Effect of high altitude on human placental amino acid transport.
Effect of high altitude on human placental amino acid transport.
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高海拔对人胎盘氨基酸转运的影响。
DOI：
10.1152/japplphysiol.00691.2019
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Jansson,Thomas
中科院分区：
文献类型：
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作者：
Vaughan,OwenR;Thompson,Fredrick;Lorca,RamónA;Julian,ColleenG;Powell,TheresaL;Moore,LornaG;Jansson,Thomas
生活在高海拔地区的妇女所生婴儿的出生体重低于生活在海平面地区的妇女。出生体重与胎盘系统A介导的氨基酸运输能力有关，严重的环境缺氧会降低离体滋养细胞和小鼠胎盘中系统A的活性。然而，高海拔对人胎盘氨基酸运输的影响尚不清楚。我们假设高海拔地区女性胎盘的微绒毛膜（MVM）系统A和系统L氨基酸转运蛋白活性低于低海拔地区女性。在计划的无产剖宫产术后，从居住在高海拔地区（HA; bb0 2500 m;n= 14）或低海拔地区（LA; < 1700 m;n= 14）的健康孕妇中收集足月胎盘。HA妊娠组出生体重（2.88±0.11 kg）比LA妊娠组（3.30±0.07 kg，P< 0.01）低13%，胎盘重量未见下降。通过免疫印迹测定，HA胎盘的MVM促红细胞生成素受体丰度高于LA胎盘，这与HA胎盘的低氧水平一致。然而，海拔对MVM系统A或L活性没有影响，分别由Na+依赖性[14C]甲基胺异丁酸摄取和[3H]亮氨酸摄取测定。葡萄糖转运蛋白（GLUTs） 1和4以及基底膜GLUT4的MVM丰度在LA和HA胎盘中也相似。居住在高海拔地区的妇女新生儿的低出生体重并不是胎盘氨基酸运输能力降低的结果。这些观察结果与低海拔IUGR婴儿的研究基本一致，其中MVM系统A活性仅在生长受限的婴儿中下调，并有明显的损害。在高海拔地区出生的婴儿比在海平面出生的婴儿小。出生体重取决于子宫内的生长，进而取决于胎盘的营养运输。我们测定了从居住在低海拔和高海拔地区的妇女收集的胎盘的氨基酸运输能力。海拔高度不影响系统A氨基酸在合胞滋养细胞微绒毛膜上的转运，这表明胎盘氨基酸转运受损不会导致高海拔人群出生体重的降低。
Women residing at high altitudes 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 with low-altitude controls. Placentas were collected at term from healthy pregnant women residing at high altitude (HA; >2,500 m;n= 14) or low altitude (LA; <1,700 m;n= 14) following planned, unlabored cesarean section. Birth weight, but not placenta weight, was 13% lower in HA pregnancies (2.88 ± 0.11 kg) compared with LA (3.30 ± 0.07 kg,P< 0.01). MVM erythropoietin receptor abundance, determined by immunoblot, was greater in HA than in 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 downregulated only in growth-restricted babies with significant compromise.NEW & NOTEWORTHYBabies born at high altitude are smaller than at sea level. Birth weight is dependent on growth in utero and, in turn, placental nutrient transport. We determined amino acid transport capacity in placentas collected from women resident at low and high altitude. Altitude did not affect system A amino acid transport across the syncytiotrophoblast microvillous membrane, suggesting that impaired placental amino acid transport does not contribute to reduced birth weight in this high-altitude population.