ROS在LPS下调鼠胎盘pxr等基因表达中的作用

目的研究活性氧(ROS)在细菌脂多糖(LPS)下调小鼠胎盘孕烷X受体(pxr)及其靶基因细胞色素P-4503a11(cyp3 a11)和多药耐药基因1a(mdr1 a)表达中的作用。方法小鼠妊娠第17天分别注射不同剂量LPS(0.1~0.5mg/kg,ip);LPS PBN组在注射LPS(0.2 mg/kg,ip)前30 min和后3 h给予2-苯叔丁基硝酮(PBN);LPS NAC组在注射LPS(0.2 mg/kg,ip)前30 min和后3 h给予N-乙酰半胱氨酸(NAC);对照组给予等容量生理盐水或PBN/NAC。孕鼠分别于LPS处理后6和12 h处死。结果LPS显著下调小鼠胎盘pxr,cyp3 a11和mdr1 amRNA表达,进一步研究发现,妊娠晚期给予LPS后,胎盘组织MDA水平明显升高且GSH含量显著降低。PBN和NAC处理显著抑制LPS对胎盘pxr,cyp3 a11和mdr1 amRNA表达的下调作用,且显著对抗LPS引起的氧化应激。结论LPS下调小鼠胎盘pxr、cyp3 a11和mdr1 amRNA表达;ROS至少部分参与了LPS对小鼠胎盘pxrc、yp3 a11和mdr1 amRNA表达的下调作用。     

Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes

OBJECTIVE: The purpose of this study was to determine whether abnormal placentation (defined as the failure of physiologic transformation of spiral arteries) is present in patients with preterm labor and intact membranes who delivered a preterm neonate. STUDY DESIGN: A cross-sectional study was conducted to examine the histopathologic findings in the placental bed and placenta of patients with preterm labor and intact membranes (n=27), preeclampsia (n=43), and healthy pregnant women at term (n=103). Immunohistochemistry studies with cytokeratin 7 and periodic acid-Schiff were used to detect trophoblast and fibrinoid, respectively, and diagnose the failure of physiologic transformation of the spiral arteries. RESULTS: The mean percentage of spiral arteries with failure of physiologic transformation in the myometrium was significantly higher in patients with preterm labor and preeclampsia than in normal pregnant women at term (P=.0004 and P<.0001, respectively). Similar findings were observed in the decidual segment of spiral arteries within the placental bed (P=.001 and P<.0001). In contrast, the mean percentage of the spiral arteries with failure of physiologic transformation in the decidua of the basal plate was not significantly different between patients with preterm labor and normal pregnant women (P=.17). CONCLUSION: Failure of physiologic transformation of the spiral arteries in the myometrial and decidual segments of the placental bed is frequent in patients with preterm labor and intact membranes.     

宫内缺氧胎盘血管合胞体细胞膜(VSM)的形态计量及其意义

应用图像分析仪, 对56 例胎儿宫内缺氧胎盘及8 例正常胎盘中的气体交换结构—血管合胞体细胞膜(VSM) 进行了形态计量测试, 并对其中8 例缺氧胎盘及4 例正常胎盘的超微结构作了观测。结果显示: 缺氧组VSM 表面积密度较正常组显著减少; VSM 表面积在绒毛表面积中所占比例减少; VSM 滋养层下基底膜增厚; VSM 厚度增加( P< 0-01) , 并且宫内缺氧并发胎儿受损病例的VSM 总表面积明显低于生长正常胎儿。上述结果证实, VSM 的表面积减少、滋养层下基底膜增厚及VSM 厚度增加, 是宫内缺氧, 影响胎儿生长发育的病理形态学基础     

EMBOLISM OF FETAL BRAIN TISSUE TO THE LUNGS AND THE PLACENTA

We describe a case of a 19-year-old G1P0 woman with an unremarkable prenatal course who presented at term in labor. Fetal bradycardia developed and forceps were used to deliver a male infant, who was born with Apgar scores of 0 and 0 and could not be resuscitated. Examination at autopsy revealed no gross evidence of trauma, but on microscopic examination of the lungs and the placenta, multiple fetal vessels contained emboli consisting of fragments of fetal cerebellar cortex. Previously reported cases of this rare phenomenon are reviewed and the pathogenesis is discussed.     

Monozygotic Twins Concordant for Congenital Neuroblastoma: Case Report and Review of the Literature

To date, five sets of monozygotic twins concordant for neuroblastoma have appeared in the literature. Review of the clinical information available for these cases suggests that they represent congenital, versus acquired, diseases in both twins from each twin pair. The question arises, then, whether some or all sets of twins represent simultaneous-onset malignancy of both twins within a twin pair or whether metastasis via placental anastomoses from one twin with congenital disease to the cotwin occurs. This report includes a sixth set of monozygotic twins concordant for congenital neuroblastoma. From analysis of the clinical data from all cases, it appears that two of six twin pairs may represent simultaneous-onset tumors in each twin from a twin pair, and two of the remaining four twin pairs, including the present case, may represent placental metastases from one twin with congenital neuroblastoma to the other. In the remaining two twin pairs insufficient data are available upon which to draw any conclusions. Now that molecular and genetic methodology is available to characterize neuroblastomas, these techniques may be utilized in future cases of monozygotic twins concordant for congenital neuroblastoma, to help clarify whether the neoplasms represent simultaneous primary tumors versus metastatic spread from one twin to another.     

Preeclampsia: an imbalance in placental prostacyclin and thromboxane production

Preeclampsia is characterized by increased vasoconstriction frequently associated with increased platelet aggregation, reduced uteroplacental blood flow, and premature delivery. Because prostacyclin antagonizes the vasoconstrictor, platelet-aggregating, and uterine-activating actions of thromboxane, we considered the hypothesis that placental production of thromboxane was increased coincident with decreased production of prostacyclin in preeclampsia. Fresh human term placentas were obtained immediately after delivery from 11 normal and 10 preeclamptic pregnancies (blood pressure greater than or equal to 140/90 mm Hg, urinary protein greater than 0.3 gm/24 hr). Tissues (350 mg) were incubated sterilely in 6 ml of Dulbecco's Modified Eagle's Medium for 48 hours at 37 degrees C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 8, 20, 32, and 48 hours and analyzed for thromboxane by radioimmunoassay of its stable metabolite, thromboxane B2, and for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto prostaglandin F1 alpha. The production of thromboxane was significantly increased in preeclamptic versus normal placental tissue (22.9 +/- 4.7 versus 6.3 +/- 1.5 pg/mg/hr, mean +/- SE, p less than 0.01), whereas the production of prostacyclin was significantly decreased (3.0 +/- 0.3 versus 6.7 +/- 0.5 pg/mg/hr, p less than 0.001). In both normal and preeclamptic placentas, the production rates of thromboxane and prostacyclin were inhibited by indomethacin (5 mumol/L) and not affected (p greater than 0.50) by arachidonic acid (100 mumol/L). Therefore, during normal pregnancy, the placenta produces equivalent amounts of thromboxane and prostacyclin, so that their biologic actions on vascular tone, platelet aggregation, and uterine activity will be balanced. In preeclamptic pregnancy, however, the placenta produces seven times more thromboxane than prostacyclin.     

Study of interferon production during pregnancy in mice and antiviral activity in the placenta

Although the mortality rate after herpes simplex virus type 2 inoculation was not significantly different between pregnant mice and nonpregnant mice, systemic interferon production was very high during late pregnancy compared with that in nonpregnant mice. Antiviral activity was detected in placentas from all noninfected pregnant mice (80 to 320 U/ml in 20% suspension). The antiviral activity had a broad spectrum and was also effective in the cells of other species; an antiviral effect was shown even if the cells were treated after challenge with a virus. In addition, this activity was not inactivated by antimouse interferon-neutralizing antisera. The molecular weight of this placental antiviral substance was estimated to be 200,000 to 450,000 daltons by gel filtration, and it was inactivated by heat, acid, and trypsin. Noninterferon antiviral activity (40 to 80 U/ml) was also detected in more than half the sera (61.5%) of noninfected mice in late pregnancy.     

Abnormal expression of HLA-DR antigen in the placenta of a patient with pemphigoid gestationis

The villous stroma and fetal endothelium in chorionic villi adjacent to maternal decidua in a placenta of a woman suffering from pemphigoid gestationis were found to have abnormal expression of HLA-DR antigen. This aberrant DR expression may be a reflection of an immune attack on the placenta.     

Stromal cell-derived factor-1 (SDF-1) signalling regulates human placental trophoblast cell survival

Stromal cell-derived factor-1 (SDF-1 or CXCL12) is the physiologic ligand for the chemokine receptor CXCR4. CXCR4-mediated signalling regulates cell migration and apoptosis in certain haematopoietic and neuronal cells. Using gene profiling, we determined that CXCR4 is the only chemokine receptor for which mRNA expression is regulated during trophoblast differentiation in vitro. Based on the known effects of CXCR4 ligation, we hypothesized that CXCR4 activation may regulate placental trophoblast cell survival (i.e. protection from apoptosis), an important mechanism for the establishment and maintenance of the uteroplacental barrier. Human cytotrophoblasts (CTBs) were cultured in defined media and treated with graded doses of SDF-1 (10-100 ng/ml) or with an anti-CXCR4 neutralizing antibody. Exposure to anti-CXCR4 antibody reduced CTB cell numbers by 25-40%. Treatment with SDF-1 decreased the proportions of apoptotic terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick-end labelling(+) cells (apoptotic index [AI] of 2.79+/-0.61% [control] versus 1.88+/-0.56% [SDF-1]; P<0.05) and caspase-activated cells (AI of 7.95+/-2.49% [control] versus 3.81+/-1.49% [SDF-1]; P<0.05). We determined that SDF-1 also activated the triple MAP Kinase isoforms ERK1/2 and p38 in trophoblasts. Immunocytochemistry confirmed SDF-1-induced nuclear translocation of phosphorylated ERK1/2. Blocking of ERK1/2 signalling with the specific inhibitor PD98059 reversed SDF-1-mediated inhibition of apoptosis (AI of 1.65+/-0.34 [SDF-1] versus 3.50+/-0.5 [SDF-1 + PD98059]; P<0.05), suggesting that SDF-1 acts through this pathway as a trophoblast survival factor. These results indicate that SDF-1/CXCR4 signalling stimulates anti-apoptotic pathways in cultured trophoblasts. This chemotactic ligand/receptor system may promote trophoblast survival during pregnancy. Alterations in SDF-1 and/or CXCR4 expression or function may be associated with specific pregnancy disorders.     

Histologic distribution and biochemical properties of alpha 1-microglobulin in human placenta

PROBLEM: The embryo is protected from immunologic rejection by the mother, possibly accomplished by immunosuppressive molecules located in the placenta. We investigated the distribution and biochemical properties in placenta of the immunosuppressive plasma protein alpha 1-microglobulin. METHOD OF STUDY: Placental alpha 1-microglobulin was investigated by immunohistochemistry and, after extraction, by electrophoresis, immunoblotting and radioimmunoassay. RESULTS: alpha 1-Microglobulin staining was observed in the intervillous fibrin and in syncytiotrophoblasts, especially at sites with syncytial injury. Strongly stained single cells in the intervillous spaces and variably stained intravillous histiocytes were noted. Solubilization of the placenta-matrix fraction and placenta membrane fraction released predominantly the free form of alpha 1-microglobulin, but, additionally, an apparently truncated form from the placenta-membrane fraction. The soluble fraction of placenta contained two novel alpha 1-microglobulin complexes. CONCLUSIONS: The biochemical analysis indicates the presence in placenta of alpha 1-microglobulin forms not found in blood. The histochemical analysis supports the possibility that alpha 1-microglobulin may function as a local immunoregulator in the placenta.