妊娠高血压综合征胎盘滋养细胞中胰岛素样生长因子Ⅱ及其mRNA的表达

目的　检测胎盘滋养细胞中胰岛素样生长因子Ⅱ (insulin likegrowthfactorⅡ ,IGF Ⅱ )及其mRNA的表达 ,评估IGF Ⅱ在妊娠高血压综合征 (妊高征 )发病中的作用。　方法　 (1)用免疫组化法检测正常及妊高征孕妇胎盘组织中IGF Ⅱ的表达 ,并用计算机图像分析系统进行定量分析比较。 (2 )用逆转录 聚合酶链反应 (RT PCR)检测正常妊娠及妊高征胎盘滋养细胞IGF ⅡmRNA表达水平 ,并通过紫外凝胶图像分析进行定量分析比较。　结果　 (1)IGF Ⅱ主要位于绒毛小叶的合体滋养细胞及细胞滋养细胞。此外 ,也存在于羊膜绒毛层 ,但染色较以上两种细胞明显减弱。(2 )与正常妊娠胎盘组 (0 36 0± 0 0 72 )比较 ,妊高征组IGF Ⅱ的平均光密度 (0 32 4± 0 0 4 2 )显著降低 (P <0 .0 5 )。 (3)妊高征胎盘滋养细胞IGF ⅡmRNA的表达 (0 72± 0 72 )亦显著低于正常妊娠者(0 96± 0 30 ,P <0 .0 5 )。　结论　胎盘滋养细胞表达IGF Ⅱ减少可能与妊高征的发病有关。     

妊娠高血压综合征患者胎盘整合素α1、β1的表达与细胞凋亡

目的　通过观察妊娠高血压综合征 (妊高征 )患者胎盘整合素α1、β1的表达 ,探讨整合素在细胞凋亡中的作用及二者对妊娠结局的影响 ;了解不同程度及不同民族妊高征胎盘α1、β1的表达情况。 　方法　采用免疫组织化学法测定 40例妊高征患者胎盘组织中的整合素α1、β1,以 43例正常妊娠晚期妇女胎盘组织作对照 ;采用DNA缺口原位标记Tunel技术 ,测定 12例妊高征患者胎盘不同细胞凋亡指数 ,以 2 4例正常妊娠妇女胎盘作对照。　结果　 (1)妊高征组胎盘细胞滋养细胞、合体滋养细胞、蜕膜细胞凋亡指数分别为 (11.0 4± 3 .46) %、(12 .2 0± 3 .67) %、(13 .0 3± 4.3 8) % ,明显高于对照组的 (3 .91± 1.65 ) %、(5 .3 9±1.76) %、(4 .0 8± 1.97) % ,差异均有显著性 (P <0 .0 5 ) ;(2 )妊高征组整合素α1、β1在胎盘组织中的表达均低于对照组 ,差异有显著性 (α1:T =14 42 ,P <0 .0 5 ;β1:T =12 47,P <0 .0 1) ;(3 )中度与重度妊高征患者胎盘整合素α1的表达也有差异 (T =5 6,P <0 .0 1) ,而整合素 β1的表达无明显统计学差异 ;(4 )汉族与维吾尔族之间胎盘整合素α1的表达无明显统计学差异。　结论　 (1)妊高征的不良妊娠结局与细胞凋亡有密切关系。 (2 )整合素α1、β1的低表达是胎盘细胞凋亡的重要因素     

重度妊娠高血压综合征患者胎盘组织细胞凋亡及其调控基因 …

目的　研究细胞凋亡及其调控基因在重度妊娠高血压综合征 (妊高征 )发生、发展中的作用。方法　对 40例正常晚孕妇女 (对照组 )和 40例重度妊高征患者 (观察组 )的胎盘组织进行分析。用DNA缺口原位末端标记 (TUNEL)技术检测细胞凋亡 ;免疫组织化学方法检测促进和抑制凋亡基因 (bax/bcl 2 )的表达。结果　对照组胎盘细胞滋养细胞、合体滋养细胞中凋亡指数分别为 ( 1.1±0 .9) %、( 41.8± 1.5 ) % ;bax阳性率分别为 ( 1.0± 0 .9) %、( 2 8.9± 9.7) % ;bcl 2阳性率分别为 ( 2 .2±0 .8) %、( 2 2 .9± 0 .7) % ,总bax/bcl 2为 0 .7～ 1.7。观察组胎盘细胞滋养细胞、合体滋养细胞的凋亡指数分别为 ( 4.3± 1.2 ) %、( 45 .3± 1.4) % ;bax阳性率分别是 ( 2 .2± 0 .8) %、( 42 .5± 11.7) % ;bcl 2阳性率分别是 ( 3 .2± 0 .8) %、( 2 3 .3± 7.8) % ;总bax/bcl 2为 1.0～ 3.2。即 :对照组胎盘中有一定量的细胞凋亡、bax、bcl 2表达 ,bax/bcl 2表达间呈平衡趋势 ;观察组中细胞凋亡明显增高 (P <0 .0 1) ,bax表达也明显增强 (P <0 .0 1) ,bcl 2表达仅呈增高趋势 ,但差异无显著性 (P >0 .0 5 ) ,bax/bcl 2比值明显增高(P <0 .0 1)。结论　细胞凋亡及其调节基因的表达间具有一致性 ;细胞凋亡、bax/bcl 2表达     

妊高征患者胎盘滋养细胞中转化生长因子β1的表达及意义

目的 :探讨胎盘组织中转化生长因子 β1 (TGF β1 )的定位 ,检测滋养细胞中TGF β1mRNA的表达水平 ,评估TGF β1在妊娠高血压综合征 (妊高征 )中的作用。方法 :用免疫组化法对 30例正常孕妇、2 5例妊高征孕妇的胎盘组织进行TGF β1定位 ;用逆转录 聚合酶链反应 (RT PCR)检测正常妊娠滋养细胞 6例、妊高征滋养细胞 6例中TGF β1mRNA表达水平 ,并进行定量分析。结果 :(1 )胎盘TGF β1主要位于绒毛小叶的合体滋养细胞及细胞滋养细胞 ;(2 )与正常组比较 ,妊高征组胎盘TGF β1的平均光密度显著增加(P <0 .0 5) ;(3)与正常滋养细胞比较 ,妊高征滋养细胞TGF β1mRNA的表达强度显著增强(P <0 .0 5)。结论 :胎盘组织中TGF β1主要位于胎盘小叶的合体滋养细胞、细胞滋养细胞 ,胎盘滋养细胞合成TGF β1的增多与妊高征的发生有关     

胎盘滋养细胞表面FasL的表达异常与妊娠高血压综合征的关系

目的　通过比较正常孕妇与妊娠高血压综合征 (简称妊高征 )患者胎盘滋养细胞表面Fas L(Fas配体 )表达 ,进一步从分子免疫学角度探讨妊高征的免疫病理机制。　方法　用特异性的Fas L 抗体对中、重度妊高征患者胎盘滋养细胞表面 Fas L 进行免疫组化染色 ,并通过高清晰彩色病理免疫组化测量系统对其定量分析 ,与同孕周的正常孕妇进行比较。　结果　妊高征组胎盘滋养细胞表面 Fas L 表达面积 [(6 9.6 2 8± 19.10 3) μm2 ]明显低于正常组 [(97.46 1± 10 .5 17) μm2 ],两者间差异有非常显著意义 (P<0 .0 1)。妊高征组胎盘滋养细胞表面 Fas L 表达强度 ,包括平均光度 (0 .117±0 .0 2 2 )及积分光度 (14.36 7± 3.15 6 )也明显低于正常组 (分别为 0 .145± 0 .0 15与 18.5 88± 3.897) ,两者间差异有非常显著意义 (P<0 .0 1)。　结论　胎盘滋养细胞表面 Fas L 表达减少 ,导致母胎间的免疫耐受的破坏 ,引起异常的免疫反应可能是妊高征发病的重要机制。诱导 Fas L 的产生或调节母胎间的免疫耐受 ,将为临床治疗妊高征提供新的方向。     

妊娠高血压综合征胎盘细胞凋亡现象及凋亡相关基因表达的研究

妊娠高血压综合征 (简称妊高征 )的病因和发病机理至今未完全阐明。国外学者认为细胞凋亡在胎盘发生、发育、老化过程中起重要作用 ,并介导许多病理妊娠的发生 [1 ]。本实验旨在研究妊高征患者胎盘细胞凋亡发生率以及凋亡相关基因在胎盘部位的表达 ,从而探讨细胞凋亡在妊高征发     

妊娠肝内胆汁淤积症患者胎盘细胞凋亡及调控基因的研究

目的　通过观察妊娠肝内胆汁淤积症 (ICP)患者胎盘细胞凋亡调控基因p5 3、bax和bcl 2在胎盘中的表达 ,探讨细胞凋亡基因在胎盘细胞凋亡中的作用。方法　采用原位末端标记法(TUNEL)和免疫组织化学方法对 3 1例ICP患者 (ICP组 )的胎盘组织中p5 3、bax和bcl 2基因表达及调亡指数进行检测 ,并以 3 1例正常妊娠妇女的胎盘组织作对照 (对照组 )。结果　 (1)ICP组胎盘组织中细胞滋养细胞、合体滋养细胞、蜕膜细胞及间质细胞中细胞凋亡指数分别为 (49 1± 9 1) %、(46 6±9 8) %、(3 5 1± 9 5 ) %、(3 8 7± 9 7) % ,明显高于对照组的 (2 2 5± 6 2 ) %、(2 1 6± 5 2 ) %、(17 9±6 2 ) %、(17 0± 4 7) %。两组比较 ,差异有极显著性 (P <0 0 1)。 (2 )而调控基因p5 3的表达 ,ICP组明显高于对照组 ,两组比较 ,差异有极显著性 (P <0 0 1) ;bax的表达在两组滋养细胞中比较 ,差异无显著性 (P >0 0 5 )。但在合体滋养细胞、蜕膜细胞及间质细胞中 ,ICP组明显高于对照组 ,两组比较 ,差异有极显著性 (P <0 0 1) ;bcl 2的表达在ICP组胎盘组织细胞滋养细胞、合体滋养细胞、蜕膜细胞及间质细胞中 ,均明显低于对照组 (P <0 0 1)。 (3 )p5 3、bax和bcl 2在ICP组合体滋养细胞中的表达分别是 (75 9± 8 2 ) %、(65     

妊娠高血压综合征患者胎盘还原型烟酰胺腺嘌呤二核苷酸脱氢酶基因的表达

目的　研究还原型烟酰胺腺嘌呤二核苷酸 (NADH)脱氢酶基因在妊娠高血压综合征 (妊高征 )患者胎盘组织中的表达 ,了解其在妊高征发病中的作用。方法　采用32 P标记的NADH脱氢酶cDNA探针斑点印迹杂交方法 ,对 10例正常妊娠妇女 (对照组 )及 10例中、重度妊高征患者 (妊高征组 )的胎盘组织总RNA进行检测 ,以图像处理系统测量每个杂交点的平均吸光度 (A)值 ,比较两组胎盘组织NADH脱氢酶mRNA水平。结果　妊高征组和对照组胎盘组织NADH脱氢酶平均A值分别为 2 1± 6、5 6± 16;妊高征组胎盘组织NADH脱氢酶mRNA的表达明显高于对照组 ,两组比较 ,差异有显著性 (P <0 0 5 )。结论　妊高征患者胎盘组织NADH脱氢酶基因表达的增加 ,可能在妊高征发病中起一定作用     

妊高征患者胎盘组织血管紧张素Ⅱ 1型受体和血管紧张素原的表达

目的　探讨血管紧张素Ⅱ 1型受体 (angiotensinⅡtype 1receptor ,AT1R)和血管紧张素原 (angiotensinogen ,AGT)在妊娠高血压综合征 (妊高征 )患者胎盘组织中表达的变化及其在妊高征发病中的意义。　方法　采用免疫组织化学染色法 (免疫组化 )和逆转录聚合酶链反应法 (RT PCR) ,检测 2 0例中、重度妊高征患者 (妊高征组 )和 15例正常妊娠妇女 (正常组 )的胎盘组织AT1R水平及AT1RmRNA和AGTmRNA的表达。　结果　 ( 1)AT1R主要定位于胎盘绒毛滋养细胞、血管内皮细胞及血管平滑肌细胞。 ( 2 )免疫组化定量灰度分析 ,妊高征组胎盘组织AT1R阳性表达( 112 .4 3± 11.75 )显著强于正常组 ( 170 .4 7± 10 .5 9) (P <0 .0 1)。 ( 3)妊高征组胎盘组织AT1RmRNA的表达水平 ( 0 .96± 0 .2 0 )高于正常组 ( 0 .5 6± 0 .14 ) (P <0 .0 1)。妊高征组胎盘组织AGTmRNA的表达水平 ( 1.0 8± 0 .2 2 )亦显著高于正常组 ( 0 .6 0± 0 .12 ) (P <0 .0 1)。　结论　在妊高征患者胎盘组织中 ,AT1R和AGT表达均有明显增加 ,说明胎盘组织局部肾素 血管紧张素系统与妊高征发病有相关性     

正常及妊娠高血压综合征孕妇胎盘组织中去甲肾上腺素和多巴胺的研究

目的　通过对正常孕妇及妊娠高血压综合征 (妊高征 )孕妇胎盘组织中去甲肾上腺素(NE)及多巴胺 (DA)的定位及定量测定 ,探讨其与妊高征发病的关系。方法　应用免疫组织化学 (免疫组化 )链霉素抗生物素 -过氧化物酶法 ,对 31例正常早、中、晚孕妇女 (正常孕妇组 ) ,及 38例轻、中、重度妊高征孕妇 (妊高征孕妇组 )的胎盘组织进行NE和DA定位 ;并应用电子计算机图像分析系统进行定量 ,其结果以灰度值倒数表示。结果　 (1)两组孕妇胎盘组织NE及DA免疫组化定位 :正常孕妇组中 ,早期孕妇的胚胎绒毛滋养细胞NE及DA免疫反应呈现强阳性 ,呈深棕色 ,定位于细胞滋养细胞的细胞膜及细胞浆中 ;中、晚期孕妇胎盘组织NE及DA免疫反应表现为阳性 ,呈棕色 ,或弱阳性呈浅棕色 ,定位于合体滋养细胞的细胞膜及细胞浆 ,以及毛细血管内皮。妊高征孕妇组的胎盘组织NE、DA定位与正常孕妇组中的晚期孕妇相同。 (2 )两组孕妇胎盘组织NE及DA免疫组化定量 (灰度倒数值 ) :正常孕妇组NE由孕早期的 1 5 95± 0 0 18降至中、晚期的 1 4 88± 0 0 19和 1 4 19± 0 0 14 (P<0 0 1) ;DA由孕早期的 1 5 5 2± 0 0 6 7,降至中、晚期的 1 36 9± 0 0 5 1和 1 30 2± 0 0 13(P <0 0 1)。妊高征孕妇组妊高征轻、中、重度的DA ,依次为 1 37     

Heparin and aspirin attenuate placental apoptosis in vitro: implications for early pregnancy failure

OBJECTIVE: Live birth rates are increased by treatment with heparin and aspirin in cases of poor pregnancy outcome such as antiphospholipid syndrome. Both drugs may attenuate miscarriage by inhibiting aberrant coagulation or by modulating trophoblast apoptosis. Here we assessed their roles in trophoblast apoptosis in vitro. STUDY DESIGN: BeWo cells and placental villi were cultured in sera from women with successful or failing in vitro fertilization, with and without heparin or aspirin. Apoptosis was assessed by using DNA laddering, cytokeratin 18 neoepitope formation, Bcl-2, and caspase 7 expression. RESULTS: In BeWo cells, sera from in vitro fertilization failure increased trophoblast apoptosis, whereas heparin and aspirin reversed these effects. In villous trophoblast, heparin increased Bcl-2 and cytokeratin 18 protein expression. Heparin and aspirin inhibited DNA laddering. CONCLUSION: Heparin and aspirin modulate trophoblast apoptosis suggesting a direct impact on trophoblast biology, thus providing an additional mechanism to explain the clinical benefits of heparin and aspirin on recurrent pregnancy loss.     

特发性胎儿生长受限与胎盘细胞凋亡及bcl-2基因表达的关系

目的 探讨特发性胎儿生长受限(FGR)与胎盘细胞凋亡及bcl-2基因表达的关系.方法 应用透射电镜、脱氧核苷酸末端转移酶介导的脱氧尿苷三磷酸标记法(TUNEL)、流式细胞技术(FCM)检测特发性FGR孕妇(FGR组)及正常妊娠妇女(对照组)各15例的胎盘细胞凋亡情况,并采用RT-PCR技术观察两组胎盘细胞中bcl-2基因相对表达量.结果 电镜下观察到FGR组胎盘合体滋养细胞核膜皱缩,核仁消失,染色质致密、凝聚;TUNEL 检测 FGR 组胎盘细胞凋亡率为13.68%,高于对照组的4.05%,两组比较,差异有统计学意义(P<0.05);FCM检测胎盘S期细胞比率FGR组为3.4%,对照组为2.2%,两组比较,差异有统计学意义(P<0.05),FCM检测的胎盘细胞凋亡率变化趋势与TUNEL检测结果一致;FGR组胎盘细胞bcl-2基因相对表达量为0.19±0.13,对照组为0.55±0.17,两组比较,差异也有统计学意义(P<0.05).结论 特发性FGR的发生与胎盘细胞凋亡增加有关,胎盘细胞凋亡增加与胎盘细胞中bcl-2基因表达下调有一定关系.     

血管内皮生长因子与妊娠高血压综合征发病及一氧化氮的关系

目的　探讨血管内皮生长因子（VEGF）在妊娠高血压综合征（妊高征）发病中的作用,及其与一氧化氮（NO）的关系。方法　选择妊高征患者(妊高征组)41例,其中轻度妊高征12例,中度妊高征13例,重度妊高征16例;选择同期正常晚期妊娠妇女20例为对照组。采用酶联免疫吸附法测定两组孕妇血清VEGF水平,用硝酸盐还原酶法测定两组胎盘组织NO浓度变化。结果　（1）妊高征组血清VEGF水平明显低于对照组,轻度妊高征患者血清VEGF水平与对照组比较,差异无显著性,中、重度妊高征患者血清VEGF水平分别为（23.1±4.1）ng/L、（14.8±3.9）ng/L,明显低于对照组。（2）妊高征组胎盘组织中NO浓度较对照组明显降低,轻度妊高征患者胎盘组织NO浓度与对照组比较,差异无显著性,中、重度妊高征患者胎盘组织NO浓度分别为（9.1±2.1）μmol/g、(5.6±1.8)μmol/g,均明显低于对照组。（3）血清VEGF水平与胎盘组织NO浓度呈显著正相关（r=0.65,P<0.01）。结论　妊高征患者血清中VEGF水平降低,胎盘组织中NO浓度下降,可能在妊高征的发病中起一定作用。     

Antenatal dexamethasone treatment leads to changes in gene expression in a murine late placenta

Antenatal steroids like dexamethasone (DEX) are used to augment fetal lung maturity and there is a major concern that they impair fetal growth. If delivery is delayed after using antenatal DEX, placental function and hence fetal growth may be compromised even further. To investigate the effects of DEX on placental function, we treated 9 pregnant C57/BL6 mice with DEX and 9 pregnant mice were injected with saline to serve as controls. Placental gene expression was studied using microarrays in 3 pairs and other 6 pairs were used to confirm microarray results by semi-quantitative RT-PCR, real-time PCR, in situ hybridization, western blot analysis and Oligo ApopTaq assay. DEX-treated placentas were hydropic, friable, pale, and weighed less (80.0+/-15.1mg compared to 85.6.8+/-7.6mg, p=0.05) (n=62 placentas). Fetal weight was significantly reduced after DEX use (940+/-32mg compared to 1162+/-79mg, p=0.001) (n=62 fetuses). There was >99% similarity within and between the three gene chip data sets. DEX led to down-regulation of 1212 genes and up-regulation of 1382 genes. RT-PCR studies showed that DEX caused a decrease in expression of genes involved in cell division such as cyclins A2, B1, D2, cdk 2, cdk 4 and M-phase protein kinase along with growth-promoting genes such as EGF-R, BMP4 and IGFBP3. Oligo ApopTaq assay and western blot studies showed that DEX-treatment increased apoptosis of trophoblast cells. DEX-treatment led to up-regulation of aquaporin 5 and tryptophan hydroxylase genes as confirmed by real-time PCR, and in situ hybridization studies. Thus antenatal DEX treatment led to a reduction in placental and fetal weight, and this effect was associated with a decreased expression of several growth-promoting genes and increased apoptosis of trophoblast cells.     

Placental Fas and Fas ligand expression in normal early, term and molar pregnancy

To clarify the Fas and Fas-ligand status of normal and molar trophoblast, the expression of Fas and FasL by placental trophoblast populations in partial and complete hydatidiform moles was compared with that in normal first trimester and term pregnancies using an avidin-biotin peroxidase technique on frozen and formalin-fixed paraffin-embedded placental tissues with both monoclonal and polyclonal antibodies. The TUNEL technique was used to detect apoptotic cells in the same tissues. The immunoreactivity for Fas and Fas-ligand was comparable with both monoclonal and polyclonal antibodies on frozen as well as paraffin-embedded sections. In normal early and molar pregnancy there was strong FasL expression by villous cytotrophoblast and syncytiotrophoblast. However, there were significant differences in FasL expression by trophoblast subpopulations in both early and term normal pregnancy and between the same trophoblast subpopulation at different gestations, with FasL staining generally being weaker at term. Strong FasL staining by cytotrophoblast cells in the distal parts of cell columns contrasted with unstained cytotrophoblast in the proximal part of columns. Distinct trophoblast subpopulations in partial hydatidiform mole also differentially expressed FasL with reduced FasL expression in proliferating syncytiotrophoblast. In contrast there was no differential FasL expression in complete hydatidiform mole, all trophoblast subpopulations strongly expressing FasL. Unlike the differential expression of FasL there were no differences in Fas expression by trophoblast populations in normal early or term placental tissues. Fas expression was reduced in villous cytotrophoblast at term. Differential expression of Fas by different trophoblast subpopulations was noted in partial and complete hydatidiform mole. In complete mole villous cytotrophoblast and syncytiotrophoblast stained strongly compared with proliferating trophoblast. Using TUNEL labelling apoptosis was rarely detected in placental trophoblast. Differential Fas and FasL expression by trophoblast subpopulations in normal and pathological pregnancy does not appear to be related to apoptosis of trophoblast.     

基因芯片研究妊娠高血压综合征患者胎盘组织基因表达的变化

目的 检测妊娠高血压综合征(妊高征)患者胎盘组织和正常妊娠胎盘组织差异表达基因谱。方法 Trizol法抽提组织总RNA并纯化mRNA；应用cDNA阵列人类全基因表达谱分析芯片检测6例妊高征患者胎盘组织和5例正常妊娠者胎盘组织中差异表达的基因，扫描仪分析结果。结果 所检测的17000个基因中，妊高征患者胎盘组织与正常妊娠者胎盘组织之间存在差异表达基因96个，表达上调基因数为78个，下调基因数为18个。初步分析发现，有85个已知功能基因，其中79个功能分类基因，大致分为癌基因和细胞周期蛋白、细胞骨架和运动蛋白、细胞分裂、离子通道和运输蛋白、细胞凋亡和应激反应蛋白、细胞受体、免疫、细胞信号和传递蛋白、转录和翻译系统、代谢、发育、细胞分化相关基因，另外有6个未分类基因、8个未知基因表达序列标签、3个cDNA片段。结论 妊高征发病的分子机制可能涉及了一些基因表达的变化。     

Correlation with placental kisspeptin in postterm pregnancy and apoptosis

Postterm pregnancy represents a condition associated with trophoblast apoptosis. Kisspeptin is a peptide able to induce apoptosis by a specific receptor, GPR54, through the upregulation of proapoptotic genes. The aims of the study were to evaluate (1) the messenger RNA (mRNA) expression of kisspeptin, GPR54, Bax/Bcl2, and p21 in postterm placentas and (2) kisspeptin ability to act on apoptosis in the third trimester placental explants. Placental specimens were collected from spontaneous term and postterm delivery and kisspeptin, GPR54, Bax/Bcl2, and p21 mRNA expression levels were analyzed by real-time polymerase chain reaction. Placental explants, collected from elective term cesarean sections, treated with different doses of kisspeptin were analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression levels of all the genes studied in postterm placentas were significantly higher than in-term placentas. Kisspeptin-induced apoptosis in placental explants with a dose-dependent effect, and TUNEL assay demonstrated the kisspeptin involvement in the apoptotic placental processes. Our present findings led us to hypothesize that kisspeptin may represent a placental proapoptotic agent acting in physiological and/or pathological pregnancy conditions in which placental apoptosis mechanisms are increased.     

Developmental Ability of Trophoblast Stem Cells in Uniparental Mouse Embryos

Neither parthenogenetic (PG) nor androgenetic (AG) mouse embryos survive after day 9.5 of pregnancy, owing to the inadequate growth of extraembryonic tissues, including the placenta. At day 9.5 of pregnancy, the placental structures are poorly developed in PG embryos, while trophoblast giant cells are abundant at the implantation site in AG embryos. These findings suggest that both parental genomes are required for placental development. To gain further insight into the trophoblast lineage in PG and AG embryos, we attempted to derive trophoblast stem (TS)-like cell lines from uniparental embryos. Furthermore, we sought to assess their ability to differentiate into cells of the trophoblast lineage by using gene expression analysis. Three cell lines that expressed marker genes for undifferentiated TS cells (Cdx2 and Errβ) were derived from AG embryos. Under differentiation conditions, these cells expressed the trophoblast giant cell-specific genes, but did not express the spongiotrophoblast-specific genes. In contrast, none of the four cell lines from PG embryos expressed marker genes for undifferentiated TS cells, but they expressed Oct3/4, a marker gene for embryonic stem cells. Immunohistochemical analysis indicated that PG blastocysts expressed Oct3/4 and Cdx2 specifically in inner cell mass and the trophectoderm respectively. These results suggest that PG embryos do not possess TS cells, because of the lack of the developmental ability of trophoblast cells.     

血红素氧化酶-1、2及内皮素-1在妊娠高血压综合征患者胎盘组织中的表达及作用

目的:通过观察妊娠高血压综合征(简称妊高征,PIH)患者胎盘组织血红素氧化酶-1、2(HO-1、2)及内皮素-1(ET-1)的表达,探讨PIH发病机制。方法:采用免疫组化SABC法,检测20例PIH患者及正常孕妇的胎盘绒毛组织中的HO-1、2及ET-1,利用免疫组化图象分析软件测量胎盘大绒毛、微绒毛合体滋养细胞及血管的平均吸光度。结果:妊高征组大绒毛、微绒毛合体滋养细胞及血管部位的HO-2表达显著低于正常孕妇组(P<0.001),HO-1在胎盘合体滋养细胞的表达显著低于正常孕妇组(P<0.001),而妊高征组大绒毛、微绒毛合体滋养细胞及血管部位的ET-1表达显著高于正常孕妇组(P<0.001);且H0-1、2在胎盘大绒毛、微绒毛合体滋养细胞的表达与平均动脉压呈负相关,而ET-1在胎盘大绒毛、微绒毛合体滋养细胞的表达与平均动脉压呈正相关。结论:妊高征患者胎盘组织血红素氧化酶的表达减少可能在妊高征的发生、发展过程中起着重要的作用。