Villous trophoblast growth in pregnancy at high altitude

Abstract

The trophoblastic epithelium of placental villi exhibits continuous turnover. Phases of proliferation, recruitment, maturation, terminal differentiation (apoptosis) and extrusion exist in steady state and occur in distinctive spatial compartments, viz. cytotrophoblast cells (CT), syncytiotrophoblast (ST), syncytial knots (SK), denudation sites (DEN) and syncytial fragments. Hypoxia in vitro stimulates CT proliferation but inhibits recruitment into ST. Pregnancy at high altitude (HA) is associated with reduced birthweight and provides a convenient model of preplacental (hypobaric) hypoxia. HA placentas show impoverished villous growth and changes in the incidences of CT cells and SK regions. Here we examine placentas from Amerindian and nonindigenous women who completed full‐term pregnancies at low altitude (LA; 400 m; n = 25) and high altitude (HA; 3600 m; n = 45) in Bolivia. We test the hypothesis that HA pregnancy disturbs the epithelial steady state as reflected in the relative volumes and surfaces of trophoblast compartments. Masson trichrome stained tissue sections and microscopical fields were generated by uniform random sampling. Point and intersection counts were used to estimate the volumes and surface areas of nonsyncytial knots (nonSK), SK regions, syncytial bridges (SB) and denudation sites (DEN). Absolute values were compared by 2‐way analyses of variance to resolve altitudinal from ethnic effects. At LA, trophoblast comprised about 85% nonSK, 8% SK, 5% SB and 3% CT by volume. Its maternal surface area comprised about 91% nonSK, 5% SK, 2% SB, and 3% DEN. Apart from CT (the fractional volume of which increased to 4%, P < 0.05), relative volumes of trophoblast compartments did not alter significantly at HA. However, there was a roughly 30% reduction in absolute volume of trophoblast at HA (P < 0.001) which could be explained mainly by a decrease in volume of nonSK regions (P < 0.001). The volume of CT was unaltered. Absolute surface areas of villi also declined at HA (by 20%, P < 0.01) and, again, this was attributed mainly to nonSK. The findings confirm that poor villous growth is partly due to failure of trophoblast to attain the growth seen at LA. The reduced trophoblastic growth occurs despite an increase in relative volume of CT cells (consistent with previously reported increases in proliferative activity) and, probably, by a combination of compromised syncytial fusion and continuing extrusion of syncytial fragments.