-167). Samples of rhesus monkey myometrium, decidua, chorion-decidua, and amnion were collected and analyzed for total nuclear and cytosolic PR by competitive binding assay. Progesterone receptor isoforms were identified and quantified by Western blot analysis, and PR mRNA was determined by a specific ribonuclease protection assay. Nuclear PR was localized by immunohistochemistry with monoclonal anti-PR (JZB39) after microwave stabilization.RESULTS: Myometrium and decidua showed no change in total PR during pregnancy and labor. Nuclear PR was not detected in fetal membranes by binding assay but was localized in amnion epithelial and mesenchymal cells and in chorion laeve cytotrophoblasts by immunohistochemistry. Staining for PR was substantially less by serial antibody dilution in fetal membranes than in decidua. Message for PR was confirmed in all tissues analyzed. A significant (P <.05) shift in the ratio of PR isoforms (from PR-B dominance at midpregnancy to PR-A dominance in labor) was observed in myometrium but not in decidua. Both PR-A and PR-B isoforms and PR nuclear staining were nearly undetectable in amnion obtained during labor.CONCLUSION: A shift to PR-A dominance in myometrium at term together with a loss of PR in fetal membranes provides evidence for a functional progesterone withdrawal mechanism, which may facilitate the initiation of parturition in primates.     

Hydrogen sulfide inhibits the spontaneous and oxytocin-induced contractility of human pregnant myometrium

Hydrogen sulfide (H₂S) is a novel endogenous gaseous signaling transmitter in mammalian tissues including smooth muscle tissues. We investigated the effect of sodium hydrosulfide (NaHS), a H₂S donor, on the contractility of isolated human myometrium strips from term pregnant women who were undergoing labor. Cumulative effects of NaHS on spontaneous and oxytocin-induced contractility were evaluated by using isometric tension recordings. NaHS (0.1?μM–1 mM) concentration dependently inhibited spontaneous contractility of laboring myometrium, with a decrease in amplitude and frequency. NaHS (0.1?μM–1 mM) decreased the frequency but not the amplitude of oxytocin (1?μM)-induced contractions. NaHS-induced relaxation could be prevented by pretreatment with glibenclamide, an inhibitor of K⁺_ATP channels. Thus, NaHS evokes relaxation of human pregnant myometrium, suggesting a possible role of H₂S during human pregnancy.