TGF-β和IGF表达异常与滋养层相关疾病关系的研究

目的:探讨转化生长因子(TGF-β)和胰岛素样生长因子(IGF)等与滋养层侵入调节密切相关的细胞因子在胎盘绒毛组织中的表达,及与葡萄胎、先兆子痫等滋养层细胞相关妊娠疾病病理机制的关系。方法:采用半定量逆转录多聚酶链反应(RT-PCR)检测方法,分别以正常早孕绒毛和正常足月(自然分娩或剖宫产)胎盘绒毛组织为对照,观察葡萄胎组织与先兆子痫足月胎盘绒毛组织中TGF-β和IGF的表达。结果:5种胎盘绒毛组织中均可检测到IGF-I mRNA的表达,且先兆子痫足月胎盘绒毛组织中IGF-I的表达量明显低于正常足月胎盘绒毛组织,而葡萄胎组织中IGF-I的表达略高于正常早孕绒毛。在3种足月胎盘绒毛组织中可检测到IGF-ⅡmRNA的表达,但相互之间无明显差异。葡萄胎组织中IGF-Ⅱ的表达低于早孕绒毛。5种胎盘绒毛组织中均有TGF-β3的表达,而TGF-β1和TGF-β2的表达并未检测到。在表达量上,葡萄胎组织中TGF-β3的表达明显高于正常早孕绒毛组织,先兆子痫胎盘绒毛组织中TGF-β3的表达强于足月自然分娩的正常胎盘绒毛组织,而剖宫产胎盘绒毛组织中,TGF-β3的表达亦相对较强。结论:TGF-β3和IGF-I在胎盘绒毛组织中的表达变化,可能和葡萄胎、先兆子痫等与滋养层密切相关的妊娠疾病的发生有关。     

膜型基质金属蛋白酶表达与妊娠疾病的关系

目的 :研究葡萄胎和先兆子痫等与滋养层细胞密切相关的妊娠疾病在病理发生机制上与膜型基质金属蛋白酶表达的关系。方法 :采用逆转录多聚酶链反应 (RT PCR)检测方法 ,比较葡萄胎组织、早孕绒毛、先兆子痫足月胎盘和正常足月胎盘 (自然分娩和剖宫产 )组织中膜型基质金属蛋白酶 (MT MMP)的表达情况。结果 :5种胎盘绒毛组织均表达MT2 MMP和MT5 MMP。在相对表达量上 ,MT2 MMP及MT3 MMP在正常早孕绒毛组织中的表达强于葡萄胎组织 ,正常足月胎盘组织中MT2 MMP和MT5 MMP的表达也强于先兆子痫患者胎盘组织中 (P <0 .0 5 )。而自然分娩和剖宫产足月胎盘绒毛组织中MT2 MMP、MT3 MMP和MT5 MMP的表达差异均无显著性 (P >0 .0 5 )。结论 :MT2 MMP、MT3 MMP和MT5 MMP等膜型MMP在胎盘绒毛组织中的表达差异 ,与葡萄胎、先兆子痫等和滋养层密切相关的妊娠疾病的病理发生有关     

细胞外基质金属蛋白酶诱导因子在绒毛和胎盘组织中的表达

目的 探讨细胞外基质金属蛋白酶诱导因子(EMMPRIN)在绒毛及胎盘组织中的表达以及表达部位。方法 分别取36例妊娠6～9周妇女的早孕绒毛组织、7例因病理指征行中期引产妇女的胎盘组织和11例足月妊娠妇女的胎盘组织,免疫组化方法检测绒毛组织和胎盘组织中EMMPRIN的表达部位变化特点。结果 (1)表达部位：EMMPRIN在早孕绒毛组织、中期和足月妊娠的胎盘组织中均有高度表达。在早孕绒毛组织中的表达部位主要集中在绒毛内细胞滋养细胞、合体滋养细胞及细胞滋养层柱细胞;在中期和足月妊娠的胎盘组织中,主要表达于底蜕膜的绒毛外细胞滋养细胞。(2)表达特点：在早孕绒毛组织中细胞滋养细胞、合体滋养细胞和细胞滋养层柱细胞的。EMMPRIN阳性率随妊娠进展逐渐下降。在妊娠中期的胎盘组织中,细胞滋养细胞、合体滋养细胞和细胞滋养层柱细胞的EMMPRIN阳性率分别为5／7、3／7、5／7;在足月妊娠的胎盘组织中,细胞滋养细胞、合体滋养细胞和细胞滋养层柱细胞的EMMPRIN阳性率分别为73％、18％和82％。在中期和足月妊娠的底蜕膜中的EMMPRIN阳性率较弱,且趋于稳定。而早期妊娠阶段,侵入到底蜕膜的绒毛外细胞滋养细胞中。EMMPRIN阳性表达则随孕周进展逐渐增强。结论 EMMPRIN在妊娠早期与胚胎植入有关,在妊娠的中晚期则可能参与妊娠维持。     

先兆子痫或胎儿宫内发育迟缓的足月胎盘中合体滋养细胞凋亡增加

为探讨先兆子痫和胎儿宫内发育迟缓(IUGR)与胎盘合体滋养细胞凋亡增加的关系。对正常足月(妊娠37～38周剖宫产,组1)及严重先兆子痫和IUGR的足月(妊娠36～37周因不能控制的高血压或胎儿宫内窘迫行剖宫产,组2)胎盘各7例,用抗生物素/生物素免疫过氧化物酶方法检测其胎盘中Fas抗原和Bcl-2蛋白的表达。细胞凋亡采用TUNEL和透射电镜方法进行检测。TUNEL方法可在凋亡细胞出现形态学改变前发现,但由于它也识别坏死细胞的DNA片段,因此透射电镜对细胞超微结构的观察有利于鉴别。     

胎盘组织中尿皮素和促肾上腺皮质激素释放激素2β受体表达变化与先兆子痫发病的关系

目的探讨先兆子痫患者胎盘组织中尿皮素(UCN)和促肾上腺皮质激素释放激素2β受体(CRH R2β)表达与先兆子痫发病的关系。方法应用半定量RT PCR技术测定20例先兆子痫患者(先兆子痫组)和20例正常妊娠妇女(对照组)胎盘组织中UCNmRNA和CRH R2βmRNA的水平;采用免疫组化方法对UCN进行蛋白定位和半定量分析。结果(1)先兆子痫组胎盘组织中UCNmRNA的表达水平为1 14±0 26,高于对照组的0 78±0 46,两组比较,差异有统计学意义(P<0 05)。(2)先兆子痫组胎盘组织中CRH R2βmRNA的表达水平为0 89±0 33,与对照组的0 93±0 50比较,差异无统计学意义(P>0 05)。(3)免疫组化定位结果显示,两组产妇的UCN蛋白表达主要位于合体滋养细胞,少量表达于细胞滋养细胞和血管内皮细胞。蛋白半定量结果显示,UCN在先兆子痫组胎盘合体滋养细胞中的表达强度高于对照组,两组比较,差异有统计学意义(P<0 05 )。结论先兆子痫患者胎盘组织中UCN表达水平升高,而CRH R2β水平则无明显变化,因此UCN的作用加强。这可能是胎盘组织对母体和胎儿应激状态的一种继发性代偿反应,并参与先兆子痫的病理生理过程。     

脂联素在子痫前期患者胎盘组织中的表达与其发病的关系

目的 探讨脂联素在子痫前期患者胎盘组织中的表达与其发病的关系.方法 采用免疫组化链霉菌抗生物蛋白-过氧化物连接(SP)法及RT-PCR技术,检测20例正常足月妊娠孕妇(正常妊娠组)、12例轻度子痫前期(轻度子痫前期组)及22例重度子痫前期(重度子痫前期组)患者胎盘组织中脂联素蛋白及其mRNA的表达,并分析其与子痫前期发病的关系.结果 (1)3组孕妇胎盘绒毛合体滋养细胞及细胞滋养细胞胞质内脂联素蛋白均呈阳性表达,且各组内胎盘母面及子面脂联素蛋白的表达水平相互比较,差异均无统计学意义(P＞0.05).(2)重度子痫前期组胎盘组织中脂联素蛋白的表达水平(30 984±14 604)低于轻度子痫前期组(58 360±8910)及正常妊娠组(53 246±17 554),差异均有统计学意义(P＜0.01).重度子痫前期组中妊娠足月者胎盘组织中脂联素蛋白的表达水平(38 890±20 386)与未足月者(29 319±8997)比较,差异无统计学意义(P＞0.05);但与正常妊娠组比较,差异有统计学意义(P＜0.05).(3)3组孕妇胎盘组织中均有脂联素mRNA的表达.其中重度子痫前期组胎盘组织中脂联素mRNA表达水平(1.0±0.2)低于轻度子痫前期组(2.9±0.8)及正常妊娠组(3.3±1.1),差异有统计学意义(P＜0.05).结论 重度子痫前期患者胎盘组织中脂联素mRNA表达水平下降导致其蛋白表达水平也下降,提示脂联素的异常表达参与了子痫前期的发病.     

晚发型胎儿生长受限胎盘组织碱性成纤维细胞生长因子表达及超微结构的观察

目的:观察晚发型胎儿生长受限(fetal growth restriction,FGR)患者胎盘组织中碱性成纤维细胞生长因子(basic fibroblast growthfactor,bFGF)的表达及其超微结构的变化。方法:FGR组和足月正常妊娠组的胎盘组织标本各15例,应用免疫组织化学法检测bFGF的表达,2组标本各选取3例应用透射电镜观察其超微结构的变化。结果:2组均见bFGF表达于绒毛合体滋养层细胞、绒毛微血管内皮细胞和绒毛间质细胞的胞浆。FGR组胎盘滋养层bFGF的表达显著高于正常妊娠组(P<0.01)。FGR组胎盘合体结节增多,胎盘绒毛变性,基底膜增厚,微血管内皮可见突起及钙化砂粒体,自体胞质脱落。结论:FGR胎盘组织有超微结构病理改变,bFGF的表达可能是继发性增高。     

绒毛及合体滋养层细胞吲哚胺2,3-二氧化酶表达与流产的关系

目的:探讨人早孕绒毛组织吲哚胺2,3-二氧化酶(IDO)的表达与流产的关系。方法:RT-PCR测正常妊娠和难免流产绒毛组织及JAR细胞株IDOmRNA表达;免疫组化分析两组绒毛组织IDO蛋白质表达;Westernblot检测体外培养的合体滋养层细胞IDO蛋白质表达;高效液相色谱法检测细胞培养上清液中有无犬尿氨酸。结果:难免流产组绒毛组织IDOmRNA及蛋白质表达均低于正常组;JAR细胞株不表达IDOmRNA;合体滋养层细胞表达IDO蛋白质;合体滋养层细胞培养上清中有犬尿氨酸。结论:绒毛组织IDO正常表达是维持妊娠所必需;体外培养的人早孕绒毛合体滋养层细胞表达的IDO具有活性。     

先兆子痫分娩时蜕膜和胎盘组织的VEGFmRNA无变化

为了解先兆子痫者内皮细胞系统功能改变及血管内皮生长因子(VEGF)对缺氧产生应答,对足月分娩时,先兆子痫患者与正常妊娠对照组底蜕膜及胎盘组织的VEGF mRNA水平进行对照研究。 研究组为无其他妊娠并发症的先兆子痫患者,对照组为     

血管生长因子受体3(VEGFR3)在胎盘的细胞定位及其在ART安全性研究中的意义

目的:探讨血管生长因子受体3(vascular endothelial growth factor 3,VEGFR3)在ART妊娠胎盘组织中的差异表达及其安全性研究中的意义。方法:收集11例自然妊娠(对照组)和10例ART妊娠(ART组)的单胎足月妊娠选择性剖宫产分娩的胎盘组织,分析比较组间的临床资料;并应用免疫组织化学技术和实时荧光定量PCR技术,观察VEGFR3在胎盘组织的细胞定位,比较VEGFR3在ART和对照组胎盘组织中的差异表达。结果:VEGFR3在胎盘组织中定位于胎盘绒毛合体滋养层细胞胞质。与对照组相比,VEGFR3细胞定位一致,ART妊娠的胎盘组织中VEGFR3 mRNA表达水平有上升趋势,但无统计学差异(P>0.05)。结论:ART妊娠的胎盘组织中VEGFR3细胞定位和表达水平未见明显变化。     

Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation.

OBJECTIVE: This study was undertaken to determine whether preeclampsia and intrauterine growth retardation are associated with an increase in placental apoptosis. STUDY DESIGN: Tissue specimens from 7 normal term placentas and each of 7 term placentas complicated by severe preeclampsia or intrauterine growth retardation were analyzed. Fas antigen and Bcl-2 protein expression were examined by the avidin/biotin immunoperoxidase method, whereas apoptosis was assessed by the terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) method and transmission electron microscopy. RESULTS: Fas antigen was immunolocalized in syncytiotrophoblasts in all placentas examined. No changes in the intensity of Fas antigen immunostaining in syncytiotrophoblasts were apparent among those placentas. Bcl-2 protein was abundantly immunolocalized in syncytiotrophoblasts in normal term placentas, but least abundant in term placentas complicated by severe preeclampsia or intrauterine growth retardation. Apoptosis was apparent in the nuclei of both cytotrophoblasts and syncytiotrophoblasts. The apoptosis positive rate of syncytiotrophoblast nuclei in severe preeclamptic and intrauterine growth retardation term placentas was significantly higher than that in normal term placentas (severe preeclampsia, P <.001; intrauterine growth retardation, P <.01). Transmission electron microscopy revealed the appearance of apoptotic nuclei in trophoblasts in severe preeclamptic term placenta. CONCLUSION: Decreased expression of Bcl-2 protein in syncytiotrophoblasts in severe preeclamptic and intrauterine growth retardation placentas may result in the increase in apoptosis in syncytiotrophoblasts in those placentas.     

Expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in human preeclamptic placenta: possible implications in the process of trophoblast apoptosis

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was originally identified as a receptor for oxidatively modified low-density lipoprotein. It has been reported that oxidative stress and hyperlipidemia play important roles in the etiology of preeclampsia, and that placental oxidative stress may stimulate syncytiotrophoblast apoptosis in preeclampsia. In this study, we examined the expression of LOX-1 in the human placentas of normal pregnancies and in preeclampsia using immunohistochemistry and Western blot analysis, and proposed that LOX-1 has a role in trophoblast apoptosis. To analyze apoptotic activity, the expression of the specific caspase cleavage site within cytokeratin 18 was assessed immunohistochemically using the monoclonal antibody M30 CytoDeath. Both LOX-1 and M30 immunoreactivity occurred predominantly in syncytiotrophoblasts. A significantly higher number of LOX-1 and M30-positive cells were found in preeclamptic placentas than in normal placentas. The number of M30-positive cells correlated with the apoptotic index of trophoblasts determined by TdT-mediated dUTP nick-end labeling (TUNEL). Syncytiotrophoblasts showing apoptotic activity were immunopositive to LOX-1 by double immunohistochemical fluorescence. We suggest that the functional role of syncytiotrophoblasts in placental dysfunction results from the localization and upregulation of LOX-1 in the preeclamptic placenta, possible implications in upregulation of syncytiotrophoblast apoptotic activity in preeclampsia.     

PKC delta in preeclamptic placentas promotes Bax dissociation from 14-3-3 zeta through 14-3-3 zeta phosphorylation

OBJECTIVE: We investigated placental apoptosis and the expression of and interactions between 14-3-3 and Bcl-2 family proteins during preeclampsia. In addition, we explored the mechanism of Bax dissociation from 14-3-3, hypothesizing that PKC-mediated phosphorylation of 14-3-3 results in dissociation of Bax from 14-3-3 proteins, and leads to apoptosis. METHODS: Placental samples from 10 women with preeclampsia and 10 normotensive control patients were analyzed using M30-specific immunohistochemistry to assess placental apoptosis. Biochemical markers of cellular apoptosis, such as cleaved caspase-3, Bax, Bcl-2, 14-3-3, and PKC were followed by Western blotting. Interaction of 14-3-3 proteins with Bax and with PKC was assessed by immunoprecipitation. RESULTS: M30-positive cells were widespread in the preeclamptic placentas. The levels of cleaved caspase-3, Bax, 14-3-3 zeta, phospho-(Ser)-14-3-3, and PKC delta were significantly higher in the preeclamptic placentas than in normal placentas. Preeclampsia was also associated with weaker interactions between 14-3-3 zeta and Bax and stronger interactions between 14-3-3 zeta and PKC delta. CONCLUSION: Our results suggest that PKC delta in preeclamptic placentas promotes Bax dissociation from 14-3-3 zeta through the phosphorylation of 14-3-3 zeta. This finding may at least in part explain the apoptosis-inducing activity of PKC delta, revealing the important role of PKC delta in the development of apoptosis-related diseases such as preeclampsia.     

Homocysteine thiolactone induces apoptosis in cultured human trophoblasts: a mechanism for homocysteine-mediated placental dysfunction?

OBJECTIVE: Hyperhomocystinemia is a thrombophilic condition associated with placental dysfunction. We tested the hypothesis that homocysteine-thiolactone, a metabolite of homocysteine, induces apoptosis in cultured trophoblasts. STUDY DESIGN: Cytotrophoblasts from term human placentas were cultured for 72 hours or less in the presence or absence of 50 to 400 micromol/L homocysteine-thiolactone or 400 micromol/L cysteine (control), with or without vitamin C, vitamin E, folate, or N-acetylcysteine. Cell death was assessed by cellular adenosine triphosphate concentration, medium lactate dehydrogenase level, and immunocytochemical staining for the cleavage products of cytokeratin 18 and poly(adenosine diphosphate ribose) polymerase. Changes in expression of p53, Bcl-2, Bax, and Bak were quantified by Western immunoblotting. RESULTS: Homocysteine-thiolactone induced a concentration dependent increase in total cell death and death by apoptosis, compared with control. Vitamin C ameliorated apoptosis in cytotrophoblasts, whereas N-acetylcysteine mitigated cell death in syncytiotrophoblasts. Apoptosis in both phenotypes occurred with increased expression of p53 and Bak, but no change in Bcl-2 or Bax. CONCLUSION: Homocysteine-thiolactone enhances apoptosis in cultured human trophoblast, and the effect can be limited by antioxidants.     

正常妊娠及妊高征孕妇胎盘组织中细胞凋亡及增殖基因表达的研究

目的 :探讨正常妊娠及妊高征 (PIH)孕妇胎盘组织bcl - 2、bax及ki6 7基因的表达及其相互关系。方法 :采用免疫组化方法测定正常早、中、晚期妊娠 30例及轻、中、重度PIH 36例的胎盘组织bcl - 2、bax及ki6 7的表达。结果 :(1)bcl - 2表达主要定位在绒毛的合体滋养层细胞 (S -cells) ,而bax在S -cells和细胞滋养层细胞 (C -cells)均呈阳性 ,在绒毛间质中bax也呈阳性表达 ,但强度低于滋养层细胞。ki6 7定位于C -cells;(2 )bcl - 2在晚期妊娠组的阳性率低于早、中期妊娠组 (P <0 .0 5 )。ki6 7在正常早、中、晚期妊娠组 ,对照组与PIH组 ,轻、中、重度PIH组之间均有显著性差异 (P <0 .0 1) ;(3)bcl - 2和bax表达及与ki6 7的表达无相关性 (P >0 .0 5 )。结论 :bcl - 2及bax在高水平上达到平衡 ,在胎盘组织中并不起介导细胞凋亡的主导作用 ,而且二者的表达不影响细胞的增殖     

子痫前期及正常妊娠孕妇胎盘组织PTEN表达的研究

目的:研究PTEN在子痫前期胎盘组织及正常妊娠胎盘组织中的表达以探讨其与子痫前期发病的关系。方法:通过逆转录聚合酶链反应法检测37例重度子痫前期、22例轻度子痫前期及53例正常妊娠胎盘组织中PTEN的核酸表达水平,运用免疫组织化学检测PTEN在胎盘组织中的定位,通过免疫印迹法检测PTEN蛋白表达的水平。结果:免疫组织化学技术显示,PTEN选择性表达于胎盘血管内皮细胞浆中,RT-PCR及免疫印迹结果显示:重度子痫前期胎盘组织中PTEN的表达量低于轻度子痫前期及正常妊娠,差异有统计学意义(P<0.05)。结论:与正常妊娠及轻度子痫前期相比,重度子痫前期时PTEN表达发生改变,提示PTEN在重度子痫前期的发病机制中可能发挥了作用。     

妊娠期高血压疾病患者胎盘组织中溶血磷脂酸受体蛋白Edg4、7的表达及其意义

目的 探讨胎盘组织中溶血磷脂酸受体蛋白Edg4、7的表达与妊娠期高血压疾病发生的关系及作用机制。方法 采用免疫组化链霉菌抗生物素蛋白-过氧化物酶（SP）法,检测20例正常晚期妊娠妇女（正常晚孕组）、20例妊娠期高血压患者（妊娠期高血压组）、20例轻度子痫前期患者（轻度子痫前期组）、30例重度子痫前期患者（重度子痫前期组）的胎盘组织中溶血磷脂酸受体蛋白Edg4与Edg7的表达。结果（1）表达部位：Edg4与Edg7主要表达于胎盘绒毛滋养细胞及蜕膜细胞的细胞质和细胞膜。（2）Edg4和Edg7在胎盘绒毛滋养细胞中的表达阳性率：正常晚孕组分别为25％和20％,妊娠期高血压组分别为60％和40％,轻度子痫前期组分别为80％和65％,重度子痫前期组分别为83．3％和86,7％。轻、重度子痫前期组阳性率明显高于正常晚孕组,两组分别比较,差异有统计学意义（P〈0,05）;妊娠期高血压组与正常晚孕妇组比较,差异无统计学意义（P〉0．05）。（3）Edg4和Edg7在胎盘蜕膜细胞中的表达阳性率：正常晚孕组分别为20％和25％,妊娠期高血压组分别为55％和50％,轻度子痫前期组分别为70％和55％,重度子痫前期组分别为83．3％和73．3％。轻度子痫前期组及重度子痫前期组阳性表达率明显高于正常晚孕组,两组分别比较,差异有统计学意义（P〈0．05）;妊娠期高血压组与正常晚孕组比较,差异无统计学意义（P〉0．05）。结论 妊娠期高血压疾病患者胎盘组织中溶血磷脂酸受体蛋白Edg4、7呈高表达,提示溶血磷脂酸与胎盘组织中的特异性受体Edg4、7结合,并参与了妊娠期高血压疾病的发生。     

Expression of NADPH oxidase isoform 1 (Nox1) in human placenta: involvement in preeclampsia

Increased oxidative stress in the placenta has been associated with preeclampsia (PE), a clinical syndrome involving placental pathology. The enzymatic sources of reactive oxygen species in the human placenta are as yet unidentified. We hypothesized that NADPH oxidase is a main source of reactive oxygen species in the placenta and its expression may change in PE. Employing RT-PCR, we have amplified a novel NADPH oxidase isoform Nox1 from human choriocarcinoma BeWo cells. Using polyclonal anti-peptide antiserum recognizing unique Nox1 peptide sequences, we identified by immunohistochemistry and cell fractionation that Nox1 protein localizes in the BeWo cell membrane structures. Immunohistochemistry of normal placental tissues showed that Nox1 was localized in syncytiotrophoblasts, in villous vascular endothelium, and in some stromal cells. At the immunohistochemical level Nox1 expression was significantly increased in syncytiotrophoblast and endothelial cells in placentas from patients with preeclampsia as compared to gestational age-matched controls. Western blot analysis of whole placental homogenate confirmed this increase. Our data suggests that increased Nox1 expression is associated with the increased oxidative stress found in these placentas.     

Apoptosis and differential expression of apoptosis-related proteins in endometriotic glandular and stromal cells

OBJECTIVE: Apoptosis is an important regulator of eutopic endometrial function. Endometriosis, the growth of endometrial tissue outside the uterus, could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. The objective of this study was to evaluate the rate of apoptosis and the expression of apoptosis-related Bcl-2 and Bax proteins in endometriotic tissues within the glandular and stromal compartments, according to the phase of the menstrual cycle and the stage of disease. METHODS: Ovarian endometriosis samples were evaluated in 75 women who had surgery at a university hospital. Apoptotic cells were detected with the use of the dUTP nick-end labeling (TUNEL) assay. Bcl-2 and Bax expression were assessed by immunohistochemical techniques. RESULTS: The percentage of apoptotic cells was significantly higher in endometriotic stromal cells (73.3%) compared with glandular cells (48%; P =.002). In contrast, the expression of the apoptosis-related proteins Bcl-2 and Bax was significantly lower in the endometriotic stroma (17.3% for both) than in the glandular epithelium (38.6% and 41.3%, respectively; P <.004). No significant menstrual cycle phase-dependent changes or endometriosis stage-related changes were observed in TUNEL, Bcl-2, or Bax positivity within ovarian endometriotic tissues. CONCLUSION: Apoptosis occurs in ovarian endometriotic lesions at significantly higher levels in the stroma than the glandular epithelium. However, Bcl-2 and Bax proteins are distributed preferentially in glandular epithelial cells. The apoptotic rate as well as Bcl-2 and Bax expression in ovarian endometriotic cells were not affected by the stage of endometriosis or the phase of the menstrual cycle.