Physiological determinants of reproductive success: a paradigm for understanding the ways in which genes influence adaptation to high altitudes

摘要

Populations have resided at high altitudes for different lengths of time. While there is widespread belief that "adaptation" of long-resident Tibetans or Andeans has occurred, the genetic factors and physiological processes involved are unclear. Anecdotal reports suggest that high-altitude newcomers, historically as well as today, experience increased complications of pregnancy and fetal life. An altitude-associated increase in the frequency of intrauterine growth restriction (IUGR) and preeclampsia may also contribute to the altitude-related rise in infant mortality present in Bolivia today. To address whether genetic factors were involved in this altitude-related reduction in birth weight, we compared birth weights of babies born to parents with Andean (Aymara/Quechua), mestizo, or foreign (largely European) surnames across an altitude range of 300 to 4100 m. Babies bom to Andean women experienced less IUGR than those born to Europeans at 3600 m but not at 300 m. To test the hypothesis that Andean women delivered more oxygen to the uteroplacental circulation than the European women, we are measuring determinants of arterial oxygenation and uterine blood flow in Andean and foreign residents of 3600 m throughout pregnancy and again postpartum for a measurement in the nonpregnant state. During pregnancy, Andean and European women have similar levels of arterial oxygen saturation but arterial oxygen content is lower in the Andean subjects as the result of lower hemoglobin levels near term. The Andean compared to the European women appear to have higher cardiac outputs, as judged by common iliac blood flow, and greater uterine artery diameters and blood flow, suggesting more oxygen is being delivered to the uteroplacental circulation. Foreign babies are smaller in utero (by ultrasound) with umbilical and middle cerebral artery ratios suggestive of exaggerated fetal hypoxia. We speculate that such physiological adaptations may not only be adaptive during pregnancy/fetal life but also, via "fetal programming" against later-in-life complications of systemic and pulmonary hypertension. Further study is required to identify the specific genes involved. (Supported in part by NIH grants TW01188, HL60131).