Uteroplacental Vasculature and Fetal Growth after Plastic Particle Exposure

塑料颗粒暴露后的子宫胎盘脉管系统和胎儿生长

基本信息

批准号：
10677264
负责人：
Chelsea Cary
金额：
$ 4.29万
依托单位：
RUTGERS BIOMEDICAL AND HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10677264
关键词：
Adult Adverse effects Affect Air Air Pollution Animals Area Arteries Biological Biology Blood Blood Vessels Blood flow Cardiometabolic Disease Cardiovascular system Cell physiology Data Development Diffusion Disease Distal Endothelial Cells Endothelium Exposure to Fellowship Female Fetal Development Fetal Growth Fetal Growth Retardation Fetal Tissues Fetal Weight Fetus General Population Grant Growth Health Hour Human Immunohistochemistry Impairment Inhalation International Intervention Invaded Knowledge Laboratories Labyrinth Lung Maternal-Fetal Exchange Measures Mechanics Mediator Modeling Molecular Target Morphogenesis Mothers Myography NOS3 gene Nitric Oxide Nutrient Nylons Occupational Exposure Organ Oxygen Particulate Matter Pathway interactions Perinatal mortality demographics Physiology Placenta Placentation Plastics Predisposition Pregnancy Pregnant Women Principal Investigator Process Rattus Research Risk Assessment Signal Transduction Site Smooth Muscle Myocytes Spiral Artery of the Endometrium Structure Structure of parenchyma of lung Surface Techniques Testing Therapeutic Intervention Tissues Toxicology Training Translating Uterus Vascular Smooth Muscle Vasodilation Vulnerable Populations Weight air filter angiogenesis arteriole biomass fuel cardiometabolic risk constriction endothelial dysfunction hemodynamics indoor particulate matter infant morbidity infant morbidity/mortality intravital microscopy migration nanoparticle particle particle exposure pharmacologic pregnant pressure protein expression radial artery reproductive targeted treatment therapeutic target tool

项目摘要

PROJECT SUMMARY/ABSTRACT In humans, fetal growth restriction (FGR) and impaired placental development are associated with infant morbidity and mortality and susceptibility to adulthood diseases. In pregnant animals, inhalation of particles alters the functionality of the uteroplacental vasculature, leading to impaired placental and fetal growth. Particulate matter (PM) can target the uteroplacental vasculature in multiple ways. One way by which particles can disrupt the uteroplacental vasculature is by impairing vasodilation. During pregnancy, uterine vessels must be sensitive to vasodilation mediators to meet the dynamic needs of the placenta and fetus. Central to this vasoreactivity is the endothelial cell that translates signals from the blood to the vascular smooth muscle cells, leading to vessel dilation or constriction. Additionally, the placenta is a critical organ for the diffusion of oxygen and transport of nutrients to the developing fetus. PM can impair development of the placental vasculature that allows for maternal-fetal exchange and decrease the ratio of placental-to-fetal tissue, known as placental efficiency. Our laboratory recently showed that plastic particles can translocate through the placenta to the fetus after pulmonary exposure, suggesting that the particles directly interact with the uteroplacental vasculature. The environmental burden of plastics is exponentially increasing. Micro’ nanoplastics (MNPs) represent a ubiquitous exposure concern for the general population and for vulnerable groups, such as pregnant women, it is important to elucidate how MNP inhalation may affect fetal development. These particles are generated and suspended in the air by the combustion of bulk plastic or through slower processes like mechanical degradation where a bulk plastic fragments into small pieces in the microparticle (>100 nm) and nanoparticle (<100 nm) size range. Our preliminary data demonstrates that MNP inhalation in virgin female rats disrupts uterine vascular reactivity. Furthermore, using a pregnancy model of MNP inhalation throughout gestation, we observed FGR, increased placental weight, and decreased placental efficiency suggesting the placenta is a target organ of MNPs in rats. Therefore, the central hypothesis of this proposal is that maternal inhalation of MNP throughout gestation decreases placental efficiency by impairing uterine vasodilation and disrupting development of the placental vasculature in rats. The aims in this proposal will investigate the mechanisms by which repeated maternal MNP inhalation dysregulates the uterine vasculature and placental development, thus contributing to FGR. Aim 1 will identify mechanisms of impaired uterine vascular reactivity and how endothelial cell function is altered after maternal MNP exposure. Aim 2 will determine how maternal MNP inhalation modifies development of the placental vasculature using histopathological analyses and immunohistochemistry. This research will identify mechanisms of MNP induced FGR and present potential targets for therapeutic intervention. By completing the proposed research, courses, and training the Principal Investigator will be trained independently conduct state- of-the-art experimental techniques and carry out cardiovascular and reproductive toxicological research.

项目概要/摘要在人类中，胎儿生长受限（FGR）和胎盘发育受损与婴儿吸入颗粒会改变怀孕动物的发病率和死亡率以及对成年疾病的易感性。子宫胎盘脉管系统的功能，导致胎盘和胎儿生长受损。物质 (PM) 可以通过多种方式靶向子宫胎盘脉管系统，这是粒子破坏的一种方式。子宫胎盘脉管系统是通过损害血管舒张而产生的。在怀孕期间，子宫血管必须是敏感的。血管舒张介质以满足胎盘和胎儿的动态需求是这种血管反应性的核心。内皮细胞将信号从血液翻译至血管平滑肌细胞，从而导致血管此外，胎盘是氧气扩散和运输的关键器官。胎儿发育所需的营养物质会损害胎盘脉管系统的发育。母胎交换并降低胎盘与胎儿组织的比率，称为胎盘效率。实验室最近表明，塑料颗粒在肺部感染后可以通过胎盘转移到胎儿体内。暴露，表明颗粒直接与子宫胎盘血管系统相互作用。塑料的负担正在呈指数级增加。微型纳米塑料（MNP）代表着无处不在的暴露。考虑到普通民众和孕妇等弱势群体，重要的是阐明吸入 MNP 如何影响胎儿发育。通过散装塑料的燃烧或通过机械降解等较慢的过程（其中散装塑料）我们的塑料碎片可分为微米颗粒（>100 nm）和纳米颗粒（<100 nm）尺寸范围内的小块。初步数据表明，处女雌性大鼠吸入 MNP 会破坏子宫血管反应性。此外，使用整个妊娠期间吸入 MNP 的妊娠模型，我们观察到 FGR、增加胎盘重量和胎盘效率降低表明胎盘是大鼠 MNP 的靶器官。因此，该提案的中心假设是母亲在整个妊娠期间吸入 MNP 通过损害子宫血管舒张和破坏胎盘发育来降低胎盘效率本提案的目的是研究重复母体 MNP 的机制。吸入会导致子宫脉管系统和胎盘发育失调，从而导致 FGR 目标 1。确定子宫血管反应性受损的机制以及术后内皮细胞功能如何目标 2 将确定母体 MNP 吸入如何改变胎儿的发育。这项研究将使用组织病理学分析和免疫组织化学来识别胎盘脉管系统。通过完成 MNP 诱导 FGR 的机制并提出治疗干预的潜在目标。拟议的研究、课程和培训首席研究员将接受独立培训，进行国家- 最先进的实验技术并开展心血管和生殖毒理学研究。