EFFECT OF HIGH ALTITUDE ON HUMAN PLACENTAL AMINO ACID TRANSPORT.

Women residing at high altitude deliver infants of lower birth weight than at sea-level. Birth weight correlates with placental System A-mediated amino acid transport capacity and severe environmental hypoxia reduces System A activity in isolated trophoblast and the mouse placenta. However, the effect of high altitude on human placental amino acid transport remains unknown. We hypothesized that microvillous membrane (MVM) System A and System L amino acid transporter activity is lower in placentas of women living at high altitude, compared to low altitude controls. Placentas were collected, at term, from healthy pregnant women residing at high altitude (HA, >2500m, n=14) or low altitude (LA, <1700m, n=14), following planned, unlabored cesarean section. Birth weight, but not placenta weight, was 13% lower in HA pregnancies (2.88±0.11kg) compared to LA (3.30±0.07kg, P<0.01). MVM erythropoietin receptor abundance, determined by immunoblot, was greater in HA than LA placentas, consistent with lower placental oxygen levels at HA. However, there was no effect of altitude on MVM System A or L activity, determined by Na+-dependent 14C-methylaminoisobutyric acid uptake and 3H-leucine uptake, respectively. MVM abundance of glucose transporters (GLUTs) 1 and 4, and basal membrane GLUT4, were also similar in LA and HA placentas. Low birth weights in the neonates of women residing at high altitude are not a consequence of reduced placental amino acid transport capacity. These observations are in general agreement with studies of IUGR babies at low altitude, in which MVM System A activity is down-regulated only in growth restricted babies with significant compromise.

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