Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypevascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mecha-nism under such a hypoxic state at high altitude.     

Effect of beta2-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice

beta(2)-Glycoprotein I (beta(2)GPI) is a principal target antigen for antiphospholipid antibodies associated with recurrent pregnancy loss and fetal growth restriction in women. The significance of disrupted beta(2)GPI activity in contributing to pregnancy pathology in antiphospholipid syndrome (APS) is not clear. In this study the physiological requirement for functional beta(2)GPI in pregnancy was investigated by evaluating reproductive outcomes in beta(2)GPI null mutant (beta(2)GPI-/-) mice. beta(2)GPI-/- mice were fertile and carried viable fetuses to term. However, there was an 18% reduction in the number of viable implantation sites in beta(2)GPI-/- mice and reduced fetal weight and fetal:placental weight ratio in late gestation, suggesting compromised placental function. Placental architecture was altered in beta(2)GPI-/- implantation sites with a 24% increase in the junctional zone: labyrinthine ratio, but placentae showed no evidence of increased thrombosis in the absence of beta(2)GPI. The effect of beta(2)GPI genotype on pregnancy success after passive transfer of human and mouse antibodies reactive with beta(2)GPI was also explored. Two of five anti-beta(2)GPI antibodies induced pregnancy loss in beta(2)GPI+/+ mice but beta(2)GPI-/- mice were refractory to antibody-induced pregnancy failure. We conclude that functional beta(2)GPI is not essential for successful pregnancy in mice, but optimal placental development and fetal growth require this molecule. Together these data are consistent with pathogenic mechanisms in antiphospholipid syndrome involving both neutralization of beta(2)GPI function and beta(2)GPI-immunoglobulin complex formation.     

Pre-term birth and severe pre-eclampsia are not associated with altered expression of HLA on human trophoblasts

PROBLEM: The unusual pattern of human leukocyte antigen (HLA) expression on human trophoblasts could play an important role in successful pregnancy outcome. To determine whether alterations in HLA expression are associated with pregnancy abnormalities we have investigated expression of these antigens on chorionic and extravillous cytotrophoblasts. METHODS: Frozen tissue sections of placenta and fetal membranes were collected after pre-term spontaneous delivery, severe pre-eclampsia pre-term Caesarean section, normal term delivery and term Caesarean section. HLA expression was analyzed by immunohistochemistry. RESULTS: We did not observe differences in the expression of HLA on chorionic and extravillous cytotrophoblasts in pregnancy abnormalities. However, we noted higher expression levels of HLA class Ia molecules in amnion epithelial cells in pre-term deliveries. Furthermore, in severe pre-eclampsia the number of extravillous cytotrophoblast islands were elevated when compared with pre-term deliveries. CONCLUSIONS: No alterations in expression of HLA class Ia, HLA-G and HLA class II on human trophoblasts in pregnancy abnormalities were seen.     

Quantitative and qualitative changes in the intraepithelial lymphocyte population in the uterus of nonpregnant and pregnant sheep.

PROBLEM: Previous studies have revealed the presence of a unique population of CD45R+ granulated cells in the sheep uterine epithelium. In the present study, dramatic changes in this cell population and in the nongranulated lymphocytes in the uterine and endometrial glandular epithelium of non-cycling, cycling, pregnant, and postparturient sheep are described. In noncycling and cycling sheep, the granules in the granulated intraepithelial cells were small. From days 55 to 134 of pregnancy, the granules in these cells were large, and there was a significant increase (P < 0.01) in the proportion of this cell population in the uterine epithelium but not in the endometrial glandular epithelium located in the deeper region of the stroma. The number of these cells declined dramatically (P < 0.01) from 2 to 15 days after parturition. Both the tissue distribution and the time of activation of these cells suggests they are different from the granulated lymphocytes described in placentae of mice and man. CONCLUSIONS: It is concluded that this unique population of granulated cells is derived from lymphocytes, and that these cells become metabolically active from mid- to late-pregnancy and may play a physiological role during pregnancy or birth. In contrast, the number of nongranulated intraepithelial lymphocytes were suppressed throughout pregnancy and they probably do not play a role in pregnancy.     

血管内皮生长因子在妊高征胎盘中的表达研究

目的观察血管内皮生长因子(VEGF)在妊高征(PIH)胎盘中的表达情况.方法用免疫组织化学法,检测30例正常晚孕胎盘(对照组)和34例妊高征胎盘(妊高征组)中的VEGF表达水平,并作计算机图像分析,测定各组标本的阳性染色光度值.结果VEGF在正常晚孕胎盘和妊高征胎盘中均有表达,其分布基本一致,主要在滋养细胞、血管内皮及绒毛间质.计算机图像分析结果示,对照组VEGF阳性染色光度为0.23780±0.00434,妊高征组VEGF阳性染色光度为0.20688±0.01530,其中轻度0.22603±0.00828,中度0.20364±0.00365,重度0.19151±0.00441,妊高征组中VEGF表达明显低于对照组P＜0.01.且随妊高征病情的加重,VEGFF表达水平呈下降趋势.结论妊高征胎盘中VEGF表达水平降低可能与胎盘血管生成减少及胎盘滋养细胞侵入异常有关,在妊高征的发病中起重要作用.     

剖宫产术中大出血的原因分析与治疗

目的探讨剖宫产术中大出血的原因及治疗.方法回顾性分析39例剖宫产术中出血≥1000ml作为研究组,出血＜1 000ml,且＞500ml者作为对照组1,出血≤500ml者600例作为对照组2.结果研究组中出血首位原因主要为前置胎盘和低置胎盘,占53.85%(21/39),显著高于对照组1中的10.67%(27/253),P＜0.01.在药物控制出血失败后,11例子宫动脉结扎中8例治疗成功、29例宫腔填塞纱条中28例治疗成功,得以保留子宫,2例行子宫切除术.结论前置胎盘和低置胎盘是剖宫产术中大出血的主要原因,宫腔填塞纱条治疗剖宫产术中大出血有良好效果.     

Placental leptin correlates with intrauterine fetal growth and development

目的　探讨胎盘肥胖基因及其蛋白表达水平与脐血瘦素和胎儿宫内生长发育的关系。方法　在 4 0例产妇分娩时采集胎盘与脐血 ,采用逆转录聚合酶链反应 (RT PCR)检测胎盘肥胖基因mRNA相对表达水平 ,采用Western Blot检测胎盘肥胖基因蛋白 (瘦素leptin)表达水平 ,采用免疫组化观察胎盘肥胖基因蛋白表达位点 ,采用放射免疫法 (RIA)检测脐血瘦素水平 ,采用Ponderal指数 [PI=10 0×体重 (g) /身长 (cm) 3]估测新生儿营养状态。结果　胎盘组织肥胖基因呈现高效表达 ,在胎盘滋养层细胞浆内肥胖基因蛋白阳性表达。胎盘肥胖基因及其蛋白表达水平与胎儿宫内生长发育状态显著相关 ,13例小于胎龄儿胎盘组织leptin mRNA及其蛋白表达水平显著低于 15例适于胎龄儿 (P =0 .0 0 3和 0 .0 0 8) ,12例大于胎龄儿胎盘组织leptin mRNA及其蛋白表达水平显著高于适于胎龄儿 (P =0 .0 4和 0 .0 2 )。胎盘肥胖基因mRNA及其蛋白表达水平与脐血瘦素水平显著相关 (r =0 .39和0 .4 3,P <0 .0 5) ,与新生儿Ponderal指数 (PI)显著相关 (r=0 .66和 0 .69,P <0 .0 1)。结论　胎盘是脐血瘦素重要来源 ,胎盘瘦素可能对胎儿宫内生长发育有促进作用。     

检测孕妇血浆中的urocortin

目的：研究ｕｒｏｃｏｒｔｉｎ（促肾上腺皮质激素释放激素肽类家族新成员）是否存在于孕妇血循环中及其含量,以证实ｕｒｏｃｏｒｔｉｎ是否能在妊娠中产生并由此调节子宫－胎盘的血管张力。方法：用放射免疫测定法从受孕１６周起检测孕妇血浆中是否含有ｕｒｏｃｏｒｔｉｎ,并用凝胶层析法检测从孕妇血浆中提取的ｕｒｏｃｏｒｔｉｎ是否与人工合成的ｕｒｏｃｏｒｔｉｎ标准品一致。结果：从受孕１６周起孕妇的血浆中即可测得ｕｒｏ     

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.