Characterization of placenta dynamics and response to various metabolic exposures

胎盘动力学特征和对各种代谢暴露的反应

• 批准号: RGPIN-2017-05457
• 负责人: Adamo, Kristi
• 金额: $ 1.82万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=643445
• 关键词: Characterization; placenta; dynamics; response; various

The long-term aim of my research program is to advance the basic understanding of the mechanistic functionality of the placenta, by identifying and characterizing biologically relevant exposures which alter placental biology at the molecular through to functional level.******In Eutherian mammals, the placenta has evolved to become the physiological and metabolic link between mother and her offspring. Despite its integral role in sustaining new life, it is the least understood and least studied of all mammalian organs. The placenta, embedded in the uterine wall, is tethered by the umbilical cord to the fetus and acts as the interface of nutrient and oxygen transport, eliminates waste, regulates fetal temperature and produces hormones that promote appropriate maternal adaptation to pregnancy. Examining the response to challenges or the potential differences in form and function with varying environmental conditions (exercise or high energy expenditure for this program of research) in placenta tissue models is a highly novel research area.******My team is interested in the impact of maternal energy expenditure on fundamental aspects of placenta biology. We hypothesize that the increases in energy expenditure that accompany exercise result in changes within the placenta related to vascular development and reactivity, substrate metabolism and mitochondrial form and function. The specific mechanisms underlying the optimized development and function of the placenta remain unknown. One mechanistic pathway through which maternal exercise may influence placenta biology is the myokine secretome – a collection of cytokines and small peptides secreted from contracting skeletal muscle, capable of paracrine and endocrine function. Since the placenta is the only mammalian organ that serves a vital function before exhausting its usefulness, it offers a large tissue repository to be leveraged for studies. In the proposed program of research one of our short-term objectives is to compare mechanistic functionality using 3rd trimester placenta explants, collected from women at the extreme ends of the energy expenditure spectrum (high vs. low EE) across pregnancy (AIM 1). An additional short-term objective is to determine the specific contributions of myokine exposure, as biologically relevant stimuli mimicking exercise, on critical aspects of placenta biology using an ex vivo, 1st and 3rd trimester human placenta tissue explant model (AIM 2). ******IMPACT statement: Even though the placenta is arguably the most important life-supporting organ, we know very little about it. Understanding placenta function is thus critical as it impacts fetal phenotype and long-term physiological and metabolic development. Biologically, it is a fascinating tissue due to its rapid growth and subsequent demise along with its extremely broad range of functions.

我的研究计划的长期目标是通过识别和表征在分子水平上改变胎盘生物学的生物学相关暴露，以促进对胎盘机械功能的基本理解。在真兽目哺乳动物中，胎盘已经进化成为母亲和她的后代之间的生理和代谢联系。 尽管它在维持新生命中起着不可或缺的作用，但它是所有哺乳动物器官中了解和研究最少的。 胎盘嵌入子宫壁，通过脐带与胎儿相连，作为营养和氧气运输的界面，消除废物，调节胎儿温度并产生促进母体适当适应妊娠的激素。在胎盘组织模型中检查对挑战的反应或在不同环境条件下形式和功能的潜在差异（本研究计划的运动或高能量消耗）是一个非常新颖的研究领域。我的团队对母体能量消耗对胎盘生物学基本方面的影响感兴趣。我们推测，伴随运动的能量消耗增加导致胎盘内与血管发育和反应性、底物代谢和线粒体形式和功能相关的变化。胎盘优化发育和功能的具体机制仍不清楚。母体运动可能影响胎盘生物学的一个机制途径是肌因子分泌体-收缩骨骼肌分泌的细胞因子和小肽的集合，能够旁分泌和内分泌功能。由于胎盘是哺乳动物中唯一一个在耗尽其效用之前发挥重要作用的器官，因此它提供了一个大型组织库，可用于研究。在拟议的研究计划中，我们的短期目标之一是使用妊娠晚期胎盘外植体比较机械功能，这些胎盘外植体是从整个妊娠期间能量消耗谱（高与低EE）极端的女性中收集的（AIM 1）。另一个短期目标是使用离体、第1和第3个三个月人胎盘组织外植体模型（AIM 2）确定肌因子暴露作为模拟运动的生物学相关刺激对胎盘生物学关键方面的具体贡献。** 影响声明：尽管胎盘可以说是最重要的生命支持器官，但我们对其知之甚少。因此，了解胎盘功能至关重要，因为它影响胎儿表型和长期生理和代谢发育。从生物学上讲，它是一种迷人的组织，因为它的快速生长和随后的死亡沿着其极其广泛的功能。