Intrauterine growth retardation: morphometry of the microvillous membrane of the human placenta

The syncytiotrophoblast microvillous membrane of the human placenta has been investigated with quantitative analyses in cases of severe fetal growth retardation associated with a marked reduction in the surface area of exchange at the peripheral villous level. This study has shown that, in placentae of intrauterine growth-retarded infants of unknown origin, there were morphological changes in the microvillous membrane characterized by an increase in the microvillous surface density and surface enlargement factor, associated with a reduction of the intermicrovillous space. It is not possible to state whether these morphological changes represent a delayed maturation of the placental tissue, or compensatory mechanisms to improve the functional efficiency of the placenta. In pre-eclampsia, these placental changes were much less pronounced, possibly due to severe uteroplacental ischaemia in this complication of pregnancy. Despite these morphological changes, both groups of placentae showed significant reductions in absolute values for the microvillous and total trophoblastic surface areas, which can have major implications on the functional efficiency of the placenta.     

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.     

Study on Na+ and L-alanine cotransport of the human placenta using microvillous membrane vesicles

Using microvillous membrane vesicles prepared from human normal term placenta, placental cotransport system of Na+ and L-alanine was studied using rapid filtration technique. The uptake of L-alanine into microvillous membrane vesicles was Na+ ion electrochemical gradient (extravesicular greater than intravesicular) dependent and showed typical overshoot phenomenon. Both Na+ dependent L-alanine uptake and Na+ ion uptake into microvillous membrane were membrane potential dependent and were markedly increased when the intravesicular space was rendered electrically more negative by membrane diffusion potentials, induced by the use of highly permeant anions. L-alanine gradient (extravesicular greater than intravesicular) induced a temporary accumulation of Na+ ions. These results indicated that L-alanine and Na+ ions were cotransported across microvillous membrane and this cotransport was dependent on the electrical potential difference in the membrane.     

Intracellular and extracellular pH dynamics in the human placenta from diabetes mellitus

The placenta is a vital organ whose function in diseases of pregnancy is altered, resulting in an abnormal supply of nutrients to the foetus. The lack of placental vasculature homeostasis regulation causes endothelial dysfunction and altered vascular reactivity. The proper distribution of acid- (protons (H⁺)) and base-equivalents through the placenta is essential to achieve physiological homeostasis. Several membrane transport mechanisms that control H⁺ distribution between the extracellular and intracellular spaces are expressed in the human placenta vascular endothelium and syncytiotrophoblast, including sodium (Na⁺)/H⁺ exchangers (NHEs). One member of the NHEs family is NHE isoform 1 (NHE1), whose activity results in an alkaline intracellular pH (high intracellular pH (pHi)) and an acidic extracellular pH (pHo). Increased NHE1 expression, maximal transport activity, and turnover are reported in human syncytiotrophoblasts and lymphocytes from patients with diabetes mellitus type I (DMT1), and a positive correlation between NHEs activity and plasma factors, such as that between thrombin and platelet factor 3, has been reported in diabetes mellitus type II (DMT2). However, gestational diabetes mellitus (GDM) could result in a higher sensitivity of the human placenta to acidic pHo. We summarized the findings on pHi and pHo modulation in the human placenta with an emphasis on pregnancies in which the mother diagnosed with diabetes mellitus. A potential role of NHEs, particularly NHE1, is proposed regarding placental dysfunction in DMT1, DMT2, and GDM.     

Histomorphometry of the human placenta in maternal preeclampsia

The placentas of five mothers with severe preeclampsia who gave birth to moderately growth-retarded term infants were compared to a group of placentas collected from mothers who had uncomplicated pregnancies and normal term infants who were appropriate for gestational age. This study demonstrated that, on a quantitative histologic basis, the placentas of the preeclamptic mothers were morphologically very similar to the control placentas in terms of weight, parenchymal and cellular content, and surface areas of exchange between mother and fetus. The findings of this study support the hypothesis that, in preeclampsia not associated with severe intrauterine growth retardation, the perinatal morbidity associated with this condition is probably related more to some alterations in uteroplacental and, possibly, umbilical blood flows than to significant changes in placental structure and function. This may be due to compensatory repair mechanisms and extensive functional reserve capacities in these placentas.     

L-serine uptake by human placental microvillous membrane vesicles

The human fetus requires more glycine than any other amino acid but placental glycine transfer to the fetus is insufficient to meet fetal demand. L-Serine could represent a major metabolic source of glycine for the human fetus but little is known about the kinetics and physiology of L-serine uptake by the human placenta. We have characterised the amino acid transport systems involved in the uptake of L-serine by the microvillous membrane of the human placental syncytiotrophoblast and compared the uptake rates to those of glycine. L-Serine uptake into microvillous membrane (MVM) vesicles was primarily mediated by system A (MeAIB inhibitable) and system L (BCH inhibitable). Further characterisation using specific substrates of LAT1 and LAT2 found the pattern of L-serine uptake was consistent with that expected for uptake mediated by LAT2. Uptakes were performed with tracer levels of (14)C-L-serine, physiological levels of L-serine, or with physiological levels of amino acids. As amino acid concentrations rose, the proportion of uptake by System L decreased while uptake by uncharacterised Na(+)-independent systems increased. Uptake of Lserine into MVM vesicles had a V(max) of 2.1+/-0.4 nmol/mg protein/min, which was significantly higher than for glycine (V(max) 1.0+/-0.2 nmol/mg protein/min). This indicates that MVM vesicles have a higher uptake capacity for L-serine than glycine, despite a greater demand for glycine over serine for fetal protein synthesis. Further studies are now required to define the fate of L-serine taken up by the placenta and its importance for the fetus.     

Immunoferritin localisation of antigens of the microvillous membrane of human trophoblast

Antiserum raised to purified plasma membranes of the human trophoblast (TrPM) was used in an indirect immunoferritin method to investigate the expression of specific membrane antigens in explants of human trophoblast and in cultured cells. Ferritin deposits occurred in discrete regions on the microvillous membrane of the syncytiotrophoblast, and these deposits also occurred in coated areas of the membrane. Discrete staining was also seen in cultured trophoblast cells and HeLa cells. Human amnion cells had a strong positive reaction for the TrPM antigens, but foetal skin cells and HEp-2 (larynx carcinoma) cells were negative. TrPM antigens appear to be highly specific for trophoblast and amnion, only being found otherwise as a result of placental genomic re-expression in neoplasia.     

Morphometric evaluation of the microvillous surface enlargement factor in the human placenta from mid-gestation to term

The factor by which the villous surface area is enlarged owing to the presence of microvilli has been evaluated with quantitative analyses in human placental tissues from mid-gestation to term. It has shown that, between 25 and 36 weeks of gestation, the peripheral villous surface area is enlarged by a constant factor of approximately 9.47 +/- 0.28 (mean +/- s.d.). Then, from 36 weeks to term, it has shown a significant decrease in the microvillous surface enlargement factor (9.44 to 7.67; P less than 0.01). Consequently, the actual surface area of exchange between mother and fetus was shown to be significantly decreased during that same period (93.91 to 67.02 m2; P less than 0.01). On a functional basis, these findings support the theory that, during that last four weeks of pregnancy, the increasing physiological needs of the fetus are probably met by profound functional changes in the permeability and transfer functions of the cells that constitute the placental barrier.     

Morphometric mitochondrial studies in the placenta of early pregnancies following a normal course of pregnancy and in maternal diabetes mellitus

89 electron micrographs from a diabetic placenta of the 8th week of pregnancy and from two normal placentas of the same period of gestation are investigated morphometrically. In the trophoblast mitochondria of the diabetic placenta the surface/volume ratio between the surface of the cristae and mitochondrial volume shows a statistically significant reduction as compared to the values in the normal placenta of the same period of gestation. The morphological changes of the placenta are being related to disorders of the regulation of the metabolic processes in diabetes mellitus in early pregnancy.     

A study on the mechanism of bile acid transport in the human placenta (the passive transport system of taurocholate across microvillous membrane)

The uptake of taurocholate into microvillous membrane vesicles prepared from human normal full term placenta was studied using a rapid filtration technique. The taurocholate uptake into microvillous membrane vesicles was sensitive to extravesicular osmolarity, and preincubation with the taurocholate increased the uptake of taurocholate into the vesicles. These findings indicate that the uptake of taurocholate by microvillous membrane vesicles represents transport into vesicles. The uptake of taurocholate into vesicles was not dependent on sodium electrochemical gradient (extravesicular greater than intravesicular). But, this uptake was markedly increased when the intravesicular space was rendered electrically more positive by the use of lowly permeant anions or K+ diffusion potentials via valinomycin. These findings indicated that taurocholate was transported into microvillous membrane vesicles as anion. Cholic acid inhibited the uptake of taurocholate into vesicles, but taurine didn't inhibit this uptake. The initial rate of taurocholate transport exhibited saturation kinetics with respect to the taurocholate concentration; an apparent Km of 67 microM and Vmax of 0.30n mol/mg protein/20 sec were calculated. These results indicated that placental taurocholate transport was not active but passive (facilitated diffusion), and taurocholate was transported from fetus to mother via placenta because the blood concentration was higher in fetus than mother.     

Effects of gestational diabetes mellitus on proteins implicated in insulin signaling in human placenta.

OBJECTIVE: Placenta plays a central role in fetal nutrition. During gestational diabetes mellitus (GDM), it suffers structural and functional alterations which affect the health of both mother and fetus. In the present study we aimed to clarify if GDM modifies the amounts of leptin receptor (Ob-R) and of the main proteins implicated in insulin signal transmission (insulin receptor, insulin receptor substrate-1 and phosphatidylinositol-3-kinase subunit p85alpha) in human placenta; we also attempted to confirm the presence of estrogen receptor-alpha to determine the effect of GDM on its amount. METHODS: Placentas were recovered from 30 women with uncomplicated pregnancies and 20 women who developed GDM. Western blotting and immunocytochemistry experiments were performed to investigate the above-mentioned proteins. RESULTS: We observed that all proteins studied were increased in GDM. However, it is unknown if this is a consequence of GDM or the result of medical treatments used to mitigate the injurious effects of GDM. CONCLUSIONS: Probably, the changes we found are indicative of the protective role of the placenta prior to the injurious effects of GDM and/or an important indicator of placental aging. Some aspects related to the link between non-genomic estrogen action, the mitogenic action of insulin and the role of Ob-R in placenta from normal and GDM women need to be investigated in greater depth.