RESPONSE OF HUMAN TROPHOBLAST TO HYPOXIA: MORPHOLOGY, GLUCOSE TRANSPORT AND METABOLISM, ENDOCRINE SYNTHESIS. † 1230

Placental hypoxia is considered a feature of diverse clinical entities including IUGR, preeclampsia and cocaine abuse. We have compared human trophoblast in culture maintained in normoxia, (N, p0₂ 120 mm Hg) to trophoblast in hypoxia, (H, p0₂ 12 mm Hg). Trophoblast survives >72 hours of H, retaining its ability to synthesize metabolically labeled proteins with a gel electrophoretic pattern very similar to trophoblast in N. Maturation of isolated cytotrophoblast, however, is inhibited: apical microvilli are sparse and blunted, Ki 67 proliferation antigen is higher than in N consistent with an interruption in cell cycle, and hCG synthesis does not increase progressively. Steady state mRNA levels for hCG are also reduced. Synthesis of hPL, estrogen and progesterone decrease >90% in H; ACTH is unaffected. Uptake of [³H]2-deoxyglucose is reduced 90%. Lineweaver-Burk plots suggest two transporters with Vmax of both reduced in H and Km essentially unchanged. Paradoxically glucose consumption increases two-fold, steady state mRNA levels of GLUT1, three-fold, and GLUT3, ten-fold. Following return to N, uptake of [³H]2-DG is restored to normal within 10 minutes. Further studies are indicated to resolve these apparent contradictions.