HTLV-I transmission from mother to child

Human T-lymphotropic virus type I (HTLV-I), a causative agent of adult T-cell leukemia, (ATL) is transmitted from mother to child. ATL cells originate from the CD4 subset of peripheral T cells. The main route of mother-to-child transmission is postnatal breast-feeding. Refraining from breast-feeding or limiting the duration of breast-feeding can reduce the risk of mother-to-child transmission. Other than postnatal breast-feeding, there seem to be two routes of HTLV-I transmission from mother to child. One is intrauterine transmission, and the other is via saliva. Intrauterine transmission is rare, although proviral DNA is detected in cord blood samples. HTLV-I proviruses in the cord blood may be defective. HTLV-I proviral DNA and antibodies against HTLV-I are also detected in saliva. However, no report has been published so far which showed direct evidence of HTLV-I transmission via saliva. The placenta can be infected by HTLV-I, but infection does not reach the fetus, possibly apoptosis of placental villous cells because it is induced by HTLV-I infection.     

胎盘乙型肝炎病毒感染与宫内传播的关系

目的 探讨乙型肝炎病毒（ＨＢＶ）宫内传播的危险因素,并追踪ＨＢＶ经胎盘传播的途径和胎儿宫内感染的时间,方法 共收集了乙型肝炎表面抗原（ＨＢｓＡｇ）携带孕妇１３１例,其中孕早期人工流产胎盘２４例,孕中期引产胎盘和胎儿各６例,足月分娩胎盘和新生儿各１０１例。孕妇和新生儿血清ＨＢｓＡｇ和ＨＢＶ ＤＮＡ检测分别采用酶联免疫吸附试验和聚酶链反应法。     

妊娠中晚期乙型肝炎表面抗原阳性妇女胎盘感染的研究

目的 探讨乙型肝炎表面抗原（ＨＢｓＡｇ）阳性妇女妊娠中晚期胎盘各层细胞的乙型肝炎病毒感染状况。方法 收集太原市传染病医院妇产科ＨＢｓＡｇ阳性产妇胎盘１６７例（其中足月分娩胎盘１５８例,中期引产胎盘９例）,用免疫组织化学ＡＢＣ染色法检测胎盘蜕膜细胞、滋养层细胞、绒毛间质细胞和绒毛毛细血管内皮细胞ＨＢｓＡｇ和乙型肝炎核心抗原（ＨＢｃＡｇ）。结果 （１）足月分娩胎盘蜕膜细胞、滋养层细胞、绒毛间质细胞和绒毛毛细血管内皮细胞均感染乙型肝炎病毒,以胞浆分布为主,局灶性分布多见。从蜕膜细胞、滋养层细胞、盈盘间质细胞至绒毛毛细血管内皮细胞,乙型肝炎病毒感染率呈下降趋势,总感染率分别为６６．４６％（１０５／１５８）、５８．２３％（９２／１５８）、２７．２２％（４３／１５８）和１２．６６％（２０／１５８）。（２）中期引产胎盘有１例     

Role of placental tissues in the intrauterine transmission of hepatitis B virus

OBJECTIVE: The purpose of this study was to determine the mechanism of intrauterine transmission of hepatitis B virus. STUDY DESIGN: Placental tissues from 158 pregnant women who tested positive for hepatitis B surface antigen were examined for hepatitis B virus markers, Fc gamma receptors, and hepatitis B surface antigen-anti-hepatitis B surface antigen in different layers of cells. RESULTS: It was shown that the hepatitis B virus infection rate among different layers of placental cells gradually decreased from the maternal side to the fetal side. Furthermore, the closer the infected cell layer was to the fetal side, the higher the risk of intrauterine hepatitis B virus infection. Fc gamma receptors were found on cells of both hepatitis B surface antigen positive and negative placentas; Fc gamma receptors III were found on trophoblastic cells and villous mesenchymal cells, and Fc gamma receptors II were found on only villous mesenchymal cells. Hepatitis B surface antigen-antibodies to hepatitis B surface antigen was detected in the cytoplasm and on the membrane of trophoblastic cells and villous mesenchymal cells in 2 hepatitis B surface antigen-positive placentas. CONCLUSION: The results support the hypothesis that intrauterine hepatitis B virus transmission could be caused through "cellular transfer" in the placenta. One of the means of cellular transfer could be through Fc gamma receptor III-mediated entry of hepatitis B surface antigen-antibodies to hepatitis B surface antigen into cells.     

Influence of maternal diabetes on placental fibroblast growth factor-2 expression, proliferation, and apoptosis

OBJECTIVE: Type I diabetes mellitus during pregnancy is associated with dysregulation of the oxygen and glucose metabolic pathways, both of which affect placental villous growth and function. Alteration of placental development in women with diabetes may contribute to the increased risk of preeclampsia, macrosomia, or fetal growth restriction. METHODS: To evaluate placental growth in the setting of maternal diabetes, immunohistochemical techniques were used to examine fibroblast growth factor-2 (FGF-2) expression, cell proliferation (Ki67), and apoptosis (Apo-Tag) in placentas from diabetic and nondiabetic patients. RESULTS: Immunostaining for FGF-2 in placentas from diabetic women demonstrated an increase in intensity within the villous stroma and syncytiotrophoblast (P<.05). Associated with these changes in FGF-2 expression, placentas from diabetic women showed no change in villous mitotic activity but did show decreased stromal compartment apoptosis. When expressed as a ratio of Ki67-positive:Apo-Tag-positive nuclei as an index of relative cell turnover, the stromal compartment showed a significant trend towards decreased nuclei turnover (P<.05), suggesting relative tissue growth in diabetic patients. CONCLUSION: Increased FGF-2 expression and decreased stromal cell compartment turnover in the diabetic placenta might be a compensatory mechanism in response to the altered physiologic milieu of maternal diabetes on placental function.     

The significance of morphologic placental findings in fetal distress

The causes of fetal distress are analyzed in 50 cases, with special emphasis being placed upon placental insufficiency. Clinically, no cause can be found for the condition of danger to the fetus in 8 pregnant women. The surface of the villous vessels evaluated by morphometric methods is significantly decreased in 10 placentas. Of the 8 pregnant women without known cause of fetal distress, 3 cases were found to show reduced villous vascularization. The relevance of morphological examinations of the placenta in fetal distress is discussed.     

Expression of receptors for tumor necrosis factor in human placenta at term.

The biological effects of tumor necrosis factor (TNF) are mediated through its interaction with high affinity receptors on target cells. Secretion of soluble cytokine receptors has been suggested as a mechanism of regulating cytokine activity in vivo. In a previous study we detected soluble TNF receptors (TNFRs) in amniotic fluid and urine samples from pregnant women, suggesting that secretion of soluble TNFRs may provide a mechanism for protection of the fetus against TNF action during pregnancy. In the present study, TNFR containing cells in cryostat sections from normal placentas at term were evaluated by monoclonal antibodies against the 55 kD--and the 75 kD TNFR in an indirect immunofluorescence technique. The 55 kD TNFR was expressed by the villous syncytiotrophoblasts, by vascular endothelial cells, by some decidual cells and by occasional cells in the placental stroma. Staining for the 75 kD TNFR was confined to the vascular endothelial cells, a relatively small number of stromal cells and decidual cells, whereas the villous syncytiotrophoblasts were negative. The abundant expression of TNFRs in placental tissue suggests: 1. That a considerable number of the placental cells are receptive to the regulatory activities of TNF; 2. That placental cells may be the cellular origin of soluble TNFRs secreted during pregnancy.     

胎盘提前钙化的超声征象与胎盘细胞凋亡的关系

目的:探讨胎盘细胞凋亡在胎盘提前钙化发生发展中的作用。方法:选择15例在36周前B超检查发现Ⅲ级胎盘成熟度的低风险孕妇作为研究组,随机选择同期分娩孕龄与研究对象相匹配的正常孕妇15例作为时照。采用光镜和TUNEL法观察计数细胞凋亡现象。结果:在两组胎盘组织中均可观察到凋亡细胞,提前钙化组细胞凋亡发生率的中位数及四分位数范围为0．57%(0．33%,0．46%),正常对照组为0．23%(0．10%, 0．23%),二者差异有统计学意义(P＜0．001)。结论:提前钙化胎盘组织中细胞凋亡增多,细胞凋亡可能在胎盘提前钙化的发生发展过程中起了重要作用。     

胎盘生长因子与子痫前期发病及一氧化氮关系的研究

目的:探讨胎盘生长因子(PLGF)在子痫前期发病中的作用及其与一氧化氮的关系。方法:选择妊娠期高血压疾病患者45例,其中妊娠期高血压10例,轻度子痫前期12例,重度23例;选择同期正常妊娠妇女20例作为对照组。采用免疫组织化学染色法和逆转录-聚合酶链式反应(RT-PCR)检测两组患者胎盘PLGF蛋白及mRNA的表达。采用硝酸盐还原酶法测定两组胎盘组织NO浓度的变化。结果:(1)免疫组化结果显示,轻度和重度子痫前期的胎盘绒毛合体滋养细胞、绒毛间质PLGF表达均显著低于正常妊娠组(P<0.05),妊娠期高血压组与正常组无差别;PLGF在妊娠期高血压、子痫前期组及正常妊娠组分布范围基本一致,主要分布在绒毛合体滋养细胞和间质细胞胞浆,部分血管合体膜上也有表达;(2)轻、重度子痫前期胎盘组织PLGF mRNA平均灰度分别为3.33±0.39、1.97±0.29,显著低于正常妊娠组的平均灰度4.87±0.60(P<0.01);(3)轻、重度子痫前期胎盘组织中NO浓度分别为8.20±5.56μmol/g、6.46±2.25μmol/g,显著低于对照组18.10±7.12μmol/g(P<0.05);妊娠期高血压组胎盘组织NO浓度与对照组差异无显著性;(4)胎盘组织中胎盘生长因子表达水平与胎盘组织NO浓度呈显著正相关(r=0.54,P<0.05)。结论:子痫前期胎盘组织中胎盘生长因子水平降低,NO浓度下降,可能在子痫前期的发病中起一定作用。     

先兆子痫患者母胎界面上细胞凋亡的研究

目的:研究先兆子痫患者母胎界面上细胞凋亡水平及凋亡相关分子的表达变化。方法:分别收集妊娠25、27、29、30和31周及足月分娩的正常妊娠者和先兆子痫患者的胎盘组织,采用脱氧核糖核酸末端转移酶介导的dUTP刻痕末端标记法(TUNEL)检测母胎界面上细胞凋亡情况, 并行凋亡细胞定位;RT-PCR检测正常妊娠和先兆子痫胎盘组织中P53,Bcl-2和Bax的mRNA表达水平的差异。结果:正常妊娠和先兆子痫患者胎盘中发生凋亡的细胞数目都随孕周延长而逐渐增高,但先兆子痫的胎盘中细胞凋亡率明显高于正常妊娠者;正常妊娠胎盘中凋亡细胞主要为合体滋养层细胞,足月胎盘绒毛内血管内皮细胞亦有少量细胞凋亡,而先兆子痫胎盘中细胞滋养层细胞、合体滋养层细胞和绒毛内血管内皮细胞均发生明显的凋亡;RT-PCR显示先兆子痫胎盘组织中P53和Bax的mRNA水平明显高于同期妊娠的正常胎盘,而Bcl-2水平显著降低。结论:正常妊娠过程中胎盘组织中只在有限部位出现少量细胞凋亡,而先兆子痫胎盘组织中细胞过度凋亡, 且凋亡细胞分布广泛,并伴有凋亡相关分子的表达上调。表明先兆子痫的发生与胎盘组织中滋养层细胞大量凋亡密切相关。     

Viral infection,proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection

Purpose

Attention is increasingly focused on the potential mechanism(s) for Zika virus infection to be transmitted from an infected mother to her fetus. This communication addresses current evidence for the role of the placenta in vertical transmission of the Zika virus.

Methods

Placentas from second and third trimester fetuses with confirmed intrauterine Zika virus infection were examined with routine staining to determine the spectrum of pathologic changes. In addition, immunohistochemical staining for macrophages and nuclear proliferation antigens was performed. Viral localization was identified using RNA hybridization. These observations were combined with the recent published results of placental pathology to increase the strength of the pathology data. Results were correlated with published data from experimental studies of Zika virus infection in placental cells and chorionic villous explants.

Results

Placentas from fetuses with congenital Zika virus infection are concordant in not having viral-induced placental inflammation. Special stains reveal proliferation and prominent hyperplasia of placental stromal macrophages, termed Hofbauer cells, in the chorionic villi of infected placentas. Zika virus infection is present in Hofbauer cells from second and third trimester placentas. Experimental studies and placentae from infected fetuses reveal that the spectrum of placental cell types infected with the Zika virus is broader during the first trimester than later in gestation.

Conclusions

Inflammatory abnormalities of the placenta are not a component of vertical transmission of the Zika virus. The major placental response in second and third trimester transplacental Zika virus infection is proliferation and hyperplasia of Hofbauer cells, which also demonstrate viral infection.

     

雌激素受体α在子痫前期胎盘的表达及临床意义

目的:通过比较雌激素受体α(ERα)在子痫前期胎盘和正常胎盘中组织细胞的定位,探讨ERα与子痫前期疾病的相关性及其临床意义。方法:用免疫组化SP法检测28例正常足月妊娠胎盘组织和33例子痫前期胎盘组织中ERα的表达。结果:免疫组织化学结果显示两组的ERα均呈阳性表达,子痫前期组的ERα在胎盘细胞滋养细胞的细胞质内或细胞核内的阳性表达率高于正常孕妇组(P<0.05)。结论:免疫组化检查定位于胎盘绒毛细胞滋养细胞、绒毛毛细血管管壁细胞和绒毛间质纤维组织成纤维细胞的ERα作为实现雌激素功能的介导中枢,可能通过调控雌激素的作用参与了子痫前期的发生和发展过程。     

乙型肝炎病毒感染胎盘组织差异表达基因的筛选与确定

目的了解乙型肝炎病毒（HBV）感染胎盘组织基因表达的改变,确定与HBV感染胎盘相关的基因,以探讨HBV宫内感染的分子机制。方法选择2002年1月至2003年12月,在西安交通大学第一医院未临产以剖宫产分娩的30例HBsAg、HBVDNA双阳性（实验组）和30例HBsAg、HBVDNA双阴性（对照组）妇女的胎盘组织,采用抑制消减杂交技术（SSH）建立HBV感染胎盘组织cDNA消减文库,经反向斑点杂交技术证实差异表达基因。RT-PCR验证部分基因在HBV感染胎盘组织中的表达。结果两组差异表达基因35个,对其中含有插入片段的阳性克隆进行测序分析,获得33个已知基因序列,两个未知基因;并初步判定磷脂酰肌醇3激酶（PBK）基因在HBV感染的胎盘组织中表达明显增强。结论HBV感染胎盘时,基因表达可发生明显变化;PBK基因表达变化,对了解HBV宫内感染的分子机制有重要意义。     

Reduced amount of cytochrome c oxidase subunit I messenger RNA in placentas from pregnancies complicated by preeclampsia

BACKGROUND: Cytochrome c oxidase is a marker enzyme of the mitochondrial inner membrane. A change in the structure and activity of cytochrome c oxidase may alter the electron transport in the inner membrane, leading to insufficient adenosine triphosphate (ATP) production. ATP is essential for maintaining the function of cells. The aim of this study was to compare the expression of cytochrome c oxidase subunit I mRNA in placentas from normal and preeclamptic pregnancies. METHODS: By means of in situ hybridization, frozen sections of placentas from 23 women with preeclampsia and 29 women with uneventful pregnancies were examined. Digoxigenin (DIG)-labeled probes were used to detect the expression of cytochrome c oxidase subunit I mRNA in the placentas. The expression density was assessed by using an image disposal and analysis system. RESULTS: Positive expression of cytochrome c oxidase subunit I mRNA was found in the cytoplasm of villous syncytiotrophoblasts. The mean light density of cytochrome c oxidase subunit I mRNA in placental villi of normal pregnant women was 0.2638, and 0.1763 in women with preeclampsia, a statistically significant difference (P < 0.05). The number density of cytochrome c oxidase subunit I mRNA in placental villi was also significantly reduced in preeclamptic women compared with the control group (P < 0.05). CONCLUSIONS: Our study demonstrates a reduced amount of cytochrome c oxidase subunit I mRNA in preeclamptic placentas compared to control placentas. We hypothesize that a reduced expression may play a role in the pathophysiology of preeclampsia.     

妊娠期糖尿病胎盘微绒毛形态计量学改变与围产儿并发症关系的探讨

目的:探讨妊娠期糖尿病胎盘绒毛变化与围产儿并发症的关系。方法:选择足月妊娠期糖尿病38例的胎盘为观察组,选择正常足月妊娠30例的胎盘为对照组,分娩时在胎盘母面取材,制成快速脱水、表面喷金镀膜标本,在扫描电镜下用VIDAS型图像分析仪对胎盘微绒毛进行组织形态计量学测定。称取胎盘重量、计算胎盘系数(胎盘重量与新生儿出生体重比值),记录新生儿Apgar评分、体重、脐血胆红素及新生儿出生后30min内血糖值。结果:糖尿病孕妇的胎盘合体滋养层细胞微绒毛面积、周长、长轴、短轴小于对照组,差异均有统计学意义(P<0.05);异形指数大于对照组,差异有统计学意义(P<0.05)。扫描电镜下观察组胎盘组织超微结构病理变化明显,表现为胎盘绒毛成熟不良、水肿,合体滋养层表面微绒毛排列紊乱,直径大小不一,局部缺损,呈葡萄状。观察组胎盘重量明显高于对照组,两组差异显著(P<0.05)。胎盘系数两组间差异非常显著(P<0,01);两组新生儿窒息、出生30min内血糖值、血胆红素均有显著差异(P<0.01)。结论:妊娠期糖尿病胎盘病理变化进一步加重了胎儿缺氧,增加了新生儿窒息率,导致新生儿发生更多的并发症。     

Placental alkaline phosphatase (PLAP) study in diabetic human placental villi infected with Trypanosoma cruzi

Previous work has demonstrated that PLAP activity decreases in serum and placental villi from term chagasic and diabetic pregnant women. In vitro, T. cruzi induces changes in human syncytiotrophoblast's PLAP. Our aim was to determine if infection with T. cruzi induces changes in PLAP activity in diabetic and chagasic women's placenta, in order to elucidate if PLAP plays a role in the mechanisms of interaction between placenta and T. cruzi, and whether hyperglycemic conditions could worsen the placental infection. Using zymogrammes, Western blot, biochemical and immunohistological techniques, PLAP activity was determined in placental villi from diabetic and chagasic women, and in normal placentas cultured under hyperglycemic conditions with or without trypomastigotes. A significant reduction of PLAP expression was immunologically detected in infected diabetic and normal placental villi cultured under hyperglycemic conditions of 71 and 81%, respectively, compared with controls. A significant decrease of PLAP specific activity was registered in homogenates and in the culture media from both infected diabetic and normal placentas under hyperglycemic conditions (of about 50-70%), and in chagasic ones (of about 87%), when compared with controls. Thus, PLAP might be involved in parasite invasion and diabetic and hyperglycemic placentas could be more susceptible to T. cruzi infection.     

Effect of placental hypoxia on the plasma membrane Ca-ATPase (PMCA) activity and the level of lipid peroxidation of syncytiotrophoblast and red blood cell ghosts

Term placental villous fragments from normotensive pregnant women were incubated under hypoxia in order to induce lipid peroxidation of the placental plasma membranes and, consequently, to increase their release of lipid peroxide products into the incubation medium. The homogenates of the villous fragments were assayed for plasma membrane Ca-ATPase (PMCA) activity and TBARS. The incubation medium, after placental hypoxia, was used to incubate intact red blood cells (RBCs) from normotensive pregnant women. Similarly, intact RBCs from normotensive pregnant women were incubated with deproteinized blood plasma from normotensive pregnant women and women with preeclampsia. In all the cases, red cell ghosts were prepared from the incubated cells and assayed for PMCA and TBARS. The incubation of placental villous fragments under hypoxia led to an increase in the TBARS and a significant reduction in the PMCA activity of their homogenates, as compared to those of villous fragments incubated under normoxia. The exposure of intact RBCs from normotensive pregnant women either to the incubation medium of placental hypoxia or to deproteinized blood plasma from women with preeclampsia, caused a rise of the TBARS and a diminution of PMCA activity of the red cell ghosts. Inside-out vesicles were also prepared from intact RBCs incubated with the medium where the placental hypoxia was carried out. These vesicles were assayed for active calcium transport. Pretreatment of RBCs with the incubation medium of placental hypoxia led to a lower active calcium transport as compared to that of inside-out vesicles from RBCs without any preincubation. These results are in agreement with the idea that the RBCs can be peroxidized when passing through a highly oxidized medium, such as the placental intervillous space from women with preeclampsia. The peroxidized RBCs would contribute then to the propagation of lipid peroxidation from the placenta to nearby and far away tissues.     

Human papillomavirus in the cervix and placenta

OBJECTIVE: To determine the prevalence and association of human papillomavirus (HPV) infection in the cervices and placentas of pregnant women. METHODS: Cervical samples were taken from 179 of 226 women who had placental biopsies because of abnormal ultrasound findings or were older than 35 years, to detect HPV infections with hybrid capture II tests. Polymerase chain reaction (PCR) was done on placental tissue of 147 of the 226 women to detect HPV DNA. RESULTS: We found 44 of 179 women (24.6%, 95% confidence interval 18.3, 31.0) to test positive for HPV in their cervices. Logistic regression analyses showed decreased prevalence of HPV infection with increased maternal age (P =.039). The HPV DNA E6 PCR from the villus tissue was negative in the 147 cases examined. However, a significant contingency coefficient between low-risk HPV infection and elevated risk of chromosome aberration was found (φ = V = 0.15, P =.050). CONCLUSION: The infection rate of 24.6% in women without clinical symptoms of HPV infection was high, but there seemed to be no virus transmission to the placenta in women with subclinical infections. Low-risk cervical HPV infection might be associated with a slightly higher risk of abnormal fetal karyotype.     

乙型肝炎病毒宫内感染机理的研究

目的　探讨乙型肝炎病毒 (HBV)宫内感染的可能机理。方法　应用PCR技术检测 5 9例乙型肝炎病毒表面抗原 (HBsAg)阳性孕妇的羊水、阴道分泌物及其新生儿脐血清中HBVDNA(研究组 ) ,10例乙型肝炎病毒标志物 (HBVM )阴性的正常孕妇及其新生儿为对照组。采用免疫组化ABC染色法检测两组孕妇胎盘组织中的HBsAg及乙型肝炎核心抗原 (HBcAg)的阳性率。 结果　 ( 1)研究组孕妇的羊水、阴道分泌物、新生儿脐血清中HBVDNA阳性率分别为 4 7 5 % ( 2 8/ 5 9)、5 2 5 % ( 31/5 9)、4 5 8% ( 2 7/ 5 9) ;对照组孕妇的羊水、阴道分泌物、新生儿脐血清中均未检出HBVDNA。 ( 2 )研究组孕妇胎盘组织中HBsAg及HBcAg的阳性率 ,呈现出由蜕膜细胞 ( 76 3%及 5 9 3% )、滋养层细胞 ( 72 9%及 5 5 9% )、绒毛间质细胞 ( 6 2 7%及 5 0 8% )至绒毛毛细血管内皮细胞 ( 5 2 5 %及 4 4 1% )依次递减的趋势 ;但其中有 4例孕妇胎盘组织中HBsAg及HBcAg的分布与上述特点相反。研究组孕妇有 32例羊膜细胞中检出HBsAg及HBcAg。对照组孕妇胎盘组织中的HBsAg及HBcAg检出率为零。结论　孕妇血中HBV主要是通过感染胎盘导致胎儿感染 ;但也可能存在胎盘以外的感染途径。