Using natural adaptation to drive treatment innovation for altitude-related obstetric complications

利用自然适应推动高原相关产科并发症的治疗创新

基本信息

批准号：
10473514
负责人：
Kathryn Wilsterman
金额：
$ 0.85万
依托单位：
UNIVERSITY OF MONTANA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10473514
关键词：
Academic skills Adult Adverse effects Altitude Andean Automobile Driving Biological Models Birth Chinese Chronic Clinical Data Deer Deer Mouse Development Discipline of obstetrics Disease Environmental Risk Factor Etiology European Evolution Fellowship Fetal Development Fetal Growth Fetal Growth Retardation Fetal health Foundations Gene Expression Profile Genes Genomic approach Genomics Goals Growth Health Histologic Human Hypoxia Immunohistochemistry Indigenous Individual Infant Health Infrastructure Intervention Kansas Laboratory mice Life Mammals Maternal Health Measures Medical Modeling Molecular Montana Morphology Mothers Mouse Strains Outcome Pathologic Pathway interactions Peromyscus Phenotype Physiological Physiology Placenta Placentation Population Pre-Eclampsia Pregnancy Pregnancy Complications Preventive treatment Process Research Resistance Risk Rodent Shapes Structure System Testing Time Tissues Training Universities Variant Vascular remodeling Woman Work base experience experimental study fetal functional genomics functional plasticity gene network gestational hypoxia implantation improved innovation insight novel obstetrical complication preservation prevent pup residence response theories therapy development trait transcriptome transcriptome sequencing transcriptomics

项目摘要

Pregnancies at high altitude (>2500m) are 3–4 times more likely to involve complications, like intrauterine growth restriction and pre-eclampsia, that can have long-term impacts on maternal and infant health. However, indigenous Andeans and Tibetans, who are native to high altitude, do not experience an elevated risk for these complications. Understanding the physiological mechanisms that protect fetal development and maternal health in altitude-adapted populations could help identify targets for clinical intervention or preventative treatment to improve gestational outcomes at altitude. I propose to use an emerging model system for altitude adaptation, the deer mouse (Peromyscus maniculatus), to identify the processes underlying pathological placentation at altitude and the evolutionary adaptations that allow for normal fetal growth at altitude. As in humans, lowland deer mice experience fetal growth restriction under simulated altitude, whereas altitude- adapted deer mice are able to maintain normal fetal growth. In addition, placental adaptations appear to be involved in fetal growth preservation in highlanders. To understand how hypobaric hypoxia and altitude adaptation shape placentation and placental function, I will combine functional genomic analysis of placenta tissue across three gestational time-points with histological and morphological measures of placental and fetal development from lowland and highland deer mice gestating under hypobaric hypoxia. I will also include an outbred laboratory mouse strain in my experiments to identify conserved, placental responses to hypoxia. First, I will differentiate between adaptive and maladaptive structural plasticity in the placenta at altitude using immunohistochemistry. Second, I will generate layer-specific transcriptomes from placentas using RNASeq to identify gene networks and stability therein underlying plastic placentation. The proposed aims will advance our understanding of placentation at altitude and its effects on fetal health, and they will provide new directions for medical intervention by identifying pathways that evolution has adaptively altered. The proposed research will be completed in the Cheviron and Good labs at the University of Montana, which offer complimentary expertise relevant to this project. The Cheviron and Good labs also have the necessary experience and infrastructure through University of Montana to facilitate the comprehensive development of professional and academic skills across the fellowship tenure. Collaborator Dr. Soares at University of Kansas will provide additional intellectual and technical training specific to placentation and hypoxia.

高海拔（> 2500m）的怀孕可能是t的可能性增加3-4倍，但对母亲和婴儿的健康产生了长期影响。对于这些适应高度的人群的戒律和孕妇可以识别临床干预或嘲笑的目标，以影响高空的妊娠结局。在高度的胎儿生长中，高度的胎儿生长在模拟高度下的基础，而高度似乎参与了高地的胎儿生长。将胎盘组织的功能分析与低地和内度小鼠的牙科和胎儿发育的组织学和形态衡量，在我的实验中，我将鉴定自适应和低氧的胎盘反应。胎盘的塑料塑料在使用RNASEQ的胎盘中产生层的特异性转录，以识别胎盘的特定塑料。将通过识别蒙大拿州的E University提供新的干预措施。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Evolution in reproductive tempo and investment across the Peromyscus radiation.

DOI：
10.1002/jez.2666
发表时间：
2023-01
期刊：
JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY
影响因子：
2.8
作者：
Wilsterman, Kathryn;Cunningham, Kirksey
通讯作者：
Cunningham, Kirksey