Moore Lorna G
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, USA.
Reproduction. 2021 Jan;161(1):F81-F90. doi: 10.1530/REP-20-0349.
High altitude offers a natural laboratory for studying the effects of chronic hypoxia on reproductive health. Counter to early accounts, fertility (the number of livebirths) appears little affected although stillbirths are more common. Birth weights are lower due to fetal growth restriction, not shortened gestation. Multigenerational (Andean or Tibetan) compared with newcomer residents appear relatively protected from pregnancy loss as well as altitude-associated fetal growth restriction, perhaps due in part to preservation of the normal rise in uterine artery blood flow. Myometrial artery vasodilator response, a key determinant of uterine blood flow, is blunted in healthy Colorado high-altitude residents, similar to what occurs in intrauterine growth restriction or preeclampsia at low altitude. The high-altitude vessels are also more sensitive to the vasodilatory actions of AMP kinase (AMPK) activation. The gene region containing PRKAA1 (coding for AMPK's alpha-1 catalytic subunit) has been acted upon by natural selection in Andeans and is related to preservation of normal blood flow and fetal growth at high altitude, suggesting one mechanism by which high-altitude adaptation may have been achieved. Preeclampsia is more common at high altitudes but unknown is whether multigenerational residents are protected relative to newcomers. Postnatal loss is diminished in Tibetans vs Han with equal access to health care, perhaps due in part to better maintained arterial O2 saturation during infancy. Finally, pregnancy and intrauterine development not only affect immediate survival but also susceptibility to the later-in-life cardiovascular disease, chronic mountain sickness.
高海拔地区为研究慢性缺氧对生殖健康的影响提供了一个天然实验室。与早期的报道相反，生育率（活产数量）似乎受影响较小，尽管死产更为常见。由于胎儿生长受限，出生体重较低，但妊娠期并未缩短。与新居民相比，多代居住在安第斯山脉或西藏的居民似乎相对不易出现妊娠丢失以及与海拔相关的胎儿生长受限，这可能部分归因于子宫动脉血流正常增加得以保留。子宫肌层动脉血管舒张反应是子宫血流的关键决定因素，在健康的科罗拉多高海拔居民中减弱，类似于低海拔地区宫内生长受限或先兆子痫时的情况。高海拔血管对AMP激酶（AMPK）激活的血管舒张作用也更敏感。包含PRKAA1（编码AMPK的α-1催化亚基）的基因区域在安第斯人群中受到自然选择作用，并且与高海拔地区正常血流和胎儿生长的维持有关，这提示了一种可能实现高海拔适应的机制。先兆子痫在高海拔地区更为常见，但多代居民相对于新居民是否受到保护尚不清楚。在获得同等医疗保健的情况下，藏族与汉族相比，产后损失减少，这可能部分归因于婴儿期动脉血氧饱和度维持得更好。最后，妊娠和宫内发育不仅影响即时生存，还影响日后患心血管疾病、慢性高山病的易感性。
