Search PubMed⌕ Search

Biomedical subjects

T M Mayhew

Publications and source records attributed to T M Mayhew.

At least 37 records · Page 2Linked to original sources
PubMed2001

Villous trophoblast of human placenta: a coherent view of its turnover, repair and contributions to villous development and maturation.

A coherent view of human villous trophoblast as a continuously renewing epithelium is presented. Epithelia undergoing continuous renewal (e.g. intestinal mucosa, epidermis) display clonogenic cells which pass through several transit divisions before migrating out of proliferation zones and into zones of maturation/differentiation. Quantitative relations (e.g. relative numbers of cells) between proliferation and differentiation zones help to define the steady state and this may vary in response to physiological and pathological circumstances. From the differentiation compartment, cells or cell fragments are eventually extruded by mechanisms which may involve apoptosis. All these features are seen in trophoblastic epithelium. Cytotrophoblast cells (CT, proliferation zone) divide continuously throughout gestation and post-mitotic cells are recruited into syncytiotrophoblast (ST, differentiation zone) after membrane fusion. Evidence of fusion events includes localised confluence of CT and ST cytoplasms, and intrasyncytial plasma membrane segments bearing desmosomal remnants. During differentiation, nuclei undergo changes in shape, chromatin condensation and packing density. Densely-clustered nuclei are associated with cytokeratin intermediate filaments and annulate lamellae. Both clustered and non-clustered nuclei show ultrastructural features of pre-apoptosis and apoptosis. Normally, apoptosis is triggered only when nuclei are in the syncytium. Some (pre-)apoptotic nuclear aggregates are sequestered in syncytial knots, extruded as trophoblast fragments into the intervillous space and then deported into the maternal circulation to be phagocytosed at extraplacental sites. During gestation, there is some constancy in the numerical ratios between CT and ST nuclei pointing to a normal steady state. The steady state may be perturbed when the epithelium is damaged locally. Where the epithelium is denuded, fibrin-type fibrinoid from the intervillous space plugs the discontinuity and, with CT proliferation, facilitates reepithelialisation. Features of normal villous development (e.g. sprouting, intervillous bridge formation, bridge abruption, syncytial knot formation) are explicable in the context of trophoblast turnover with early CT proliferation being mainly for growth and later proliferation for renewal and repair. Adaptive re-settings of the epithelial steady state may also occur in abnormal pregnancies.

Adult↗
PubMed2000

Effects of gestational diabetes on junctional adhesion molecules in human term placental vasculature.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether gestational diabetes mellitus, which occurs in the microvascular remodelling phase of placental development, causes alterations in surface expression of tight and adherens junctional molecules involved in endothelial barrier function and angiogenesis. METHODS: Term placenta, delivered by elective Caesarian section, from normal pregnancy (n = 5) and those complicated by gestational diabetes (n = 5) were perfusion-fixed and analysed by indirect immunofluorescence and confocal scanning microscopy. Using systematic random sampling, the surface expression of endothelial junctional proteins and the relative incidences of immunostained vessels were compared between the two study groups. Total vessel lengths were measured by stereological techniques. RESULTS: The adherens junctional molecules, vascular-endothelial cadherin and beta-catenin, and the tight junctional molecules, occludin and zonula occludens-1 were localised to paracellular clefts in both study groups. The diabetic placentae showed pronounced reductions in the intensity of immunofluorescence and in the number of immuno-positive vessels. A corresponding statistically significant increase (from 19% to 56%) in the percentage of vessels showing junctional anti-phosphotyrosine immunoreactivity was found. The differences observed represented real changes in the absolute lengths of immunostained regions along the vessels. The stereological measurements failed to detect any statistically significant change in the combined length of fetal vessels in gestational diabetic placenta. CONCLUSION/INTERPRETATION: Our results suggest that even short duration diabetic insult, alters the surface expression of placental junctional proteins. This alteration could be mediated by the tyrosine-phosphorylation pathway. The changes suggest impaired barrier function rather than accelerated vascular growth.

Antigens, CD↗
PubMed2000

Numerical aberrations of chromosomes 1 and 17 correlate with tumor site in human gastric carcinoma of the diffuse and intestinal types. Fluorescence in situ hybridization analysis on gastric biopsies.

Recent studies predict that tumor aneuploidy plays a direct role in tumor instability. The relationship between interphase cytogenetics, histology, grade, and tumor site was analyzed in 20 primary gastric carcinomas. Using fluorescence in-situ hybridization, the numerical changes of centromeric sequences of chromosomes 1, 3, 10, and 17 were directly analyzed in gastric biopsies. Polysomic copy numbers of chromosomes 1 and 17 were discovered in 63% (10 of 16) and 59% (10 of 17), respectively, of informative cancer cases. Chromosome 3 and 10 signal number changes were found in only 6% (1 of 16) and 13% (1 of 8), respectively, of informative cancer cases. There was a positive correlation between the appearance of polysomic nuclear target sites of chromosomes 1 and 17 (correlation coefficient r = 0.72; p < 0.005). Copy number changes were not significantly related to histologic subtypes of either the Laurén or WHO classifications. However, incidence of cancers having dual polysomic signal number abnormalities for both chromosomes 1 and 17 was significantly correlated to tumor location at the cardia. The data suggests that (i) human gastric cancer appears in two genomic groups that can be reliably diagnosed by fluorescence in-situ hybridization on routine biopsy sections, (ii) numerical aberrations of chromosomes 1, 3, 10, and 17 are largely independent of histologic subtypes, and (iii) polysomic copy number abnormalities of chromosomes 1 and 17 correlate to intragastric tumor site and are highest in cardia cancers, suggesting high tumor instability at this particular location.

Aged↗
PubMed2000

To what extent are the retinal capillaries ensheathed by Müller cells? A stereological study in the tree shrew Tupaia belangeri.

The cellular ensheathment of capillaries in the 3 outer capillary layers of the central retina of the adult tree shrew Tupaia belangeri was studied quantitatively by transmission electron microscopy. Using a stereological approach, the relative surface of capillary basal lamina ensheathed by Müller cells and by nonmacroglial cells (collectively termed non-Müller cells) was estimated in 5 animals. The participation of Müller cells was distinctly different in the 3 capillary layers studied. In the outermost capillary layer 1, the mean (standard deviation) percentage surface coverage by non-Müller cell processes was 46.8 (15.3)%. Much less of the capillary basal lamina was ensheathed by non-Müller cells in capillary layers 2 and 3 (3.0 (2.1)% and 0.3 (0.3)% respectively). The observed total variation of the stereological estimates for the surface fraction of Müller cells (expressed as the between-subject coefficient of variation) was significantly higher in capillary layer 1 (28.8%) compared with capillary layers 2 (2.2%) and 3 (0.3%). In capillary layer 1, the high observed total variation was due to a high biological variation among animals for the fractions of both Müller cell and non-Müller cell ensheathment. The rare occurrence of direct contacts between the capillary basal lamina and the perikarya of either microglial cells (capillary layer 3) or amacrine cells (capillary layer 2) corresponded well to the low stereological values obtained for the relative capillary surface ensheathed by non-Müller cells in these capillary layers. Previously, extensive and frequent contacts between the basal lamina of capillaries belonging to capillary layer 1 and horizontal cells had been observed in single sections. The present study quantitatively demonstrates a marked paucity of macroglial investment of capillaries located in capillary layer 1 of Tupaia. It can be concluded that horizontal cells ensheath most of the capillary surface not invested by Müller cells.

Animals↗
PubMed2000

Stereological comparison of 3D spatial relationships involving villi and intervillous pores in human placentas from control and diabetic pregnancies.

In human placenta, 3D spatial relationships between villi and the maternal vascular bed determine intervillous porosity and this, in turn, influences haemodynamics and transport. Recently-developed stereological methods were applied in order to examine and quantify these relationships. Placentas were collected after 37 wk from control pregnancies and those associated with maternal diabetes mellitus classified according to duration and severity (White classification scheme). Two principal questions were addressed: (1) are normal spatial arrangements maintained in well-controlled diabetes mellitus? and (2) do arrangements vary between diabetic groups? To answer these questions, tissue sections cut at random positions and orientations were generated by systematic sampling procedures. Volume densities of villi (terminal + intermediate), intervillous spaces and perivillous fibrin-type fibrinoid deposits were estimated by test point counting and converted to global volumes after multiplying by placental volumes. Design-based estimates of the sizes (volume- and surface-weighted volumes) of intervillous 'pores' were obtained by measuring the lengths of point- and intersection-sampled intercepts. From these, theoretical numbers of pores were calculated. Model-based estimates (cylinder model) of the hydraulic diameters and lengths of pores were also made. Second-order stereology was used to examine spatial relationships within and between villi and pores and to test whether pair correlation functions deviated from the value expected for 'random' arrangements. Estimated quantities did not differ significantly between diabetic groups but did display some departures from control values in non-insulin-dependent (type 2) diabetic placentas. These findings support earlier studies which indicate that essentially normal microscopical morphology is preserved in placentas from diabetic subjects with good glycaemic control. Therefore, it is likely that fetal hypoxia associated with maternal diabetes mellitus is due to metabolic disturbances rather than abnormalities in the quantities or arrangements of maternal vascular spaces.

Adult↗
PubMed2000

A stereological method for testing whether or not there is random deposition of perivillous fibrin-type fibrinoid at the villous surface: description and pilot applications to term placentae.

We present a stereological method for testing whether or not there is random deposition of fibrin-type fibrinoid (FTF) at the villous surface of human placenta. The method requires random sampling of tissue with test lattice lines superimposed on microscopic fields at random positions and orientations. Test lines are used to generate chance intersections with specified sub-domains of the villous surface. At least three sub-domains are distinguishable: non-syncytial knots (nonSK), syncytial knots (SK) and areas of trophoblast de-epithelialization (DEP). Other sub-domains may be included to suit individual circumstances and project aims. The relative numbers of intersections with sub-domains provide the basis for an 'expected' distribution. Subsequently, this is compared with an 'observed' distribution which can be calculated from empirical estimates of the numbers of intersections with sub-domains associated with perivillous FTF (e.g. nonSK+FTF, SK+FTF and DEP+FTF). Expected and observed distributions can be compared by a chi-squared analysis. If the null hypothesis (no difference) is rejected, chi-squared values for individual sub-domains can be analysed in order to localize and interpret sites of preferential deposition. Comparisons may be drawn for individual placentae as well as a group of placentae, thereby permitting assessment of inter-placental variability. Finally, between-group comparisons may be drawn in order to test whether or not FTF deposition patterns differ in control and other pregnancies. Worked examples of the statistical procedures are provided. Preliminary results of applications to placentae from normal and complicated (hypobaric hypoxia) pregnancies are presented. They show that FTF deposition is non-random and preferentially located at sites of de-epithelialization. De-epithelialization may be a consequence of syncytial degeneration but also, at least in part, of continuous trophoblast turnover in which syncytial fragments rich in (pre-) apoptotic nuclei detach from the epithelium and are deported from the maternal intervillous space. The nascent detachment site is immediately covered by FTF prior to repair by re-epithelialization.

Altitude↗
PubMed2000

Maternal cigarette smoking and oxygen diffusion across the placenta.

The aim of this study was to test whether or not adaptations in partial, total and specific oxygen diffusive conductances occur in the placentae of women who smoke cigarettes during pregnancy and help to compensate for intrauterine fetal hypoxic stress. Tissue sections were randomly sampled from human term placentae divided into two groups (non-smokers and smokers) according to maternal smoking status. In smokers, status was expressed as either declared smoking rate or level of plasma cotinine (the major metabolite of nicotine). Sections were analysed stereologically to estimate key structural quantities (vascular volumes, exchange surface areas, tissue diffusion distances). These were combined with previously-published physicochemical quantities (oxygen-haemoglobin reaction rates and tissue oxygen diffusion coefficients) in order to estimate the partial conductances of six tissue compartments of the oxygen pathway: maternal erythrocytes and plasma, villous trophoblast, villous stroma (including fetal capillary wall), fetal plasma and erythrocytes. From partial conductances and birthweights, total and specific conductances were calculated for each placenta. Results were assessed statistically by analyses of variance and t -tests. Despite apparent improvements in the partial conductances of the maternal erythrocytes and plasma, total and specific conductances did not alter significantly in smoking groups. However, the relative biases affecting these estimates may be different in smokers and non-smokers. We conclude that total conductance does not increase in placentae associated with maternal smoking. However, given that the fetus suffers chronic hypoxic stress as a consequence of smoking (evidenced here by elevated haematocrits), even a constant diffusive conductance implies a reduced transplacental partial pressure gradient. This could be a contributory factor to the reduced birthweight.

Adult↗
PubMed1999

Ventricular myocardium in control and growth-retarded human fetuses: growth in different tissue compartments and variation with fetal weight, gestational age, and ventricle size.

The aim of this study was to assess the growth of different tissue compartments in ventricular myocardium of control and intrauterine growth-retarded (IUGR) human subjects. Stereological counting and sizing methods were applied to cross-sectional samples of hearts collected post mortem at 16 to 35 (control) and 32 to 42 (IUGR) gestational weeks. Total tissue volumes and total numbers of myocyte, connective tissue, and endothelial cell nuclei were estimated. In control hearts, the volume of each tissue compartment increased linearly over the period of gestation, and this was due to proliferation, because in each case the tissue volume per nucleus remained constant. In IUGR subjects, fetal weight, ventricle volume, myocyte volume, connective tissue volume, and endothelial nuclear number were less than expected for gestational age up to at least 35 weeks. Between this age and 8 postnatal weeks, these variables are predicted to achieve equivalence with values found in control fetuses. Similar deficits were found when variables were related to fetal weight, and it is predicted that equivalence with control values would be reached at weights of between 2.3 and 3.6 kg. No such differences between groups were detected when variables were related to ventricle size. These findings indicate that growth deficits in cardiomyocytes are accompanied, and may be influenced, by developmental delays that involve the intramyocardial interstitium (capillary bed, endothelium, and surrounding connective tissues). The delays and deficits exhibit "catch-up" to control values between 35 weeks and term.

Embryonic and Fetal Development↗
PubMed1999

Effects of neonatal capsaicin administration on the numbers and volumes of neurons in left and right T10 dorsal root ganglia in the rat.

The long-term effects of neonatal capsaicin were studied in left and right dorsal root ganglia (T10) from control and capsaicin-treated groups of Wistar rats. At 12 hours post partum, 5 females per group were injected subcutaneously with capsaicin or vehicle solution and killed at 6 months of age. Tissues were perfusion-fixed, embedded in resin and serially sectioned. A Nissl stain was used to distinguish between A and B neurons and systematic random sampling schemes were employed to obtain stereological estimates of numbers of neurons and mean volumes of their perikarya. Numbers were calculated from ganglion volumes (estimated via the Cavalieri principle) and neuron packing densities (estimated using physical disectors). Mean perikaryal volumes were calculated from packing densities and volume densities (estimated by point counting). Data were analysed to isolate main and interaction effects of neuron subtype, laterality and treatment. There was no evidence of lateral asymmetry or interaction effects. Control ganglia contained 3320 (coefficient of variation, CV, 8%) neurons. Most (73%) were B cells with a mean volume of 13,100 microm(3) (CV 17%) of which the nucleus accounted for 1,800 microm(3) (CV 18%). About 22% were A cells with a mean volume of 79,800 microm(3) (CV 24%) and a nucleus of 6,100 microm(3) (CV 26%). After capsaicin, over half the original population of cells was destroyed and B cell loss was significantly greater than that of A cells (about 80% of all cells lost were B cells). The mean size of A cells was greater after capsaicin due to selective loss of smaller cells and a greater volume of cytoplasm. B cell perikaryal volume was not affected but nuclear volume declined. The findings show that capsaicin destruction of peripheral sensory neurons is bilaterally symmetrical. In general, smaller neurons are selectively destroyed but this operates differently in A and B cells. It is size-dependent in A cells but size-independent (possibly random) in B cells.

Animals↗
PubMed1999

Second-order stereology and ultrastructural examination of the spatial arrangements of tissue compartments within glomeruli of normal and diabetic kidneys.

The present study explores 3D spatial arrangements of compartments within the rat renal glomerulus and tests for differences after chemically-induced diabetes. In particular, the arrangements of capillaries, podocytes, mesangium and urinary space are quantified and compared between (a) kidneys within groups and (b) kidneys from streptozotocin-diabetic rats and age-matched controls. The stereological tool employed is the pair correlation function which is estimated by counting linear dipole probes of different sizes superimposed on ultrathin sections so as to be random in position and orientation. Unbiased estimates of the volume density of each glomerular component were estimated by point counting. Thereafter, estimates of the covariance and pair correlation function were determined from corresponding dipole counts. Plots of covariance and pair correlation functions against dipole length were almost identical in control and diabetic groups, indicating that diabetes did not disturb the normal spatial arrangements within glomeruli. However, differences were detected between compartments within groups. Whilst volume elements within all compartments were clustered at distances below about 8 microm (the approximate size of the basic cellular or other structural unit), the cluster size varied between compartments. The pattern was one of progressively smaller clusters in the sequence capillaries, podocytes, urinary space, mesangium. Beyond a distance of 8 microm, all glomerular components (in both control and diabetic groups) were arranged as expected for a 'random' (meaning neither clustered nor repulsed) volume process. These studies re-emphasize the relative invariance of biological organization and the value and limitations of covariance analysis for quantifying different levels of organization in different tissues and experimental groups.

Animals↗
PubMed1999

Quantitative description of the spatial arrangement of organelles in a polarised secretory epithelial cell: the salivary gland acinar cell.

Previous quantitative descriptions of cellular ultrastructure have focused on spatial content (volume, surface area and number of organelles and membrane domains). It is possible to complement such descriptions by also quantifying spatial arrangements. Hitherto, applications of stereological methods for achieving this (notably, estimation of covariance and pair correlation functions) have been confined to organ and tissue levels. This study explores 3-dimensional subcellular arrangements of key organelles within acinar cells of rabbit parotid salivary glands, highly polarised epithelial cells specialised for exocrine secretion of alpha-amylase. It focuses on spatial arrangements of secretion product stores (zymogen granules), rough endoplasmic reticulum (RER) and mitochondria. Systematic random samples of electron microscopical fields of view from 3 rabbits were analysed using test grids bearing linear dipole probes of different sizes. Unbiased estimates of organelle volume densities were obtained by point counting and estimates of covariance and pair correlation functions by dipole counting. Plots of pair correlation functions against dipole length identified spatial arrangement differences between organelle types. Volumes within RER and mitochondrial compartments were positively correlated with themselves at distances below 4 microm and 2 microm respectively but were essentially randomly arranged at longer distances. In sharp contrast, zymogen granules were not randomly arranged. They were clustered at distances below 6-7 microm and more widely scattered at greater distances. These findings provide quantitative confirmation of the polarised arrangement of zymogen granules within acinar cells and further support for the relative invariance of biological organisation between subjects.

Animals↗
PubMed1999

Epithelial integrity, cell death and cell loss in mammalian small intestine.

In recent years, the different mechanisms of epithelial cell loss which occur in mammalian and avian small intestine have been re-investigated. Information is now available for a variety of mammalian types and mechanisms can be divided into two major classes: [i] those preserving epithelial integrity by maintaining intercellular tight junctions throughout early-to-late stages of cell extrusion; and [ii] those which compromise integrity by introducing breaches in epithelial continuity. Both classes are associated with the activity and/or proximity of non-epithelial cells (mainly lymphocytes and mononuclear phagocytes) located in the epithelium or underlying lamina propria. Intraepithelial lymphocytes may be involved in enterocyte targetting and killing whilst lamina propria (LP) macrophages sequester cell debris. Where epithelial integrity is maintained, two types of loss can be identified. In the first (type 1), complete cells are extruded into the lumen. In the second (type 2), only anucleate apical cell fragments pass into the lumen. There are two variants of type 2 loss distinguishable by the fate of the nucleated basal portions of cells. One variant (type 2a) creates large intercellular spaces extending from the preserved apical cap to the basal lamina and containing enterocyte debris for phagocytosis. The second (type 2b) involves the gradual shrinkage of individual cells (which become more electron-dense) and in situ degeneration of their nucleated subapical portions in increasingly narrower intercellular spaces between adjacent healthy enterocytes. The mechanism of removal of these fragments is unclear but may be via macrophages or surrounding enterocytes. Apoptosis has been implicated in both type 1 and type 2 extrusion. In contrast, type 3 loss involves morphological changes in enterocytes which are reminiscent of those seen in necrosis and is accompanied by breaks in epithelial continuity following cell swelling, a decrease in cell electron density and total or subtotal degradation of organelles and membranes. It ends in loss of either an abnormal cell apex (with subsequent exposure of the degraded cell contents and their spillage into the lumen) or a complete cell remnant (extruded into the lumen before total disintegration of plasma membranes).

Animals↗
PubMed1998

Numbers of nuclei in different tissue compartments of fetal ventricular myocardium from 16 to 35 weeks of gestation.

The aim of this study was to examine mechanisms of growth in different tissue compartments of the ventricular myocardium of prenatal human hearts. To this end, stereological methods were applied in order to estimate tissue volumes and total numbers of myocyte, connective tissue and endothelial nuclei in hearts collected after death at between 16 and 35 weeks of gestation. Volumes of tissue compartments were obtained after multiplying volume densities (estimated by test-point counting) by ventricular volumes (estimated from ventricular mass and tissue density). Absolute numbers of nuclei were calculated in similar fashion from corresponding nuclear packing densities (estimated using physical disectors). The volumes of all three tissue compartments increased linearly over the period of gestation examined, and in each case, the increase in tissue volume appeared to be due entirely to proliferation. Numbers of all three types of nuclei increased linearly whilst tissue volumes per nucleus remained constant. The net rate of production of myocyte nuclei was 35 x 10(7) per week (2.1 million nuclei per hour). The net rate of production of connective tissue nuclei was 12 x 10(7) per week (0.7 million nuclei per hour) and that for endothelial cell nuclei was 5.1 x 10(7) per week (0.3 million nuclei per hour). Predictions are made about the postnatal ages at which adult ratios of different nuclear types might be attained.

Body Weight↗
PubMed1998

Further evidence of species variation in mechanisms of epithelial cell loss in mammalian small intestine: ultrastructural studies on the reindeer (Rangifer tarandus) and seal (Phoca groenlandica).

Ultrastructural studies were conducted on mechanisms of epithelial cell loss in the small intestine of seal and reindeer. Mechanisms maintaining epithelial integrity were distinguished from those that did not and the non-epithelial cell types involved were identified. Three types of cell extrusion were noted. In two, tight junctional integrity was preserved and anucleate apical cell fragments (rather than complete cells) were lost into the lumen. In reindeer (type 1), this involved creating large intercellular spaces extending from the preserved apical cap to the lamina propria and containing enterocyte debris probably phagocytosed by subepithelial macrophages. A variant of this process (type 2) involved the gradual shrinkage of individual cells, which became more electron-dense, and the in situ degeneration of their nucleated subapical portions. Degenerated cell fragments and membrane whorls were confined to narrow intercellular spaces between approximating adjacent healthy enterocytes. The mechanism of removal of these fragments was unclear. In both cases, the proximity of intraepithelial lymphocytes suggested that they were involved in cell targetting and killing. Evidence of apoptotic nuclei was not found but nucleated cell fragments could have been washed out of the lumen during tissue preparation. Type 2 cell loss was seen in both species, as was another mechanism (type 3) reminiscent of necrosis. In contrast to other mechanisms, this was accompanied by breaks in epithelial continuity following gradual loss of cell electron density and total or subtotal degradation of organelles and membranes. In seal, this terminated in the loss of an abnormal cell apex and exposure of the contents of the cell remnant to the lumen. In reindeer, all the cell remnants may have been extruded before total membrane degeneration but, in both species, the otherwise tight epithelial barrier was clearly breached. Again, intraepithelial lymphocytes were associated with sites of necrosis. These findings provide evidence for further species differences in mechanisms of epithelial cell extrusion and suggest that necrotic cell loss may be more common than previously admitted.

Animals↗
PubMed1998

Thinning of the intervascular tissue layers of the human placenta is an adaptive response to passive diffusion in vivo and may help to predict the origins of fetal hypoxia.

OBJECTIVES: To test the hypothesis that thinning of the placental intervascular layers, and greater variability in thickness, are positive adaptations to facilitate passive diffusion and may help to resolve different categories of fetal hypoxia. STUDY DESIGN: Placentas from 12-41 weeks of normal gestation and from pregnancies associated with fetal hypoxic stress (high altitude, diabetes mellitus) were sampled systematically, fixed in formalin, wax-embedded and quantified using stereological methods. Arithmetic and harmonic mean distances across villous trophoblast, stroma and fetal plasma were estimated by measuring randomly sampled intercept lengths. In each case, an index of variability of layer thickness was calculated by dividing the arithmetic by harmonic mean distance. This index has the value I when a tissue layer is uniformly thick but increases in value as local layer thickness becomes more variable. Comparisons between groups were drawn using variance and regression analysis. RESULTS: During pregnancy, there were significant negative correlations between layer thickness (trophoblast, stroma) and gestational age and fetal weight, and significant positive correlations between thickness irregularity and age and weight. Compared with lowland controls, high-altitude placentas possessed thinner layers but only the trophoblast and stroma (and not fetal plasma) were more variably thick. In maternal diabetes, only fetal plasma distance was reduced but fetal and stromal layers appeared to be more irregular in thickness. CONCLUSIONS: Alterations in placental intervascular layer thicknesses occur in normal and abnormal pregnancies and represent real adaptations leading to improved diffusive conductances. Differences in the tissue location of the adaptive response may depend on the nature and origins of the fetal hypoxia.

Adaptation, Physiological↗