Genes Related To Placental Adaptation And Their Biological Functions In High-altitude Populations

Part I Strategies of placental adaptation to high altitude among TibetansThe physiological adaptation of pregnant women is often impaired at high altitudes,increasing the risk of low birth weight.However,the severity of decreases in fetal weight due to increased altitude varies among populations.Tibetans are reportedly protected from the altitude-associated reduction in birth weight,partly due to their placental adaptation.However,the placenta’s role in high-altitude adaptation has been scarcely explored by comparing high-altitude Tibetans with other populations.Therefore,we aimed to perform a stereological analysis to understand the structural adaptations of the placenta contributing to the protection of Tibetans against the influence of high-altitude hypoxia on fetal development.The morphology of the placenta among high-altitude Tibetans(n=10)and Caucasians(n=7)was compared and analyzed.We found that the placenta has different high-altitude adaptation strategies between different populations.Moreover,placental efficiency was found to be improved among Tibetans than in Caucasians.This may be attributed to the increased volume of diffusion villi,higher density of diffusion vessel length,and shorter diffusion distance.Part II Differential Genes of Placental Adaptation in High Altitude TibetanThe Tibetan population has lived and successfully reproduced at high altitude for many generations.Studies have shown that Tibetans have various mechanisms for protection against high-altitude hypoxia,which are probably due,at least in part,to placental adaptation.However,comprehensive in silico analyses of placentas in Tibetans are lacking.We performed a microarray-based comparative transcriptome analysis of 10 Tibetan women from Yushu,Qinghai,CHN(~3780 m)and 10 European women living in Leadville,CO,USA(~3100 m)for less than three generations and immunohistochemical method was used to verify the results.Expression of HIF-1α,STAT3,EGFR,HSP5 A,XBP1 and ATF6 A m RNA was less in the Tibetan placentas as compared with European placentas.A total of 38 mi RNAs were involved in regulating these genes.Differentially expressed genes were enriched for HIF1α signaling pathways,protein processing in the endoplasmic reticulum,PI3K-AKT signaling pathways,and MAPK signaling pathways.Based on the transcriptome profiles,the Tibetan population was distinct from the European population;placental tissues from the Tibetan population are lacking hypoxic responses,and "passivation"occurs in response to hypoxic stress.These results provide insights into the molecular signature of adaptation to high altitudes in these two populations.Part III Placental Structure Adaptation in High Altitude MongolianThe physiological adaptation of pregnant women is often impaired at high altitudes,increasing the risk of low birth weight.However,the severity of decreases in fetal weight due to increased altitude varies among populations.Tibetans are reportedly protected from the altitude-associated reduction in birth weight,partly due to their placental adaptation.However,the placenta’s role in high-altitude adaptation has been scarcely explored by comparing high-altitude Tibetans with other populations.Therefore,we aimed to perform a stereological analysis to understand the structural adaptations of the placenta contributing to the protection of Tibetans against the influence of high-altitude hypoxia on fetal development.The morphology of the placenta among high-altitude Tibetans(n=6)and Mongolian(n=6)was compared and analyzed.We found that the placenta has different high-altitude adaptation strategies between different populations.Moreover,placental efficiency was found to be improved among Tibetans than in Mongolians.This may be attributed to the increased volume of diffusion villi.High-altitude Mongolians maintains the same fetal weight as Tibetan population by increasing the length and surface area of the diffusion vessels to supplement the oxygen and nutrition of the fetus and placenta.Our results provide practical evidence to explain the mechanisms of placental adaptation in hypoxic patients.