Adaptive structural and functional evolution of the placenta protects fetal growth in high-elevation deer mice.
Adaptive structural and functional evolution of the placenta protects fetal growth in high-elevation deer mice.
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DOI：
10.1073/pnas.2218049120
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发表时间：
2023-06-20
影响因子：
11.1
通讯作者：
Cheviron, Zachary A.
中科院分区：
文献类型：
--
作者：
Wilsterman, Kathryn;Moore, Emily C.;Schweizer, Rena M.;Cunningham, Kirksey;Good, Jeffrey M.;Cheviron, Zachary A.
居住在高海拔地区与高风险怀孕和低出生体重有关，但其原因机制仍然知之甚少。使用高海拔适应的啮齿动物模型，我们调查了解释低氧环境中胎儿生长轨迹的生理特征，以及进化适应如何改变这些特征。我们发现，在妊娠低氧期间，高海拔和低海拔鹿鼠群体对胎儿生长受限的敏感性不同，这些群体水平的差异与胎盘的结构和转录变化有关。我们进一步将胎盘基因的表达与高海拔地区的选择下的基因组特征联系起来。我们的发现确定了可能与抵消低氧对哺乳动物胎儿和胎盘发育的影响有关的适应。环境低氧挑战胎盘哺乳动物的雌性生殖生理，增加妊娠并发症的发生率。对高海拔的适应限制了许多对人类和其他哺乳动物的影响，提供了对导致和预防与缺氧相关的妊娠并发症的发育过程的潜在洞察。然而，由于缺乏将当地适应人群中妊娠发育的功能、调节和遗传基础联系起来的实验工作，我们对这些适应的理解一直受到阻碍。在这里，我们剖析了鹿小鼠的生殖生理中的高海拔适应，这是一种具有异常广泛的海拔分布的啮齿动物，已成为低氧适应的模型。通过实验习服，我们发现，低地小鼠在受到妊娠低氧的挑战时，会经历明显的胎儿生长受限，而高地小鼠则通过扩大胎盘的隔室来维持正常的生长，这有助于孕母和胎儿之间的营养和气体交换。然后，我们使用隔室特异的转录组分析来表明，胎盘适应性结构重塑与同一隔室内基因表达的广泛变化是一致的。鹿鼠体内与胎儿生长相关的基因与人类胎盘发育相关的基因显著重叠，表明这些过程背后存在保守或收敛的途径。最后，我们用来自自然种群的遗传数据覆盖我们的结果，以确定有助于这些胎盘适应的候选基因和基因组特征。总的来说，这些实验通过揭示在母体低氧下塑造胎儿生长轨迹的生理和遗传机制，促进了我们对低氧环境适应的理解。
Residence at high elevations is associated with higher-risk pregnancies and low birth weight, yet the causal mechanisms remain poorly understood. Using a high elevation-adapted rodent model, we investigated the physiological traits that explain fetal growth trajectories in low-oxygen environments, and how evolutionary adaptation has modified these traits. We showed that high- and low-elevation populations of deer mice differ in their susceptibility to fetal growth restriction during gestational hypoxia and that these population-level differences are associated with structural and transcriptomic changes in the placenta. We further link placental gene expression to genomic features under selection at high elevation. Our findings identify adaptations that are likely relevant to offsetting the effects of hypoxia on fetal and placental development across mammals. Environmental hypoxia challenges female reproductive physiology in placental mammals, increasing rates of gestational complications. Adaptation to high elevation has limited many of these effects in humans and other mammals, offering potential insight into the developmental processes that lead to and protect against hypoxia-related gestational complications. However, our understanding of these adaptations has been hampered by a lack of experimental work linking the functional, regulatory, and genetic underpinnings of gestational development in locally adapted populations. Here, we dissect high-elevation adaptation in the reproductive physiology of deer mice (Peromyscus maniculatus), a rodent species with an exceptionally broad elevational distribution that has emerged as a model for hypoxia adaptation. Using experimental acclimations, we show that lowland mice experience pronounced fetal growth restriction when challenged with gestational hypoxia, while highland mice maintain normal growth by expanding the compartment of the placenta that facilitates nutrient and gas exchange between gestational parent and fetus. We then use compartment-specific transcriptome analyses to show that adaptive structural remodeling of the placenta is coincident with widespread changes in gene expression within this same compartment. Genes associated with fetal growth in deer mice significantly overlap with genes involved in human placental development, pointing to conserved or convergent pathways underlying these processes. Finally, we overlay our results with genetic data from natural populations to identify candidate genes and genomic features that contribute to these placental adaptations. Collectively, these experiments advance our understanding of adaptation to hypoxic environments by revealing physiological and genetic mechanisms that shape fetal growth trajectories under maternal hypoxia.
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