Changes in Fetal Capillaries During Preplacental Hypoxia: Growth, Shape Remodelling and Villous Capillarization in Placentae from High-Altitude Pregnancies

Abstract

Patterns of fetoplacental angiogenesis and villous growth vary in pregnancies complicated by different forms of fetal hypoxia. This study uses stereological estimators to examine absolute and relative dimensions of villi and fetal capillaries in cases of preplacental hypoxia due to pregnancy at high altitude. Placental samples were drawn from well-defined subjects in different ethnic groups born, raised and completing term pregnancies at low (500m) and high altitude (3600m above sea level). Volumes, surfaces and lengths were used to monitor the nett growth of villi and capillaries. Indices of villous capillarization comprised volume, surface and length densities and capillary:villus surface and length ratios. Villus/capillary ‘calibre’ and shape were quantified using cross-sectional areas, perimeters and shape coefficients (perimeter2/area). Group comparisons were drawn by two-way analyses of variance with altitude and ethnicity as the main factors. Volumes, surfaces and lengths of villi, and volumes of capillaries, were reduced at high altitude. Capillary volume declined primarily by formation of narrower microvessels which were more irregular in outline. There were no differences in capillary surface area or length. Cross-sectional sizes and shapes of villi were unaltered. Differences in villous capillarization were confined to higher surface and length densities. Ethnic differences in villous length, capillary length and cross-sectional area tended to favour native groups who are pre-adapted to life at high altitude. Results show that high-altitude pregnancy is not accompanied by increased angiogenesis but may involve enhanced villous capillarization and vascular shape remodelling. Comparisons are drawn with changes seen in maternal anaemia. It is concluded that absolute and relative measures of villous and capillary growth are required lest misinterpretations are introduced by equating hypercapillarization with enhanced angiogenesis or the pattern of capillary branching. The importance of controlling for various potential confounders is also emphasized.