Placental pathology in women with type 1 diabetes and in a control group with normal and large-for-gestational-age infants

Unexplained intra-uterine fetal death is still a problem in diabetic pregnancies, especially in those with an LGA-infant. We hypothesized that in these pregnancies impaired placental function, in terms of abnormal placental weight and/or abnormal placental histology, may account for this phenomenon. To test this hypothesis, we assessed the relative placental weight and scored several histological abnormalities in 34 AGA- and 24 LGA-placentae of type 1 diabetic women and in 22 AGA- and 16 LGA-placentae of control women. Relative placental weight was comparable in the LGA-diabetic cases and in the control groups, but was significantly higher in the AGA-diabetic subgroup. Histological abnormalities such as the presence of nucleated fetal red blood cells, fibrinoid necrosis, villous immaturity and chorangiosis were observed more often in the diabetic placentae compared with the control placentae. These differences in histology were particularly observed when we compared both AGA-groups. LGA-control placentae showed a high incidence of histological abnormalities, almost comparable to the diabetic placentae. Only fibrinoid necrosis was significantly more common in the LGA-diabetic placentae. Three of the four cases of perinatal death/asphyxia in the diabetic group concerned an LGA-infant with a relative low placental weight. In conclusion, placentae of women with type 1 diabetes showed several abnormalities that can be associated with impaired functioning. The difference between AGA- and LGA-diabetic placentae was related to relative placental weight and our data suggest that an increase in relative weight may protect the fetus from asphyxia. Placentae from LGA-non-diabetic women showed several similarities to those of women with diabetes.     

Relation between placental morphometry and fetal growth]

Forty-eight placentae of full term infants, 21 placentae from appropriate for gestational age infants (AGA) and 27 placentae from small for gestational age infants (SGA) were measured by morphometric technic using the automatic image analyzer, in order to find out the extent of fetomaternal exchange which determines the transfer of oxygen and nutrition from mother to fetus and fetal growth. The results of measurement correlated well both with infant birth weight and placental weight. They demonstrated striking quantitative differences when the placentae of SGA were compared with those of AGA. The placenta weights in the group of SGA were notably less than those in the group of AGA. It seems that low birth weight relates to low functional tissue mass of placenta. This reduction of functional tissue is accompanied by diminution of the area for exchange between mother and fetus, both at the villous surface area and at fetal capillary surface area. Thus, the ability of transferring oxygen and nutrition from mother to fetus is curtailed. The results show that the rate of fetal growth is limited by placental function as well as its weight.     

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。     

Monoamine oxidase expression and activity in human placentae from pre-eclamptic and normotensive pregnancies

A feature of pre-eclampsia is that circulating levels of maternal serotonin (5-hydroxytryptamine) are elevated and placental monoamine oxidase-A (MAO-A) activity, the major factor in the regulation of serotonin levels in pregnancy, is reduced. It is not known whether this is due to a reduced MAO-A protein content or a reduced catalytic turnover of the serotonin by MAO-A; this question has been addressed in the present work. Term placentae from normotensive and pre-eclamptic women were analysed for MAO-A specific mRNA expression (by semi-quantitative RT-PCR), MAO-A protein (by immunohistochemistry and quantitative ELISA, using a MAO-A specific monoclonal antibody), together with MAO activity (using [(3)H] labelled 5-hydroxytryptamine as substrate). Immunohistochemical analysis of placentae from both normotensive and pre-eclamptic women demonstrated that MAO-A protein is located in the cytoplasm of the placental syncytiotrophoblast layer, consistent with a mitochondrial location; no MAO-A protein was found in the nucleus. No MAO-B protein was detected in this placental layer, despite the presence of MAO-B mRNA. The results indicate that both total protein/g fresh weight and MAO-A protein/g fresh weight were approximately 40 per cent lower in pre-eclamptic than in normotensive placentae, but that there was no statistical difference in the expression of MAO-A mRNA in relation to GAPDH or actin mRNA or in MAO-A protein/mg total protein. However, MAO-A activity/g fresh weight was significantly reduced in pre-eclamptic placentae, in agreement with previous findings. This was found to be due to a 60 per cent reduction (P< 0.05) in the catalytic turnover (activity/molecule) of the enzyme. This study has therefore clearly shown that the expression of placental MAO-A specific mRNA and MAO-A protein are not specifically affected in pre-eclampsia, but that the catalytic efficiency of the expressed MAO-A enzyme in pre-eclamptic placentae is greatly reduced.     

Serial human placental lactogen estimations in serum and placental weight-for-dates.

The relation between serial HPL assays in serum and placental weight-for-dates was studied in 70 randomly chosen pregnant women. Out of five different aspects of the HPL curve only a fall below the 2-3d centile without subsequent recovery was related to low placental weight. When a small-for-dates (SFD) placenta was associated with normal HPL levels, maternal body weight tended to be lower than if both placental weight and HPL levels were abnormal. This suggests that physiologically small placentae are discernible from pathologically small placentae by a normal HPL curve.     

The placenta in leprosy

Eighty-one placentae from women with leprosy and 17 placentae from healthy controls were subjected to a detailed macroscopic, light microscopic, ultrastructural, immunopathological, microbiological and biochemical study. The placental morphology and immunohistology were normal, and there was no morphological evidence of infection of the placenta due to M. leprae. No acid-fast bacilli or acid-fast bacillary granules were seen on light microscopy of any of the placentae from leprous women, although homogenates from two out of seven placentae from women with very active lepromatous leprosy contained acid-fast bacilli in very small numbers. The small placental size of women with leprosy, most marked in those with lepromatous leprosy, appears to be due to a decrease in placental cell size, rather than to a reduced number of cells in the placenta. It is postulated that the small placenta and reduced fetal birth weight observed in lepromatous leprosy are a consequence of depressed maternal immune reactivity.     

Raised maternal serum alpha-fetoprotein in the absence of fetal abnormality--placental findings. A quantitative morphometric study

Ten placentae from pregnancies proceeding to term from mothers who on routine screening at 16-18 weeks gestation were found to have raised serum AFP but no increase in amniotic fluid AFP and no fetal abnormality, were studied using morphometric techniques. The results were compared with 20 placentae from normal term pregnancies where the maternal serum AFP level was not elevated. The mean total placental volume, volume of parenchyma and villous surface area were increased in the placentae associated with a raised maternal serum AFP. More of these placentae were infarcted and the fetal-placental weight ratio was significantly lower. The hypothesis that elevation of maternal serum AFP level is related to the increase in placental size is addressed.     

Weights of placentae from small-for-gestational age infants revisited

The objective of the study was to investigate the association between placental weight and birthweight in appropriate (AGA) and small for gestational age (SGA) infants. Placental weight, birthweight and their ratio in chromosomally normal singleton pregnancies with SGA (n=1569) and AGA (n=15 047) infants were compared, and their determinants were studied by logistic regression. SGA infants had 24 per cent smaller placentae than AGA infants when gestational age was used as a covariate. Placental actual weight was also lower in SGA infants than in AGA infants of the same birthweight (P< 0.001). SGA infants had smaller placentae than the controls, suggesting that fetal growth depends on the actual weight of the placenta. Future studies should evaluate whether growth restriction could be reversed by therapeutic approaches increasing placental weight.     

Correlation between human chorionic somatomammotropin and placental weight.

Human chorionic somatomammotropin concentration in serum (S-HCS) during the latter half of pregnancy was measured by radioimmunoassay and correlated to the placental weight, in two groups of normal, healthy, pregnant women. In one group, 228 samples from 47 women were examined, which gives a longitudinal series. In the other group, single samples from each of 346 pregnant women were examined, which gives a cross-sectional series. Both groups were randomized on the basis of a prospective selection. The mean values of S-HCS in each week of gestation were almost identical in the two groups, showing a steady increase until 37-38 weeks and a subsequent decrease. In the longitudinal series there was a positive correlation between the S-HCS and placental weight after 37 weeks' gestation, but not before that time. Before 37 weeks gestation the ratio S-HCS/placental weight was significantly higher with small placentae than with large placentae. This difference between small and large placentae disappeared after 37 weeks. These results point to the existence of some regulatory mechanism tending to keep the S-HCS concentration within certain limits, independent of placental weight. This mechanism appears to be lost after 37 weeks of gestation when the S-HCS concentration starts to correlate with placental weight.     

Stereological study of the placentae in intrauterine growth retardation with different ponderal index]

10 placentae each from the cases of IUGR with normal ponderal index (NPI) and low ponderal index (LPI) and 10 from normal pregnancy as control were analysed quantitatively with stereological principles. This study showed the placental weight, volume, surface area of villi and villous fetal capillary in IUGR were significantly reduced than that in control group. The percentage ratio of the fetal capillary volume was increased significantly in IUGR group but the ratio of vasculo-syncytial membrane/villous fetal capillary decreased. It suggested that compensation to anoxemia in placenta of IUGR was incomplete. The data also found that all the parameters in NPI group were decreased significantly than that in LPI group, which implied NPI group had a more severe growth deficiency of the placental functional structure. When placental growth deficiency occurs in the first or second trimester, both the fetal length and weight will be severely affected.     

Sex-specific differences in placental global gene expression in pregnancies complicated by asthma

Background

Chronic maternal asthma is associated with reduced growth of the female fetus and normal growth of the male fetus. The mechanisms that control the differential effects of maternal asthma on the fetus have not been fully elucidated but alterations in placental function may play a role. In the current study we have used microarray platform to examine fetal sex-specific global changes in placental gene expression in pregnancies complicated by asthma as compared to non-asthmatic subjects.

Methods

Placental RNA was extracted from 11 control subjects and 38 asthmatic subjects. Labeled cDNA was hybridized to an oligonucleotide chip with 1700 double spotted well-characterized human genes. Global gene expression data analysis and visualization were performed using the Binary Tree-Structured Vector Quantization (BTSVQ) software. Functional relationships of differentially expressed genes were assessed using protein-protein interaction database I2D, network analysis and visualization software NAViGaTOR and Ingenuity Pathway Analysis software.

Results

Overall, 65 genes were found to be altered in placentae of pregnancies complicated by asthma. Of these, only 6 genes were altered in male placentae. There were 59 gene changes in female placentae of asthmatic mothers relative to control placentae. Some of the sex-specific genes were associated with growth, inflammation and immune pathways.

Conclusion

There are sex-specific alterations in placental gene expression in the presence of maternal asthma. Given that many of the identified genes in the female placentae were associated with or involved in cellular growth and tissue development, these may contribute to the sexually dimorphic difference in fetal growth in response to maternal asthma.     

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.     

Placental weight in diabetic pregnancies

The placenta from 30 women with diabetes mellitus were examined and weighed at delivery. Nineteen of these were from women with overt and eleven from women with gestational diabetes. Eleven placentae from normal pregnancies served as controls. There was no difference between the mean +/- s.d. placental weight for the diabetic group and the control group (609 +/- 148 versus 591 +/- 93 g, NS). The mean placental weight ratios for the diabetic group and the control group were also similar (0.98 +/- 0.23 versus 0.89 +/- 0.15, NS). Moreover, there was no difference between the weights and weight ratios of placentae from women with overt (622 +/- 173 g, 1.02 +/- 0.27) and those with gestational diabetes (586 +/- 90 g, versus 0.90 +/- 0.13). Placental weights correlated with birthweights (r = 0.70, P less than 0.01) and with skinfold thickness measurements fo the infants (r = 0.40, P less than 0.05), but neither with gestational ages (r = 0.15, NS) nor with maternal glycosylated haemoglobin levels in the third trimester (r = 0.24, NS). Among the women with overt diabetes, placental weights were greater in those in White's class B and C than those in class D and R (689 +/- 143 versus 530 +/- 177 g; P less than 0.05). In general, placentae from well controlled diabetic patients were not heavier than those from normal pregnant women, although there was an increase in placental weight in White's class B and C, as compared with those in class D and R.     

Placental growth from the first to the second trimester of pregnancy in SGA-foetuses and pre-eclamptic pregnancies compared to normal foetuses

The aim of this study was to determine placental growth between 12-22 weeks in normal pregnancies compared to pregnancies complicated by foetal SGA and maternal pre-eclampsia (PE). The placentae of 1199 women were measured 3D sonographically at 12, 16 and 22 weeks of gestation. Placental volume growth was then calculated. Neonatal birthweight, birth centile and the occurrence of pre-eclampsia were recorded in every woman and correlated with placental growth (four groups: normals, SGA, PE, SGA+PE). SGA-placentae are already smaller at 12 weeks but then develop in a similar way to normal placentae. PE placentae are slightly, but significantly, larger at 12 weeks, grow rapidly until 16 weeks and then stop growing normally between 16 and 22 weeks. If SGA goes together with PE, both placental volume (PV) at 12 weeks as well as growth is reduced significantly. Nevertheless, placental growth between week 12 and 22 is too heterogeneous to justify using this method as a clinical tool, but it can provide new information on placental physiology underlying unfavourable obstetric outcomes.     

Placenta of idiopathic fetal growth restriction: cytochemically detectable enzyme activities do not change at a subcellular level

The present study was designed to localize some important enzymes, such as adenosine diphospate-degrading enzyme (ADP-degrading enzyme) (plasma membrane enzyme), cytochrome c oxidase (mitochondrial enzyme) and glucose-6-phosphatase (endoplasmic reticulum enzyme), in placentae from patients with idiopathic fetal growth restriction (FGR) associated with absent end-diastolic flow velocity in the fetal umbilical artery. We compared these enzyme activities and their localization patterns to those in placentae both from pre-eclampsia with FGR and normal pregnancy with appropriate for their gestational age infants. In idiopathic FGR placentae, the intensity and localization patterns of these three enzymes did not differ from those seen in the placentae from normal pregnancy. Decreased ADP-degrading enzyme activity and cytochrome c oxidase negative mitochondria, which were characteristic features of pre-eclamptic trophoblasts, were absent from trophoblasts of the idiopathic FGR placentae. These observations indicated that enzyme-cytochemically detectable trophoblastic cell dysfunction may be absent in idiopathic FGR, or if present, there is less functional impairment of each trophoblast in this disease than in pre-eclampsia. Though both idiopathic FGR and pre-eclampsia lead to placental insufficiency, and finally to restricted fetal growth, a different mechanism and pathophysiology may work at the cellular and subcellular levels in these two diseases.     

Histomorphometry of the human placenta in Class C diabetes mellitus

Placentae from Class C diabetic mothers were compared by histomorphometric analyses with a group of normal placentae. The placentae of the diabetics were divided in two groups based on the growth characteristics and neonatal outcome of the infants at birth. This study has demonstrated that the placentae of both groups were somewhat heavier than the controls due to a parallel increase in parenchymal and non-parenchymal tissues. The placentae were also shown to be characterized by a relative increase in the surface areas of exchange between mother and fetus, in terms of peripheral villous and capillary surface areas and intervillous space volume. Consequently, the results of this study suggest that, in Class C diabetics, placental morphology and placental function are probably not more adversely affected than in other less severe forms of the disease during pregnancy. Furthermore, the findings in this investigation support the hypothesis that the placental changes, and the perinatal morbidity associated with this condition, are probably the results of hormonal and metabolic abnormalities present in the mother and the fetus.     

Angiotensin II type 1 receptor has impact on murine placentation

Impaired placentation is a key step in the pathogenesis of important pregnancy disorders such as preeclampsia and fetal growth restriction. A role of angiotensin II in placental development can be assumed from the expression of angiotensin receptors on trophoblast from the earliest stages of pregnancy. To understand the role of angiotensin II type 1 (AT1) receptors in placental development, we investigated placentae of AT1a-deficient mice early in pregnancy (day 13 postconception). The number of alive newborns was significantly reduced in AT1a-deficient mice caused by placental malformations in 30% of all utero-placental units. Importantly, no embryonic structure was observable within the uterine segments harboring the malformed placentae. Immunohistochemistry with an antibody against murine betahCG-equivalent stained homogenously in almost all cells in the altered placentae indicating still an endocrine-active trophoblast. However, the typical structure of the murine wild-type placenta in spongiotrophoblast, giant cells, and labyrinth was abolished in malformed placental tissue deficient in the AT1a receptor. Recent epidemiological studies revealed the detrimental effect of an AT1 blockade for fetal outcome due to renal malformations and a reduced birth weight. For the latter, our findings provide an early mechanistic explanation. The lack in AT1 stimulation causes an impaired trophoblast maturation leading to impaired placental function.     

Abruptio placentae and chorioamnionitis-microbiological and histologic correlation.

BACKGROUND: To determine the association of chorioamnionitis with placental abruption. SUBJECT AND METHOD: Fifty pregnant women admitted with abruptio placentae were compared to an equally large control group in spontaneous labor with no history of antepartum hemorrhage. Swabs from the cervix and placental membranes were cultured for aerobic and anaerobic organisms. Placental membranes were studied histologically in 40 women of study group and 35 of control group for any evidence of chorioamnionitis. RESULTS: Specific organisms were isolated in 22 (44%) women in the study group and 19 (38%) women in the control group. The cervical swab microbiological flora was similar in both groups but isolation of specific organisms from placental membrane culture was higher in the study group (40%) compared to the controls (18% p<0.05). Evidence of histologic chorioamnionitis was higher in the study group 12/40 (30%), than in the control group 8/35 (22.85%), but the difference was not significant. CONCLUSION: The incidence of silent chorioamnionitis (placental membrane culture positivity) is higher in the abruptio placentae.     

Distribution of Placental Grading by Gestational Age

Objective: to describe the ultrasonography-based gestation-specific placental grading distribution in a Chinese population.Methods: ultrasonographic examination of placentae was performed in 5,476 normal pregnancies (more than 95% first births) in five obstetric ultrasound laboratories in Central-South China between January 1, 1992 and December 31, 1993. A gestation-specific placental grading distribution was presented and compared with previous studies.Results: the gestational ages of the patients included in this study ranged from 16 to 40 weeks. The gestation-specific distribution of placental grading showed patterns similar to those observed previously, with grade III placentae starting to occur at 32 weeks and increasing to 32.3 percent at 40 weeks of gestation.Conclusions: the occurrence of grade III placentae is too high in preterm and too low in term pregnancies. Ultrasonographic placental grading alone is not a reliable measure of fetal pulmonary maturity.