Placenta growth factor: potential role in pregnancy

PROBLEM: In spite of the known requirement for adequate vascularity during placentation, little is known regarding the regulation of angiogenic growth factor production by trophoblast. Placenta growth factor (PIGF) is a recently discovered angiogenic growth factor whose expression is relatively limited to trophoblast. METHOD OF STUDY: Current literature of PIGF was reviewed, with emphasis on its expression, regulation, role in angiogenesis, and potential function(s) at the maternal-fetal interface. RESULTS: PIGF is abundantly expressed by trophoblast, which implies that it could act in a paracrine manner to modulate vascular development, stability, and/or function within the decidua and placental villi. In addition, expression of the PIGF receptor, fms-like tyrosine kinase (flt-1) receptor, on trophoblast raises the potential for an autocrine role of PIGF in regulating trophoblast growth and/or function. CONCLUSIONS: The potential for PIGF to influence both vascular endothelial cells and trophoblast suggests that aberrant trophoblast production of PIGF could compromise cellular function during gestation and contribute to the vascular and placental pathologies noted in many obstetric complications.     

子痫前期患者白细胞介素-8和胎盘生长因子的表达及其意义

目的通过检测子痫前期患者羊水中白细胞介素-8（IL-8）和胎盘组织中胎盘生长因子（PLGF）的水平．以探讨IL-8和PLGF在子痫前期发病中的作用。方法采用酶联免疫吸附法和免疫组化法分别测定20例轻度子痫前期患者,22例重度子痫前期患者和30例正常妊娠妇女（对照组）的羊水中IL-8和胎盘组织中的PLGF的表达。结果子痫前期轻度组及重度组羊水IL-8均高于对照组,重度组羊水IL-8显著高于轻度组,差异均有统计学意义（P〈0．01）。子痫前期轻度组及重度组胎盘组织中PLGF表达量均低于对照组（P〈0．01）,而重度组低于轻度组（P〈0．01）。子痫前期轻、重度组及对照组胎盘组织中PLGF表达量与羊水IL-8水平均呈高度负相关（P〈0．01）。结论子痫前期患者羊水中IL-8增高,而胎盘组织中PLGF表达下降,可能与子痫前期的发生、发展有关。     

超常胎盘部位的病理形态与免疫组化研究

目的：探讨超常胎盘部位（ＥＰＳ） 的病理形态与免疫组化特征,提出鉴别诊断要点。方法：对１７ 例经病理检查诊断为ＥＰＳ的病例进行病理学形态观察,采用免疫组化方法标记滋养细胞ＨＣＧ、ＨＰＬ、ＥＭＡ、ＰＲＬ、ＰＬＡＰ、Ｖｉｍ 、ａｃｔｉｎ、ｃｅｒｂＢ２ 和ｃｍｙｃ。结果：ＥＰＳ组织学特征为以中间型为主的滋养细胞向蜕膜及平滑肌浸润,不破坏原有组织结构,并保留部分胎盘床特点。免疫组化标记ＨＰＬ、ＥＭＡ呈阳性或强阳性,ＨＣＧ多为弱阳性,其他多为阴性。结论：ＥＰＳ属于中间型滋养细胞为主的妊娠滋养细胞疾病。鉴别诊断应结合组织学、免疫组化及临床表现综合判断。     

Localisation of Placenta Growth Factor (PlGF) in Human Term Placenta

Abstract

Placenta growth factor (PlGF) is a growth factor which belongs to the vascular endothelial growth factor (VEGF) family and is known to bind to the fms-like tyrosine kinase receptor (flt-1). Using Western blot analysis a 50 kDa band was identified in placental protein extract which corresponded to PlGF homodimer. Immunoreactive PlGF was localised to the vasculosyncytial membrane and in the media of large blood vessels of the placental villi, while staining within the mesenchyme was weak and diffuse. There was moderate staining for PlGF in discrete cells in the chorion and no staining in the epithelial layer of the amnion. The maternal decidual cells showed strong staining for PlGF immunoreactive protein. PlGF mRNA was predominantly expressed by the vasculosyncytial membrane of villous trophoblast, whilst there was no apparent expression of PlGF mRNA within the villous mesenchyme. These results suggest that PlGF may be an important paracrine factor for vascular endothelial cells in placental angiogenesis and an autocrine mediator of trophoblast function.     

Benign placental mass with fetal growth retardation in a bull mastiff

A 4-year-old bull mastiff presented due to premature labour. The referring veterinarian elected to perform a caesarian delivery and at the time of surgery a 4 × 4 × 2 cm round, smooth, red to tan, lobulated soft mass was identified attached to the allantoic surface of the zonary placenta of one pup. Microscopically, this mass was composed of loosely arranged confluent undulating cords of polygonal to columnar epithelioid cells separated by a fine fibrovascular stroma resembling the placental labyrinth. The labyrinthine structure and epithelioid nature of the cells suggested that the mass was of trophoblastic origin. Due to the non-invasive nature of the mass and relatively low mitotic activity, this proliferative trophoblastic mass was considered to be benign. The absence of morphological features supporting malignant behaviour and the recapitulation of the normal labyrinthine architecture led to the diagnosis of a trophoblastic hamartoma. To the authors’ knowledge this is the first report of a placental hamartoma in the dog.     

Expression of insulin-like growth factor in the placenta of intrauterine growth-retarded human fetuses

Many cases of intrauterine growth retardation (IUGR) are the result of placental and fetal tissue insufficiency. Insulin-like growth factor-I (IGF-I) is known to play a role in placental and fetal growth. An immunocytochemical study was performed to localize IGF-I peptides in human placenta and umbilical cords of normal (n = 3) and IUGR (n = 3) fetuses. The peripartum fetal conditions were evaluated as well. Immunoreactive IGF-I was detected in the cytotrophoblast, syncytiotrophoblast, amnion, endothelial cells of fetal capillaries and in the decidua in both normal and IUGR placental tissue. A more robust immunostaining and increased numbers of positively stained cells were found in the decidua of IUGR placenta (p < 0.001). Intense immunostaining was also found in endothelial cells, smooth muscle cells and fibroblasts of the umbilical vein. IGF-I immunoreactivity was also present in stroma (Hofbauer cells and/or fibroblasts) of IUGR villi. Our results indicate that expression of IGF-I is high in specific sites in placenta and umbilical cords, which indicates a paracrine and/or endocrine function. The increased expression of IGF-I in placenta of IUGR fetuses indicates its involvement in restoring normal growth by means of a positive feed-back mechanism.     

Interleukin-8 stimulates placental prostacyclin production in preeclampsia

PROBLEM: Our purpose was to determine placental interleukin (IL)-8 production and its correlation with the prostacyclin production in normal and preeclamptic pregnancies and to evaluate the beneficial effect of IL-8 on prostacyclin production. METHOD OF STUDY: We determined 1) the in vitro production of IL-8 and prostacyclin by placental villous tissues from normal and preeclamptic pregnancies and 2) the production of prostacyclin by villous tissues from preeclampsia treated with recombinant human IL-8 (rhIL-8). IL-8 levels were measured by enzyme-linked immunosorbent assay and prostacyclin by radioimmunoassay of 6-keto PGF1alpha, the stable metabolite of prostacyclin. RESULTS: 1) Placental production of IL-8 and 6-keto PGF1alpha were significantly less in preeclampsia than in normal pregnancies, P<0.05. 2) Placental production of 6-keto PGF1alpha and IL-8 was significantly correlated in preeclampsia, P<0.01. 3) Placental tissues treated with IL-8 exhibited a concentration-dependent increase in 6-keto PGF1alpha production. CONCLUSIONS: Placental tissues from preeclampsia produce significantly less IL-8 than tissues from normal pregnancies, which correlates with decreased prostacyclin production. IL-8 improves placental prostacyclin production in preeclampsia.     

超常胎盘部位临床病理及免疫组化研究

目的：研究超常胎盘部位９ＥＰＳ）的病理特点与临床表现的关系。方法：应用免疫组化ＡＢＣ法对１８例ＥＰＳ病变进行研究，并结合临床表现进行病理分析。结果：ＥＰＳ是中间型滋养细胞在胎盘部位非破坏性的浸润肌层和血管壁，而不形成肿块，胎盘泌乳素（ＨＰＬＣ）和ＣＫ强阳性或阳性，两者细胞定位相同。ＨＣＧ阳性或弱阳性或弱阳性，与ＨＰＬ定位一致或不一致。部分病例ＣＥＡ少量细胞阳性。患者可表现ＨＣＧ下降缓慢或产后出血。     

宫内发育迟缓大鼠血清胰岛素样生长因子Ⅰ、Ⅱ、BP3的变化及L-精氨酸的保护作用

目的通过L-精氨酸孕期干预后大鼠血清胰岛素样生长因子-Ⅰ、Ⅱ及结合蛋白3水平的变化,探讨L-精氨酸的保护作用及其机制。方法采用被动吸烟法造大鼠IUGR模型,孕鼠随机分为4组:对照组、模型组、L-精氨酸小剂量和大剂量防治组,每组9只。孕21d剖宫取胎,测量胎鼠体重。应用酶联免疫吸附法检测各组大鼠血清IGF-Ⅰ、IGF-Ⅱ及IG-FBP-3水平。结果对照组、模型组与小、大剂量L-精氨酸防治组IUGR发生率分别为3.92%,54.95%,5.55%和9.09%。模型组大鼠血清IGF-Ⅰ、IGF-Ⅱ水平较对照组明显降低(P<0.01),小剂量和大剂量L-精氨酸防治组与模型组相比,IGF-Ⅰ、IGF-Ⅱ水平明显增高(P<0.01)。模型组大鼠血清IGFBP-3水平较对照组明显增高(P<0.01),小剂量和大剂量L-精氨酸防治组与模型组相比,IGFBP-3水平明显降低(P<0.01),与对照组亦有明显差异(P<0.01)。结论L-精氨酸可增高被动吸烟致宫内发育迟缓大鼠血清胰岛素样生长因子-Ⅰ、Ⅱ的水平,降低胰岛素样生长因子结合蛋白3的水平,从而促进胎鼠发育,防治IUGR的发生。     

Correlation between tumor vascularity and clinical findings in patients with pituitary adenomas

Angiogenesis generally plays an essential role in tumor growth and metastasis, and also influences the response to treatment in human malignant solid tumors. Even in nonmalignant tumors, angiogenesis is essential for tumor growth and invasion. In order to define the relationship between tumor vascularity and the clinical course in patients with pituitary adenomas, we quantified the vascularity in 47 pituitary adenomas and in 6 normal anterior pituitary glands obtained at autopsy using a computed image-analyzing system. We estimated two parameters, the vascular number and the area as the vascularity. Additionally, we calculated mean individual vessel size using the above two parameters. The relationships of tumor vascularity to clinical, endocrinological and histological findings was assessed. Factors considered included patient age and gender, preoperative medication, histological type, concentration of each hypersecreted pituitary hormone, maximum tumor size, cavernous sinus invasion, intratumoral hemorrhage, and immunohistological results of localization of vascular endothelial growth factor (VEGF). Vascularity was significantly higher in normal glands than in pituitary adenomas. However, there were no significant correlations between tumor vascularity and other clinical, endocrinological, or histological parameters, suggesting that increased angiogenesis is not essential for pituitary adenoma growth or invasiveness.     

Vascular endothelial growth factor, epidermal growth factor and fibroblast growth factor-4 and -10 stimulate trophoblast plasminogen activator system and metalloproteinase-9

Trophoblast invasion, accompanied by degradation of extracellular matrix, is crucial to normal pregnancy development, whereas shallow placental invasion and implantation likely plays a role in the subsequent development of pre-eclampsia. The growth factors vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and fibroblast growth factor (FGF) are placental growth factors that activate degradation of extracellular matrix. We determined the effect of VEGF, EGF, FGF-2, FGF-4 and FGF-10 on the plasminogen activator system of first trimester cytotrophoblasts cultured in vitro. We studied the activity of urokinase plasminogen activator (uPA), its inhibitor plasminogen activator inhibitor-1 (PAI-1), and 92 kDa gelatinase-B (matrix metalloproteinase-9, MMP-9), using protein gel and reversed gel zymography. The expression pattern of FGF-4 and FGF-10 in human placental sections was determined by immunohistochemistry. FGF-4 was expressed in first trimester villi stroma, primarily in endothelial cells. FGF-10 expression was localized to first trimester extravillous trophoblasts. VEGF, EGF, FGF-4 and FGF-10, but not FGF-2, stimulate the activity of trophoblast uPA, PAI-1 and MMP-9. These results support the hypothesis that specific growth factors modulate the invasive potential of trophoblasts, and therefore may play an important role in early placental development. Our findings may contribute to the understanding of the pathophysiology of diseases associated with shallow placentation, such as pre-eclampsia.     

Pregnancy: Differential increase in the maternal serum concentrations of the placental proteins human chorionic gonadotrophin, pregnancy-specific {beta}1-glycoprotein, human placental lactogen and pregnancy-associated plasma protein-A during the first half of normal pregnancy, elucidated by means of a mathematical model

The present study was performed to compare the increase in maternalserum concentrations of four placental proteins during the firsthalf of 240 normal pregnancies. The proteins were pregnancy-associatedplasma protein-A (PAPP-A), human chorionic gonadotrophin (HCG),human placental lactogen (HPL) hormone, and pregnancy-specific1-glyco-protein (PSG), all produced by trophoblast cells. Themedian increases were observed to be very close to exponentialgrowth curves. Based on simple assumptions, these growth curvescould be explained as being solely dependent on the growth ofthe placenta. The assumptions were that the proteins were producedin the placenta at a constant rate per gram of placental cellmass and secreted into the circulation shortly after synthesis.Our investigations showed that for two of the proteins, PSGand HPL, the rate constants were, in fact, close to the reportedgrowth rate of the placenta, whereas the PAPP-A production rateconstant was significantly higher than those of the others.The production curve for HCG was very different from that ofthe other proteins. PAPP-A and HCG must therefore have morecomplicated mechanisms for regulating the production. An equationwas constructed that permitted estimation of the molar productionof the placental proteins per gram of placental cell mass perday during the first half of normal pregnancy. The value washighest for HPL and lowest for PAPP-A.     

Expression of IGR-IR and VEGF and trophoblastic proliferative activity in placentas from pregnancies complicated by IUGR

Intrauterine growth retardation (IUGR) is recognized as an important cause of low birth weight and elective preterm delivery. IUGR is associated with multiple causative factors, including placental dysfunction. The aim of this prospective study was to investigate the role of trophoblastic proliferative activity and type I insuline-like growth factor receptor (IGF-IR) and vascular endothelial growth factor (VEGF) expressions in the pathogenesis of IUGR. Immunohistochemistry using VEGF, IGF-IR, and Ki-67 antibodies was performed on formalin-fixed placental tissues of third-trimester pregnancies complicated by IUGR (n = 19) and pregnancies with appropriately grown fetuses (n = 27). In addition, histopathological examination of the placentas was performed, and histological findings were categorized into three groups: utero-placental vascular pathologies (UPVP), coagulation-related pathologies, and chronic inflammation. Statistical analysis revealed that villous trophoblastic IGF-IR immunostaining was significantly weaker in placentas with IUGR (p < 0.001), whereas trophoblastic Ki-67 proliferative index and VEGF immunoscoring did not show any significant difference. Histologically, UPVP and chronic inflammation were significant findings in placentas with IUGR (p = 0.04 and p = 0.04, respectively). In addition, placentas were significantly smaller in the IUGR group (p < 0.001). We conclude that villous trophoblastic IGF-IR expression may play a significant role in the pathogenesis of IUGR, and histopathological examination of placentas in pregnancies complicated by IUGR may yield significant findings. In contrast, based on our findings, trophoblastic proliferation and VEGF expression are unlikely to be significant parameters in the pathogenesis of IUGR.     

太原地区微量元素与妊娠合并症关系探讨

本文对太原南城正常育龄妇女526例，正常晚期妊娠30例，妊娠合并妊高征22例，宫内发育迟缓20例，生畸形儿产妇40例，采用核素激发X荧光分析法，测头哪6种微量元素并作一对比分析．结果：妊娠妇女Ca、Cr、Fe含量明显低于正常育龄妇女组，而后者的Fe、Cr也低于天津的同类报告．此外．生畸形儿及宫内发育迟缓母亲的发Zn，都低于正常育龄妇女组及晚孕组．各组Cu偏低．各组Se明显低于正常组，说明微量元素Ca、Cr、Fe、Zn、Cu、Se与妊娠关系密切．应作为围产期监测内容之一。     

子痫前期患者胎盘组织PLGF表达及血清HGF和VEGF测定

目的：探讨子痫前期患者血清肝细胞生长因子（HGF）、胎盘生长因子（PLGF）表达水平和血管内皮生长因子（VEGF）水平的变化及意义。方法：分别采用放射免疫分析、酶联免疫分析和免疫组化法测定32例子痫前期孕妇（子痫前期组）和35名正常孕妇（对照组）血清VEGF、HGF和PLGF表达水平。结果：子痫前期患者无论轻度子痫前期组和重度组血清HGF含量均显著低于对照组（P均〈0.01）;但轻度和重度组之间水平无显著性差异（P〉0.05）。胎盘中PLGF表达水平也显示轻度和重度两组均显著低于对照组（P均〈0.01）;且重度组又显著低于轻度组（P〈0.01）。血清VEGF水平轻度组显著低于对照组（P〈0.05）;重度组水平较对照组降低更为显著（P〈0.01）,且重度组显著低于轻度组（P〈0.01）。相关分析显示,HGF含量与PLGF具有显著相关性（r=0.6012,P〈0.01）;而与VEGF水平则无明显相关性（r=0.3010,P〉0.05）。结论：测定结果证实,患者血清三项标志物均参与了子痫前期的病理进程,其测定对于了解病情和预后评估有帮助。     

补肾益气活血方对宫内生长迟缓胎儿一氧化氮及脂质过氧化水平的影响

探讨补肾益气活血方对胎儿宫内生长迟缓（ＩＵＧＲ）胎盘微循环障碍的影响。方法：应用ＮＡＤＰＨ一黄递酶组织化学方法检测胎盘组织一氧化氮合酶（ＮＯＳ）活性,采用镇铜镉还原法及硫代巴比妥酸比色法（ＴＢＡ法）测定了新生儿脐血血浆亚硝酸盐／硝酸盐（ＮＯ２－／ＮＯ３－）和丙二醛（ＭＤＡ）浓度。结果：ＩＵＧＲ孕妇胎盘组织ＮＯＳ活性较正常足月妊娠明显下降,新生儿脐血ＮＯ２－／ＮＯ３－低于正常新生儿（<０．０１）,而ＭＤＡ水平高于正常（Ｐ<０．０１）,中药治疗后与正常对照组差异无显著性（Ｐ均＞０．０５）,相关性分析表明ＮＯ２－／ＮＯ３－与ＭＤＡ呈明显负相关（ｒ＝－０．６１２４,Ｐ<０．０５）。结论：脂质过氧化可能是引起ＩＵＧＲ胎盘微循环障碍的中介因子之一,补肾益气活血方促进胎儿宫内生长发育与其抗自由基损伤,增强胎盘组织一氧化氮（ＮＯ）合成和分泌有关。     

L-精氨酸治疗对胎儿宫内发育迟缓孕妇血液流变性的影响

目的 :探讨L 精氨酸 (L Arg)治疗对胎儿宫内发育迟缓 (IUGR)孕妇血液流变性的影响。方法 :选择符合入选条件的IUGR患者 6 6例 ,其中常规治疗组 35例 ,予以常规治疗 ;L Arg组 30例 ,在常规治疗的基础上加用L Arg治疗。另外 ,选择正常初产妇 31例为正常对照组。监测治疗前后孕妇血液流变学参数变化。结果 :治疗后 ,L Arg组全血低切粘度 (LBV)值较常规治疗组显著降低(P <0 .0 5)。结论 :L Arg能改善IUGR孕妇的血液流变学部分指标。