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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711652
• 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描述从分子到功能水平改变胎盘生物学的生物学相关暴露，推进对胎盘机制功能的基本理解。