Fetoplacental Angiogenesis During Gestation is Biphasic, Longitudinal and Occurs by Proliferation and Remodelling of Vascular Endothelial Cells

Abstract

Villous development and maturation depend on fetoplacental angiogenesis but detailed baseline quantitative data on underlying structural events are lacking. The present aim was to analyse temporospatial patterns of villous and fetal vascular growth using microscopical sections of placentae at different periods of gestation. The emphasis is on acquiring absolute rather than relative data. Random tissue samples collected at 10–41 weeks of gestation were processed for stereological analyses. Growth strategies in ‘stem’, ‘intermediate’ and ‘terminal’ villi (classified according to villous diameter and nature of fetal vessels) were evaluated in terms of total volumes, lengths and mean cross-sectional areas. Total volume, total and relative length, mean cross-sectional area and shape, vascular endothelial cell number and mean cell size (squame surface area) were used to examine capillary growth. Volumes of ‘intermediate’ and ‘terminal’ villi increased significantly due to elongation and thinning. Villous maturation involved differential growth of capillaries which grew linearly without changes in mean cross-sectional area. Longitudinal growth was due to endothelial cell proliferation and increases in mean cell area. Events were characterized by a common inflection point at about mid-gestation. Usually, an early slow growth phase was followed by one of faster growth but capillary:villus length ratios and capillary shape factors tended to peak at mid-gestation. Findings confirm that angiogenesis is linked to villous growth and maturation, and is biphasic with dramatic changes in vascular content and arrangement occurring around mid-gestation. Capillary growth occurs preferentially and is solely by increase in total length driven by continuous proliferation and, later, by endothelial cell remodelling. Though providing no evidence for branching versus non-branching angiogenesis, these observations are consistent with the paradigm that fetoplacental angiogenesis occurs in two phases, the switch being associated with changes in uteroplacental oxygen tensions, local growth factor receptors and their ligands.