妊娠滋养细胞疾病的发病机制研究进展

人类滋养细胞是有异于体细胞的特殊细胞,具有独特的分化特点和生物学特性。妊娠滋养细胞疾病的发生、发展更是多因素参与、极其复杂的病理过程。现代医学研究对该疾病的发生机理有进一步的认识。现就滋养细胞分化和分子生物学特点进行综述。     

妊娠合并滋养细胞疾病的诊治进展

<正>妊娠滋养细胞疾病(gestational trophoblastic disease,GTD)是一组起源于胎盘妊娠滋养细胞、多与妊娠相关的疾病,根据组织学类型可将其分为葡萄胎、侵蚀性葡萄胎、绒癌、胎盘部位滋养细胞肿瘤(placental site trophoblastic tumor, PSTT)和上皮样滋养细胞肿瘤(epithelioid trophoblastic tumor,ETT)。其中侵蚀性葡萄     

Fas及FasL在妊娠滋养细胞疾病中的表达及意义

目的 探讨Fas及FasL在妊娠滋养细胞疾病中的表达及意义.方法 应用免疫组化方法分别检测Fas及FasL蛋白在正常滋养细胞(40例)、完全性葡萄胎(36例)、侵蚀性葡萄胎(15例)、绒毛膜癌(11例)中的表达.结果 Fas在正常滋养细胞组、完全性葡萄胎组、侵蚀性葡萄胎组和绒毛膜癌的阳性表达率分别为95.0%、88.9%、46.7%和36.4%.Fas随着妊娠滋养细胞疾病的进展阳性率逐渐降低.正常滋养细胞组分别与侵蚀性葡萄胎组及绒毛膜癌组比较有显著性差异(χ2=14.036,P=0.000;χ2=16.575,P=0.000),完全性葡萄胎组与侵蚀性葡萄胎组和绒毛膜癌组比较有显著性差异(χ2=8.275,P=0.004;χ2=10.202,P=0.001),而正常滋养细胞组与完全性葡萄胎组、侵蚀性葡萄胎与绒毛膜癌组比较无显著性差异(χ2=0.314,P=0.575;χ2=0.015,P=0.902).FasL在正常滋养细胞组、完全性葡萄胎组、侵蚀性葡萄胎组和绒毛膜癌组的阳性表达率分别为17.5%、44.4%、53.3%和81.8%.FasL随着妊娠滋养细胞疾病的进展阳性率逐渐增高.正常滋养细胞组分别与完全性葡萄胎组、侵蚀性葡萄胎组及绒毛膜癌组比较有显著性差异(χ2=6.518,P=0.035;χ2=5.371,P=0.005;χ2=13.724,P=0.000),完全性葡萄胎组与绒毛膜癌组比较有显著性差异(χ2=4.727,P=0.030),完全性葡萄胎组与侵蚀性葡萄胎组、侵蚀性葡萄胎与绒毛膜癌组比较无显著性差异(χ2=0.336,P=0.562;χ2=1.191,P=0.275).Fas与FasL表达在各组之间均呈负相关.结论 Fas的低表达和FasL的高表达降低了妊娠滋养细胞凋亡,可能是妊娠滋养细胞疾病的发病机制之一.Fas和FasL的表达在各组之间均呈负相关提示二者在妊娠滋养细胞疾病进展中可能相互影响,共同作用.     

hCG试验在妊娠滋养细胞疾病诊疗中的困惑

血清人绒毛膜促性腺激素试验是临床最常用的妊娠及与妊娠相关疾病的血清诊断试验.尤其在妊娠滋养细胞疾病中,人绒毛膜促性腺激素试验对于诊断,治疗和随访有着重要的指导作用.但是随着对人绒毛膜促性腺激素分子认识的加深,仅由实验室测定结果指导医生决定诊断和治疗的局限性逐渐体现.近年陆续出现有关假阳性及持续低水平人绒毛膜促性腺激素导致不必要治疗的报道,由此引起了一些与妊娠滋养细胞疾病诊断和治疗相关的概念的重新审视和讨论,现予以综述.     

The c-erbB-related oncoproteins in normal placenta and in gestational trophoblastic diseases (in vitro study)]

In this study the expression of epidermal growth factor receptor (EGFR) and c-erbB-2, c-erbB-3 and c-erbB-4 oncogenes were investigated in gestational trophoblastic diseases and normal first trimester placenta. Furthermore, the possibility that macrophage (IL-1 alpha, IL-1 beta, TNF) and lymphocyte (IL-2, gamma-IFN, GM-CSF) cytokines effects are mediated by changes in EGFR expression were studied. Paraffin sections of 16 cases of partial mole, 25 cases of complete mole, 10 cases of gestational choriocarcinoma and 11 cases of therapeutic abortion were studied immunohistochemically for EGFR, c-erbB-2, c-erbB-3 and c-erbB-4 proteins. The presence of EGFR mRNA was studied using in situ hybridization. JEG-3 human choriocarcinoma cells were incubated with varying concentrations of interleukin 1-alpha, interleukin 1-beta, interleukin 2, gamma-interferon, granulocyte-macrophage colony stimulating factor and tumor necrosis factor-alpha, and the expression of EGFR was measured by radioimmunoassay using a murine monoclonal antibody with specificity for EGFR. Staining for EGFR was detected immunohistochemically in all cell type in gestational trophoblastic diseases and normal placenta. The levels of expression of EGFR in choriocarcinoma and syncytiotrophoblasts and cytotrophoblasts in complete mole were significantly greater than those in syncytiotrophoblasts and cytotrophoblasts in both normal placenta and partial mole (p < 0.01, p < 0.01). The immunoreactivity of c-erbB-2 was significantly stronger in choriocarcinoma and extravillous trophoblast in complete mole than that in extravillous trophoblast in partial mole and normal placenta (p < 0.02, p < 0.01, respectively). Strong immunostaining for EGFR (p = 0.02) and c-erbB-3 (p < 0.01) in extravillous trophoblasts of complete mole was found to be significantly correlated with the development of persistent postmolar gestational trophoblastic tumor. Macrophage-derived cytokines IL-1 alpha, IL-1 beta and TNF significantly suppressed cell growth; this was associated with a significant increase in EGFR expression. The lymphocyte (IL-2, gamma-IFN, GM-CSF) cytokines had no significant effect on either EGFR expression or cell growth. These findings support the concept that cytokines may act as paracrine mediators of autocrine processes involved in choriocarcinoma cell growth regulation by modulating growth factor receptor expression. The EGFR-related family of oncogenes may be important in the pathogenesis and prognosis of gestational trophoblastic diseases.     

妊娠期高尿酸血症

血清尿酸(SUA)是有核细胞代谢的终产物,生理浓度的SUA对人体具有积极的作用。随着我国生活水平提高,生活方式的改变,高尿酸血症(HUA)发病率呈上升趋势,导致痛风、高血压、心血管疾病及肾脏病发病率上升。生理情况下,尿酸的生成和排泄相对稳定。在早孕期,尿酸排泄增加,SUA浓度较孕前下降;中、晚孕期由于胎儿通过羊水排泄尿酸增加,肾脏对于尿酸的清除能力降低,孕妇内环境和饮食的改变,SUA浓度逐渐增高。妊娠期SUA异常升高,常与合并的妊娠相关疾病有关,如妊娠期高血压疾病、妊娠期糖尿病(GDM)等,3者相互影响。此外,妊娠期HUA可影响胎儿生长发育,较高浓度SUA可以作为早期诊断青少年抑郁症的生物学标志物,这可能与HUA导致脑细胞内神经元DNA氧化损伤有关。妊娠期HUA的诊断应基于妊娠期SUA的动态变化,而不是单纯依照成年人HUA的诊断标准进行判断。目前临床采用的降低尿酸浓度、促进尿酸排泄和镇痛的药物,对于HUA孕妇及其胎儿均具有一定风险。因此,适当碱化尿液、多饮水、促排尿、低嘌呤饮食、控制体重、禁烟、限酒等手段,对于HUA孕妇围生期是可行、安全的预防和治疗措施。     

Gestational Trophoblastic Neoplasia

The chorionic gonadotropin titer now makes it possible to identify early those postmolar patients who are likely to progress to choriocarcinoma, thereby opening the way to definitive treatment of this highly lethal condition. Complete and sustained remission can now be achieved in 90% of patients in whom appropriate chemotherapy is begun within four months of disease onset, and in 75% of all treated cases.     

Cohort Study of Maternal Gestational Weight Gain,Gestational Diabetes,and Childhood Asthma

Data on the association of maternal gestational weight gain (GWG) and gestational diabetes mellitus (GDM) with childhood asthma are limited and inconsistent. We aimed to investigate these associations in a U.S. pre-birth cohort. Analyses included 16,351 mother–child pairs enrolled in the Massachusetts General Hospital Maternal-Child Cohort (1998–2010). Data were obtained by linking electronic health records for prenatal visits/delivery to determine BMI, GWG, and GDM (National Diabetes Data Group criteria) and to determine asthma incidence and allergies (atopic dermatitis or allergic rhinitis) for children. The associations of prenatal exposures with asthma were evaluated using logistic regression adjusted for maternal characteristics. A total of 2306 children (14%) developed asthma by age 5 years. Overall, no association was found between GWG and asthma. GDM was positively associated with offspring asthma (OR 1.46, 95% CI 1.14–1.88). Associations between GDM and asthma were observed only among mothers with early pregnancy BMI between 20 and 24.9 kg/m² (OR 2.31, CI 1.46–3.65, p-interaction 0.02). We report novel findings on the impact of prenatal exposures on asthma, including increased risk among mothers with GDM, particularly those with a normal BMI. These findings support the strengthening of interventions targeted toward a healthier pregnancy, which may also be helpful for childhood asthma prevention.