Abstract:
High altitude (HA) hypoxia lowers uterine artery (UtA) blood flow during pregnancy and birth weight. Adenosine monophosphate kinase (AMPK) activation has selective, uteroplacental vasodilator effects which lessen hypoxia-associated birth weight reductions. In this study, we determined the relationship between AMPK-pathway gene expression and metabolites in the maternal circulation during HA pregnancy as well as with the maintenance of UtA blood flow and birth weight at HA. HA (2793 m) vs low altitude (LA; 1640 m) residents had smaller UtA diameters at weeks 20 and 34, lower UtA blood flow at week 20, and lower birth weight babies. At week 34, HA vs LA women had decreased expression of up- and down-stream AMPK-pathway genes. Expression of the a-1 AMPK catalytic subunit, PRKAA1, correlated positively with UtA diameter and blood flow at week 20 (HA) and 34 (LA). Downstream AMPK-pathway gene expression positively correlated with week 20 fetal biometry at both altitudes and with UtA diameter and birth weight at LA. Reduced gene expression of AMPK activators and downstream targets in HA versus LA women, together with positive correlations between PRKAA1 gene expression, UtA diameter, and blood flow suggest that greater sensitivity to AMPK activation at mid-gestation at HA may help offset later depressant effects of hypoxia on fetal growth.
摘要:
高海拔(HA)缺氧会降低妊娠和出生体重期间的子宫动脉(UtA)血流量。腺苷一磷酸激酶(AMPK)的激活具有选择性,子宫胎盘血管舒张作用,减轻缺氧相关的出生体重减轻。在这项研究中,我们确定了HA妊娠期间母体循环中AMPK途径基因表达与代谢物之间的关系,以及与维持HA时UtA血流和出生体重之间的关系。HA(2793m)与低海拔(LA;1640m)居民在第20周和第34周的UtA直径较小,第20周的UtA血流量较低,出生体重较低。在第34周时,HA和LA女性的上游和下游AMPK途径基因的表达降低。α-1AMPK催化亚基的表达,PRKAA1与第20周(HA)和第34周(LA)的UtA直径和血流量呈正相关。AMPK途径下游基因表达与两个海拔高度的20周胎儿生物特征呈正相关,与LA的UtA直径和出生体重呈正相关。与LA女性相比,HA中AMPK激活剂和下游靶标的基因表达降低,与PRKAA1基因表达呈正相关,UTA直径,和血流表明,在妊娠中期,HA对AMPK激活的更高敏感性可能有助于抵消缺氧对胎儿生长的抑制作用。