Browne Vaughn A, Julian Colleen G, Toledo-Jaldin Lillian, Cioffi-Ragan Darleen, Vargas Enrique, Moore Lorna G
Department of Emergency Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Philos Trans R Soc Lond B Biol Sci. 2015 Mar 5;370(1663):20140068. doi: 10.1098/rstb.2014.0068.
Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100-4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success.
两足行走和大脑扩张所需的进化权衡影响子宫动脉(UtA)血流的孕期增加,进而影响生殖成功。我们通过回顾其决定因素并展示来自191名血压正常(正常,n = 125)或高血压(先兆子痫(PE)或妊娠期高血压(GH),n = 29)的安第斯居民的数据,来考量UtA血流的重要性,这些居民生活在海拔非常高(4100 - 4300米)或低海拔(400米,n = 37)地区。先前的研究表明,子宫内生长受限(IUGR)的妊娠中UtA血流减少,但IUGR是否由由此导致的胎儿缺氧引起尚不清楚。我们发现,与低海拔地区的血压正常女性相比,高海拔地区血压正常女性的UtA血流和胎儿缺氧的多普勒指数更高,但胎儿生长情况相似。早发型PE患者的UtA血流明显低于高海拔地区的正常女性,并且她们的胎儿更缺氧,表现为胎儿心率更低、多普勒指数更低以及IUGR更严重。我们得出结论,尽管胎儿缺氧更严重,但高海拔地区正常安第斯人的较高UtA血流很好地保障了胎儿生长,然而,早发型PE患者的UtA血流降低会加剧胎儿缺氧,导致胎儿通过降低心输出量和重新分配血流做出反应,以帮助维持大脑发育,而牺牲其他部位的生长。我们推测,UtA血流不仅是一条重要的供应线,也是刺激调节胎儿 - 胎盘代谢和生长的代谢及其他过程的触发因素。利用高海拔这个天然实验室进行的研究,对于确定人类生殖成功所涉及的生理和遗传机制具有重要价值。