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

Abstract

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 (terminaljintermediate), 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.

A systematic review of placental pathology in maternal diabetes mellitus

“…However, there were no observed significant histological differences among placentas (4, 44, 46-48), which suggests that may not differentially impact placental pathology. Because the population sizes of these studies were small, ranging from 2 to 40 women within each diabetic subgroup, further research comparing placental abnormalities in women with pregestational and GDM across different White classifications is warranted.…”

“…Most studies using the White classification of diabetes did not observe significant histological differences in volume and surface area of terminal villi or growth and maturational status of villi among placentas across different White classifications (4, 44, 46-48). Stoz et al found that the significant increase in the cross-sectional surface area of the terminal villi and villous circumference compared to those from normoglycemic placentas was more prominent in women with White classes A, B, or C compared to White class D (45).…”

“…Six studies compared findings across different White classifications with a normoglycemic control group (4, 44-48); five studies compared findings between pregestational and GDM with a normoglycemic control group (49-52); one study compared findings between T1DM and GDM with a normoglycemic control group (53); two studies examined differences between T1DM and T2DM (13, 15); and one study examined placental histomorphometry in women with GDM using race/ethnicity as the basis for comparison (16). Common gross and histopathologic placental findings in pregestational diabetes and GDM compared to healthy controls are provided in Table 5.…”

“…Literature demonstrates that, when maternal glucose levels are well-controlled, the placentas from women affected by diabetes are normal as evaluated by routine light microscopy (4, 5). However, several studies have identified histopathologic placental abnormalities among women even with well-controlled pregestational (6-8) and gestational diabetes (9, 10).…”

Morphometric Characteristics of Placental Villi in Pregnant Women with Diabetes

“…However, in a series of observations, no signifi cant differences were found [2]. Stereological study also revealed no differences in the structure of the placenta [7] or detected only individual changes, including increased surface area and volume of capillaries [6], volume of the villi, total diffusion capacity, and the volume of trophoblast [5]. These discrepancies are apparently due to different DM types grouping and different methods of controlling hyperglycemia.…”