A stereological perspective on placental morphology in normal and complicated pregnancies

Abstract

Stereology applied to randomly-generated thin sections allows minimally-biased and economical quantitation of the 3D structure of the placenta from molecular to whole-organ levels. With these sampling and estimation tools, it is possible to derive global quantities (tissue volumes, interface surface areas, tubule lengths and particle numbers), average values (e.g. mean cell size or membrane thickness), spatial relationships (e.g. between compartments and immunoprobes) and functional potential (e.g. diffusive conductance). This review indicates ways in which stereology has been used to interpret the morphology of human and murine placentas including the processes of villous growth, trophoblast differentiation, vascular morphogenesis and diffusive transport. In human placenta, global quantities have shown that villous maturation involves differential growth of fetal capillaries and increases in endothelial cell number. Villous trophoblast is a continuously renewing epithelium and, through much of gestation, exhibits a steady state between increasing numbers of nuclei in cytotrophoblast (CT) and syncytiotrophoblast (ST). The epithelium gradually becomes thinner because its surface expands at a faster rate than its volume. These changes help to ensure that placental diffusing capacity matches the growth in fetal mass. Comparable events occur in the murine placenta. Some of these processes are perturbed in complicated pregnancies: 1) fetoplacental vascular growth is compromised in pregnancies accompanied by maternal asthma, 2) changes in trophoblast turnover occur in pre-eclampsia and intrauterine growth restriction, and 3) uteroplacental vascular development is impoverished, but diffusive transport increases, in pregnant mice exposed to particulate urban air pollution. Finally, quantitative immunoelectron microscopy now permits more rigorous analysis of the spatial distributions of interesting molecules between subcellular compartments or shifts in distributions following experimental manipulation.

Fig. 1

Villous membrane morphology in PE and IUGR. In each schematic, height represents the arithmetic thickness of the membrane (from luminal aspect of vascular endothelium to maternal aspect of villous trophoblast). Width is proportional to total villous surface area. CT cells lie on basal lamina and some post-mitotic cells are recruited (small arrows) into ST where terminal differentiation occurs. Turnover involves loss (large arrows) of membrane-bound ST fragments (SFs) and microparticles (MPs). Membrane thickness depends on the steady state between recruitment and loss and on the proximity of fetal capillaries to overlying trophoblast. In uncomplicated term pregnancies, ST differentiation leads to apoptosis, SFs contain multiple apoptotic nuclei and there is minimal loss of MPs. In PE, proliferation and loss increase and are associated with aponecrosis. Surface areas and thicknesses are maintained by the steady state. In IUGR and PE + IUGR, surface areas decline and overall thickness is preserved. However, in PE + IUGR, MP loss is greater than in PE or IUGR alone and rates of loss in IUGR are comparable to those in controls. See also Huppertz & Herrler (2005) and Goswami et al. (2006).