Hypobaric Hypoxia and Villous Trophoblast: Evidence that Human Pregnancy at High Altitude (3600 m) Perturbs Epithelial Turnover and Coagulation-Fibrinolysis in the Intervillous Space

Abstract

Spatial relationships between fibrin-type fibrinoid and regions of villous trophoblast were examined in order to address two main questions: [1] is high-altitude pregnancy accompanied by changes in the sizes of trophoblast compartments (cytotrophoblast, syncytiotrophoblast, denudation sites)?, and [2] do highland placentae differ in the amounts and distribution patterns of perivillous fibrin-type fibrinoid? Placentae were collected from two ethnic groups completing term pregnancies at low (400m above sea level; n=25) and high (3600m; n=45) altitude in Bolivia. Masson trichrome-stained sections were sampled randomly and analysed stereologically to estimate compartment volumes and surfaces. Comparisons were drawn using variance, Chi-squared and contingency table analyses. At high altitude, birthweights were 265g lower and placentas had a larger intervillous space (270 cf 181cm3), less fibrin-type fibrinoid (4.1 cf 8.4cm3 by volume; 2570 cf 4430cm2 by surface area), less villous trophoblast (50 cf 73cm3) and a smaller villous surface (5.6 cf 7.0m2). Volumes were reduced in all syncytiotrophoblast compartments (with and without nuclear aggregations). Cytotrophoblast was maintained and its relative volume increased significantly (from 2.7 to 3.6 per cent of trophoblast volume). Decreases in villous surface area affected primarily thinner (nuclear aggregate-free) regions of syncytium. Regardless of altitude, fibrin-type fibrinoid was deposited non-randomly: it was preferentially located at sites of trophoblast denudation. Although no altitudinal differences in fibrin-type fibrinoid patterns were detected, absolute surfaces were diminished on denuded and thinner regions of trophoblast but not on syncytial knots or bridges. Ethnic differences at low altitude (relatively greater deposits on denudations in Amerindians) were minimized at high altitude. We conclude that pregnancy at high altitude alters the epithelial steady state (towards cytotrophoblast and away from syncytiotrophoblast) and the coagulation-fibrinolysis steady state in the intervillous space (to favour fibrinolysis over coagulation). Thinner regions of syncytiotrophoblast may be the main sites of greater fibrinolytic or anticoagulatory activity. The findings are partly consistent with results from in vitro studies which indicate that hypoxia stimulates proliferation of cytotrophoblast but impairs fusion into syncytium.