胎儿生长迟缓孕妇胎盘微绒毛的体视学研究

对１２例胎儿生长迟缓及１０例正常胎儿（对照组）的盘组织进行光镜水平和电镜水平的定量观测。ＩＵＧＲ组中，胎盘正常重量指数的有６例，低重量的指数的有６例。结果：ＩＵＧＲ组胎盘重量、胎盘容积、绒毛表面积及绒毛毛细血管表面积均小于对照组，ＮＰＩ组胎盘重量、胎盘容积、绒毛表面积、绒毛毛细血管表面积、微绒行间腔表面积密度和微绒毛表面积绝驿值小于对照组及ＬＰＩ组。     

Morphometric evidence that villous development and fetoplacental angiogenesis are compromised by intrauterine growth restriction but not by pre-eclampsia

The aim of this study was to compare morphometric measures of villous development, villous capillarization, fetoplacental angiogenesis and capillary lumen remodelling in normal pregnancies with those complicated by intrauterine growth restriction (IUGR) with and without preeclampsia (PE). To this end, term placentas from control pregnancies (n = 9) and cases of IUGR alone (n = 5), PE alone (n = 5) and IUGR with PE (n = 5) provided random samples of tissue. These were fixed in formalin and Masson trichrome-stained wax sections were analysed stereologically. Overall growth of peripheral villi and fetal capillaries was assessed by estimating total volumes, surface areas and lengths. Villous capillarization was monitored using volume, surface and length densities and capillary:villus surface and length ratios. Measures of villous maturation and capillary lumen remodelling comprised mean cross-sectional areas, perimeters and shapes (perimeter(2)/area). Between-group comparisons were drawn using two-way analysis of variance. IUGR was associated with abnormal growth of villi and fetal capillaries. Reduced villous growth was not accompanied by changes in measures of villous capillarization or maturation and reduced capillary growth was not accompanied by changes in lumen calibre or shape. In contrast, PE was not associated with any main or interaction effects on placental morphometry. It is concluded that IUGR, but not PE, is associated with impoverished villous development and fetoplacental angiogenesis. The latter is due to production of fewer and/or shorter capillary segments (rather than a decrease in capillary calibre), does not affect villous capillarization and is not accompanied by luminal remodelling.     

Placental nutrient transfer capacity and fetal growth

The objective of this study was to determine whether the ability of the human placenta to transfer glucose and fatty acids is related to normal fetal growth. The intrinsic nutrient transport capacity of the placenta was measured under standardized conditions during in vitro perfusion of 30 human term placentas and related to birth weight (range 2640-4640g), birth weight centile (8th-99th), ponderal index (2.43-3.69), placental weight (418-1030g) and placental:fetal weight (0.14-0.31). There was no statistically significant change in the rate of nutrient transfer per placenta or per kg fetal weight, with birth weight, birth weight centile, ponderal index, placental weight and placental:fetal weight. There was a weak but significant relationship (P=0.020, r(2)=9 per cent) between the ratio of glucose to fatty acid transport and birth weight centile, largely due to the high ratio found in the lowest birth weight quartile where the babies are thinnest. This study provides no evidence that placental nutrient transport capacity limits fetal growth across a wide range of birth weights in normal pregnancies. It is proposed that the fetus itself may regulate placental nutrient transport in vivo via the fetal cardiac output and the rate of fetal nutrient utilization.     

Placenta and fetal growth restriction

The placenta, as the vector for all maternal-fetal oxygen and nutrient exchange, is a principal influence on birthweight. Placental weight summarizes laterally expanding growth of the chorionic disc, and villous arborization yielding the nutrient exchange surface. These different growth dimensions alter fetoplacental weight ratio and ponderal index, and thus may modify placental functional efficiency. The placenta may show a range of histopathologies, some of which are also associated with fetal growth restriction. Different fetal intrinsic abilities to compensate for gross and histo-pathology may clarify the imperfect relationships between fetal growth and both intrauterine pathology, and the long-term health risks associated with poor fetal growth.     

Confined placental mosaicism as a risk factor among newborns with fetal growth restriction

OBJECTIVE: To delineate the frequency and clinical presentation of confined placental mosaicism (CPM) among newborns with idiopathic intrauterine growth restriction (IUGR) as compared to infants with appropriate fetal growth. METHODS: 70 newborns with IUGR (birth weight < 10%) were matched by maternal age (+/-5 years) and gestational age (+/-7 days) to an equal number of infants of normal size. From both populations, placental samples underwent karyotype analysis following standard culture. RESULTS: CPM occurred significantly more often in the placentas from IUGR infants compared to controls, 11/70 (15.7%) and 1/70 (1.4%) respectively (p = 0.008). High-level tetraploidy (>20% in a primary culture) predominated among the IUGR placentas, while autosomal aneuploidy occurred only once in each population. Placental histology revealed significantly greater decidual vasculopathy, infarction, and intervillous thrombus formation in the karyotypically abnormal placentas (p = 0.03). Maternal age, gestational age at delivery, degree of growth restriction and ponderal index did not vary with the presence of CPM. CONCLUSION: CPM, and principally high-level tetraploidy, is found significantly more often among the placentas of newborns with IUGR. Infants with IUGR and CPM are clinically diverse although the placentas display pathologic changes suggestive of chronic impairment of uteroplacental function.     

The individual fetal weight/estimated placental weight ratios in monochorionic twins with selective intrauterine growth restriction

OBJECTIVES: To evaluate the individual fetal weight/estimated placental weight ratios (F/P ratio) of the two fetuses in monochorionic (MC) twins with selective intrauterine growth restriction (IUGR). MATERIAL AND METHODS: MC twin with selective IUGR was defined as an estimated fetal weight below the 10th percentile in one twin of MC pregnancy. The estimated individual placental weight was obtained by cutting the placenta along the vascular equator into two territories. A total of 15 MC twins with selective IUGR and 18 MC twins without selective IUGR were included in this study. RESULTS: The individual F/P ratio in the IUGR twin is significantly higher than that in the appropriate for gestational age (AGA) one in MC twin with selective IUGR (6.4 vs 4.0 respectively, p < 0.001). In MC twin without IUGR, the F/P ratios are not significantly different between the two fetuses (5.4 vs 5.1, respectively). CONCLUSION: The high F/P ratio in the IUGR twin in MC with selective IUGR may be due to the placental reserve phenomenon, so that a smaller placental territory may suffice to perfuse the IUGR twin. In other words, in MC twin gestations with an IUGR twin, the fetal weights are not proportional to the placental masses.     

胎儿宫内生长迟缓患者脐动脉波形异常与胎盘病理改变的关系

目的　探讨胎儿宫内生长迟缓（IUGR）患者胎儿脐动脉波形异常与胎盘重量、体积及各级绒毛血管数量的关系。方法　选择分娩前1周内,患IUGR或B超检查有胎儿脐动脉波形异常的患者40例,分为脐动脉波形异常伴IUGR10例为研究组;脐动脉波形异常不伴IUGR（AN）;脐动脉波形正常伴IUGR（NA）,脐动脉波形正常不伴IUGR（NN）各10例为对照组。用免疫组织化学SP法,检测以上各组胎盘干血管中α-平滑肌肌动蛋白（α-smoothmuscleactin,α-SMA）表达,以确定各级绒毛和各级血管,比较研究组和各对照组间胎盘重量、体积大小、各级绒毛及血管数量。结果　（1）研究组胎盘重量、体积分别为（283.40±23.82)g及（234.60±52.08)cm     

Gene expression patterns of the 11β-hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: the role of impaired feto-maternal glucocorticoid metabolism

Objective

To assess 11-β-hydroxysteroid dehydrogenase 2 (11β-HSD2) gene expression patterns in human placental samples from intrauterine growth restriction (IUGR) pregnancies using normal pregnancy as control.

Study design

We compared 11-β-HSD2 gene expression in placental samples from all IUGR pregnancies treated in our clinic between January 1, 2010 and January 1, 2011 vs. 140 normal pregnancy samples from the same study period. Clinical characteristics were also assessed and compared between the IUGR and normal pregnancy groups.

Results

Mean gestational weight gain in the IUGR group was significantly lower than in the control group. Similarly, change in body mass index (BMI) was lower. Impending intrauterine fetal asphyxia was significantly more common in the IUGR group. The 11β-HSD2 gene was underexpressed compared to controls, but this underexpression was only observed after the 33rd gestational week. Within the IUGR group, in cases of impending intrauterine fetal asphyxia the 11β-HSD2 gene was underexpressed compared to both impending asphyxia in non-IUGR cases, or IUGR without impending asphyxia.

Conclusion

Low gestational weight gain appears to predict IUGR. The 11β-HSD2 gene in IUGR is underexpressed and may result in an impaired placental barrier, decreasing protection against maternal glucocorticoids, which are thought to be prominent in fetal programming. Maternal glucocorticoid exposure resulting from an impaired placental barrier may increase the risk for cardiovascular and metobolic disorders later in adult life. In IUGR, before the 33rd gestational week, the expression of the 11β-HSD2 gene remains physiological. The underexpression of this gene after the 33rd week in impending intrauterine fetal asphyxia in IUGR points to an increased sensitivity to hypoxia when impending asphyxia is present in the late phase of IUGR pregnancies.     

Moderate maternal nutrient restriction, but not glucocorticoid administration, leads to placental morphological changes in the baboon (Papio sp.)

The aims of the present study were to describe the ontogeny of spatial relationships between placental components in baboons and to investigate alterations in these indices following (1) moderate maternal nutrient restriction and (2) administration of glucocorticoids to pregnant baboons. We investigated the effects of glucocorticoids since they have been shown to play a role in the altered fetal growth that accompanies maternal nutrient restriction. Glucocorticoids are also given to pregnant women who threaten premature labor to accelerate fetal lung maturation. A third aim was to compare our findings to those in similar conditions in human pregnancy. Volumetric placental development in the baboon was similar to that in the human, although growth of fetal capillaries was slower over the second half of gestation in baboon than in human placentas. Intervillous space (IVS) and villous star volumes were halved at the end of gestation compared to the middle of gestation, as described in the human placenta. When mothers were fed 70% of feed eaten by controls fed ad libitum, placental volumetric structure was unchanged at mid-gestation but was altered by the end of gestation when placental weight, but not fetal weight or length, was decreased. At the end of gestation villous volume and surface area, capillary surface area, and the villous isomorphic coefficient were all decreased, In contrast, IVS hydraulic diameter was increased. All parameters were similar in pregnancies with male and female fetuses, with the exception of fetal capillary volume, which was unchanged in pooled samples and those from male fetuses, but decreased in pregnancies with female fetuses. Glucocorticoid administration during the second half of gestation did not produce any changes in the measured indices of placental composition. In summary, these changes in placental structure, associated with maternal nutrient restriction, would all act to decrease placental transport of nutrients. The influence of MNR on villous capillarization depends on fetal gender.     

An image analysis technique for the investigation of variations in placental morphology in pregnancies complicated by preeclampsia with and without intrauterine growth restriction

OBJECTIVE: The purpose of this study was to use visual image analysis to observe changes in the morphology and composition of placental villi in pregnancies complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR). METHODS: Placental biopsies from nine normal pregnancies, five cases of PE, five cases of IUGR, and five cases of PE with IUGR (PE x IUGR) were randomly sampled. Formalin-fixed, wax-embedded sections were stained with hematoxylin and eosin (H&E) and subjected to image analysis. The placental areas occupied by villi, syncytiotrophoblast, and syncytial cytoplasm and nuclei were quantified. RESULTS: Significantly smaller placentas were obtained from growth-restricted pregnancies. PE, with and without IUGR, had no effect on the total area occupied by villi or intervillous space. IUGR alone showed a real and consistent reduction in villous area (56.0 +/- 2.4% vs 43.6 +/- 3.3%, P <.03). While the ratio of syncytial to villous areas were noticeably reduced in all cases of PE (0.38 +/- 0.03 vs 0.24 +/- 0.07, P <.05), this ratio remained unchanging in IUGR. Birth weight was positively correlated to both placental size and total villous area occupied. Moreover, increasingly positive relationships were recorded between both syncytiotrophoblast area and syncytiotrophoblast cytoplasm and birth weight (P <.01 and P <.001, respectively). CONCLUSION: These measurements point to impoverished villus development in idiopathic IUGR. The observed changes in PE with IUGR were more akin to PE without growth restriction than IUGR alone. This suggests that idiopathic IUGR and IUGR in PE have a separate etiology, idiopathic IUGR arising through a reduction in villous area alone, and IUGR in PE caused by changes in syncytiotrophoblast quantity, more specifically the amount of syncytiotrophoblast cytoplasm.     

Value of fetal ponderal index in predicting growth retardation

Fetal ponderal indexes were calculated by ultrasound examination and compared with the neonatal ponderal indexes in 113 pregnancies. The relationship between the fetal and neonatal ponderal indexes throughout gestation is described. The fetal ponderal index also was evaluated as a predictor of intrauterine growth retardation (IUGR) and was found to have sensitivity and specificity of 76.9 and 82%, respectively. These data suggest that the fetal ponderal index could be used to rule out the diagnosis of IUGR with reasonable accuracy (negative predictive value 96.4%).     

Development of the early human placenta: a morphometric study.

The placentae of 46 normal pregnancies artificially terminated between 6 and 15 weeks of gestation were investigated morphologically to provide trends in early villous development. Study of the specimens included phase contrast microscopic examination and histomorphometric investigation in all cases, and scanning electron microscopy in ten cases. Histomorphometric measurements included the villous barrier thickness i.e. the distance between the intervillous space and the villous capillary lumen, the trophoblastic layer thickness and the volume fraction of each villous constituents, i.e. trophoblast, stroma and capillaries. Significant negative correlations were observed between gestational age and the villous barrier and trophoblastic thickness. The data obtained were separated into two groups, embryonic (5-10 weeks) and fetal (11-15 weeks) groups, and compared. The mean barrier thickness, the mean trophoblastic thickness, the mean volume fraction for trophoblast and the sprouting-villous index were significantly greater during the embryonic period compared with the fetal period. The mean volume fraction for the stroma and for the fetal capillaries, and the mean number of capillary profiles per villous profile were significantly smaller during the embryonic period than during the fetal period. The comparison of placental histomorphometric data obtained in cases of normal early pregnancies with those observed in cases of abnormal early pregnancies could help us to elucidate the origin of anatomical and biological changes in these cases.     

Placental system A amino acid transport is reduced in pregnancies with small for gestational age (SGA) infants but not in preeclampsia with SGA infants

Preeclampsia and intrauterine growth restriction (IUGR) are both associated with abnormal remodeling of maternal spiral arteries perfusing the placental site. This would be expected to be associated with reduced fetal growth, yet only one third of infants of mothers with preeclampsia are growth restricted. Infants with IUGR have decreased concentrations of amino acids in their blood and system A amino acid transporter activity is reduced in their placentas. Since infants of preeclamptic pregnancies have increased circulating amino acids, we tested system A amino acid transport activity of placental villous fragments from pregnancies with small for gestational age (SGA) infants with and without maternal preeclampsia and from uncomplicated and preeclamptic pregnancies with normal sized infants. We confirm the reduced uptake of amino acids in SGA pregnancies without preeclampsia but report that placental amino acid uptake of SGA infants with maternal preeclampsia is not reduced and is identical to uptake by normal and preeclamptic pregnancies with normal weight infants.     

表皮生长因子及其受体与胎儿出生体重的关系

目的探讨表皮生长因子（ＥＧＦ）及其受体与胎儿出生体重的关系。方法采用酶联免疫吸附测定法对正常非孕妇女１５例（对照组）、足月正常体重儿４０例（正常体重儿组）、ＩＵＧＲ儿４０例（ＩＵＧＲ儿组）、巨大儿２５例（巨大儿组）的母血清、脐血清及羊水中ＥＧＦ浓度进行测定,同时采用免疫组化方法对以上各组胎盘及胎膜上ＥＧＦ受体（ＥＧＦＲ）进行测定。结果各组母血、脐血及羊水中ＥＧＦ浓度明显高于对照组（Ｐ＜００５）。ＩＵＧＲ儿组母血、脐血及羊水中ＥＧＦ浓度低于正常体重儿组,差异有显著性。巨大儿组母血、脐血及羊水中ＥＧＦ浓度与正常体重儿组比较,差异无显著性。在ＩＵＧＲ儿组胎盘及胎膜上ＥＧＦＲ表达明显低于正常体重儿组（Ｐ＜０．０１）,巨大儿组胎盘上ＥＧＦＲ表达高于正常体重儿组。结论ＥＧＦ及其受体与ＩＵＧＲ的发生有关,在妊娠后期测定母血及羊水中ＥＧＦ浓度,对评价胎儿的生长发育具有重要意义。     

Placental gene expression patterns of endoglin (CD105) in intrauterine growth restriction

Abstract

Objective: In this study, we describe placental gene expression patterns of endoglin in pregnancies with intrauterine growth restriction (IUGR) compared to normal pregnancies.

Methods: Placental samples were obtained from 101 pregnancies with IUGR using 140 normal pregnancy cases as control. Gene expression patterns and protein levels of the endoglin were compared between the two groups. For the gene expression analysis real-time PCR was applied, while for the estimation of placental protein level we performed Western analysis.

Results: The placental endoglin gene was significantly overexpressed in the IUGR group versus the control group (Ln2^α: 1.69). The placental endoglin protein level proved to be significantly higher in case of IUGR (endoglin/β-actin ratio: 13.8?±?2.3) versus the control cases (5.3?±?1.1). The placental gene expression as well as the protein levels of endoglin showed no significant difference between female and male newborns. Concerning the placental gene expression and protein level, no significant difference was justified between the more (0–5 percentile) and less (5–10 percentile) severe cases of IUGR.

Conclusion: Increased placental gene expression of endoglin may result in vascular dysfunction leading to chronic fetal hypoxia, which may induce VEGF-A to stimulate angiogenesis. This can be explained as feed back response to restore fetal placental circulation.     

Correlation of confined placental mosaicism with fetal intrauterine growth retardation. A case control study of placentas at delivery

OBJECTIVE: Our purpose was to determine if the frequency of confined placental mosaicism in newborns with unexplained intrauterine growth retardation (IUGR) was higher compared with infants with appropriate growth in utero and the outcome of these pregnancies. STUDY DESIGN: A total of 20 cases with unexplained IUGR and 20 cases with appropriate growth for gestational age has been studied. Amnion, chorion and villi biopsy specimens were obtained from growth-retarded cases and controls at delivery. Cord blood specimens for 48-hour lymphocyte cultures were obtained from all infants with IUGR. RESULTS: Karyotype analysis revealed confined placental mosaicism in two of 20 (10%) cases with IUGR. In one growth retarded case and one appropriate growth for gestational age case, mosaicism was also confirmed in the amnion. Cytogenetic analysis from peripheral blood of newborns showed normal karyotype in all cases. Three pregnancies in the group of fetuses with IUGR (15%) ended with fetal death compared with normal fetal surveillance of all cases from the control group. CONCLUSION: Confined placental mosaicism was detected two times more frequently from placentas of growth- retarded infants compared with those of newborns with appropriate growth. The fetal loss was significantly higher in the group of cases with IUGR compared with the control group.     

The placenta in pre-eclampsia and intrauterine growth restriction: studies on exchange surface areas, diffusion distances and villous membrane diffusive conductances

We test the null hypothesis that the morphometric diffusive conductance of the placental villous membrane does not alter in pregnancies complicated by intrauterine growth restriction (IUGR) or pre-eclampsia (PE). Placentas were collected from cases of normotensive IUGR, pure PE, PE+IUGR and from control pregnancies. Microscopical fields on formalin-fixed, trichrome-stained histological sections were randomly sampled for location and orientation. Using stereological methods, the exchange surface areas of peripheral (terminal and intermediate) villi and their fetal capillaries and the arithmetic and harmonic mean thicknesses of the villous membrane (maternal aspect of trophoblast to luminal aspect of vascular endothelium) were estimated. An index of the variability in thickness of this membrane, and an estimate of its oxygen diffusive conductance, was derived secondarily. Group comparisons were drawn using two-way analysis of variance to identify main effects (of PE or IUGR) and interaction effects (between PE and IUGR). PE did not have significant effects on placental morphology and there were no significant effects of PE or IUGR on membrane thickness or its variability. In contrast, IUGR (with or without PE) was associated with reduced surface areas and this was the principal factor leading to a smaller membrane diffusive conductance in these placentas. When account was taken of fetal mass, specific conductance showed no effects of PE or IUGR despite the mass-specific conductance in pure IUGR placentas appearing to be smaller than that in controls. The decline in total conductances is indicative of perturbations operating at the levels of villous trophoblast and fetal vasculature and these may contribute to fetal hypoxic stress.     

Placentae of light for dates infants born to underweight mothers at term: a morphometric study

Fifteen light for dates infants and their placentae were compared to 15 well-grown infants and their placentae. The former were born to thin, underweight women while the latter were born to women of normal weight. The light for dates infants were symmetrically growth retarded but not wasted at delivery and their placentae had a reduced weight, volume, chorionic surface area, percentage parenchyma and total villous surface area. The peripheral villous surface area and volume of peripheral villous trophoblast, fetal capillaries and connective tissue was also reduced in the placentae of light for dates infants, suggesting retarded placental growth in the latter half pregnancy. In contrast, the stem villous surface area and volume of stem villous trophoblast, fetal capillaries and connective tissue was similar in both groups of placentae, suggesting the same rate of growth in early pregnancy. There were no differences in the volume of fibrin or infarcts. The ratio of total villous surface area to infant weight, length and head circumference was reduced in the light for dates infants. This may restrict the materno-fetal oxygen exchange, and thereby increase the risk of fetal hypoxia during labour. It is concluded that the placentae of light for dates infants born at term to underweight women are both absolutely and relatively small with a reduced villous surface area.     

Effects of maternal iron restriction on placental vascularization in the rat.

To investigate the effects of maternal iron deficiency and anaemia on the placenta the composition and vascularization of the placental labyrinth was investigated in iron-restricted rats. Rats in the experimental groups were placed on iron-restricted diets either 1 or 2 weeks before mating and continued on these diets throughout gestation. Placentae were studied at day 21 of gestation. Tissue sections were stained with lectin to allow identification of fetal capillaries and analyzed using stereological techniques. Capillary surface area density and total capillary surface area were decreased in both iron-restricted groups compared with the control group. Capillary length density was decreased in both iron-restricted groups compared with the control group. Total capillary length was significantly reduced in the 1-week, but not in the 2-week, iron-restricted group compared with the control group. Endothelial cell volume was increased in both iron-restricted groups compared to the controls. There were no significant differences in the volume of fetal capillaries, the volume of the maternal blood spaces or the surface area of the maternal-fetal interface between the control and iron-restricted groups. Labyrinthine volume, labyrinthine tissue volume and the surface area of the maternal fetal interface were increased in the 2-week group when compared with the 1-week group. These changes in placental vascularization may contribute to the fetal growth retardation observed in iron-restricted litters.     

Expression of vascular endothelial growth factor in third-trimester placentas is not increased in growth-restricted fetuses

OBJECTIVE: Vascular endothelial growth factor (VEGF) is considered the growth factor that stimulates vasculogenesis and angiogenesis. Recent studies have demonstrated its role in regulating placental growth and invasion. Its expression can be upregulated by hypoxia. Intrauterine growth restriction (IUGR) is thought to be associated with inadequate placental perfusion, which might result from a failure in the development of the villous vascular network. Our present study was undertaken to examine the relationship between VEGF expression and IUGR in pregnancies with preserved umbilical artery end-diastolic flow. METHODS: VEGF Expression was determined by immunohistochemical analysis of placentas from 17 pregnancies with normal infant birth weight and 17 pregnancies complicated by IUGR. RESULTS: We found no significant differences in the expression of VEGF in villous syncytiotrophoblasts and intermediate trophoblasts in maternal decidua between IUGR and normal pregnancies. However, in both groups there was a strong correlation in the expression of VEGF with villous syncytiotrophoblasts and intermediate trophoblasts. In normal and IUGR pregnancies the infants' Apgar scores at birth were significantly correlated with VEGF staining in both syncytiotrophoblasts and intermediate trophoblasts (P < .05). A strong correlation also was found between cord hematocrit and VEGF staining in villous syncytiotrophoblasts (P < .05), but VEGF staining in intermediate trophoblasts was not correlated with cord hemoglobin or hematocrit. CONCLUSIONS: Our results suggest that VEGF acts in an autocrine and paracrine fashion in both normal and IUGR placentas, and its expression can have an effect on the well being of the infant at birth.