Detecting biochemical changes in the pregnant mouse cervix by Raman spectroscopy

拉曼光谱检测妊娠小鼠子宫颈的生化变化

基本信息

批准号：
8766404
负责人：
Anita Mahadevan-Jansen
金额：
$ 38.74万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-10 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8766404
关键词：
Address Algorithms Alprostadil Amides Amino Acids Applications Grants Biochemical Biochemical Markers Biochemistry Biological Biological Markers Biological Sciences Biology Biomechanics Biomedical Engineering Birth Cervical Cervical Ripening Cervix Uteri Classification Clinical Collaborations Collagen Computational algorithm Computer Analysis Data Detection Development Disease Early Diagnosis Early treatment Elasticity Emerging Technologies Etiology Fetal Development Fiber Optics Foundations Generations Goals Health High-Risk Pregnancy Hormonal Hour Hydration status Image Immunohistochemistry In Situ In Situ Hybridization Indium Interdisciplinary Study Laboratories Lead Link Lipids Machine Learning Maintenance Maps Mass Spectrum Analysis Measurement Measures Mechanics Mediator of activation protein Medical Methods Mifepristone Modality Molecular Molecular Profiling Monitor Mus Optics Phenotype Physiological Pregnancy Premature Birth Premature Labor Prevention Process Proline Property Proteins Proteomics RU-486 Raman Spectrum Analysis Reproductive Biology Research Research Methodology Research Personnel Research Project Grants Spectrum Analysis Staging Structure Surface Techniques Technology Testing Time Tissues Translating Translations Tyrosine Woman base clinical application in vivo infant morbidity/mortality innovation insight mouse model novel novel diagnostics novel therapeutic intervention physical science predictive modeling pregnant premature public health relevance response tool

项目摘要

DESCRIPTION (provided by applicant): Our understanding of cervical remodeling during pregnancy and labor is incomplete, partly due to the lack of in vivo studies on the biochemical changes that occur in the cervix over the course of pregnancy. Elucidation of the mechanisms for cervical ripening could be used to predict the onset of preterm labor. Until recently, in vivo research methods were too invasive to be used as discovery tools, particularly in women who present with preterm labor. This proposal will use in vivo Raman spectroscopy, an optical technique that is sensitive to collagen content, collagen structure, hydration, lipids, proteins, ad other biomolecules to non-invasively investigate the biochemistry of the cervix throughout pregnancy. Using fiber optic in vivo Raman spectroscopy, we recently found significant differences in Raman spectra in at least four important peaks during the course of pregnancy in mice, including discrete signatures for lipids, collagen, amide bonds, and enriched amino acids (proline, tyrosine). Computational analysis of these spectra yielded predictive algorithms with 94% classification accuracy for stage of pregnancy. Studies performed in 2-hour windows at the end of pregnancy identified spectra predictive for the timing of parturition. This approach provides a detailed real-time biomolecular map of cervical ripening that is currently unavailable by other means. In this proposal, we hypothesize that the different mechanisms of premature cervical ripening have unique Raman spectral signatures that correspond to underlying biochemical and mechanical changes that precede preterm birth, which can be detected in vivo. Two Specific Aims are proposed: 1) Determine spectral changes in the cervix of mice with normal and abnormal pregnancy and parturition; 2) Identify specific mediators of cervical remodeling by comparing Raman spectra to mechanical and biochemical changes in the ex vivo cervix during normal and abnormal parturition. Raman spectroscopy has primarily been used for detection of disease. Collaboration between our reproductive biology and bioengineering groups will capitalize on our expertise in Raman analysis of cervical tissues to study dynamic changes in cervix composition during pregnancy. Key elements in cervical biochemistry will be identified. In vivo Raman spectroscopy will be combined with biomechanical studies and imaging mass spectrometry, a powerful tool for in situ proteomic analysis, to examine mice with premature or delayed cervical remodeling. Together, these highly innovative approaches will generate in-depth profiles of cervical biology that will translate into novel non-invasive methods to detect impending premature birth in women.

描述（由申请人提供）：我们对妊娠和分娩期间宫颈重塑的理解并不完整，部分原因是缺乏对妊娠过程中宫颈发生的生化变化的体内研究。阐明宫颈成熟机制可用于预测早产的发生。直到最近，体内研究方法的侵入性太大，无法用作发现工具，特别是对于出现早产的女性。该提案将使用体内拉曼光谱，这是一种对胶原蛋白含量、胶原蛋白结构、水合作用、脂质、蛋白质和其他生物分子敏感的光学技术，以非侵入性方式研究整个怀孕期间子宫颈的生物化学。使用光纤体内拉曼光谱，我们最近发现小鼠怀孕期间至少四个重要峰的拉曼光谱存在显着差异，包括脂质、胶原蛋白、酰胺键和富集氨基酸（脯氨酸、酪氨酸）的离散特征。对这些光谱的计算分析得出了妊娠阶段分类准确度为 94% 的预测算法。在妊娠结束时的 2 小时窗口内进行的研究确定了可预测分娩时间的光谱。这种方法提供了宫颈成熟的详细实时生物分子图谱，这是目前其他方法无法获得的。在这项提议中，我们假设宫颈早熟的不同机制具有独特的拉曼光谱特征，这些特征对应于早产之前潜在的生化和机械变化，这些变化可以在体内检测到。提出了两个具体目标：1）确定正常和异常妊娠和分娩小鼠子宫颈的光谱变化； 2) 通过将拉曼光谱与正常和异常分娩期间离体宫颈的机械和生化变化进行比较，识别宫颈重塑的特定介质。拉曼光谱主要用于疾病检测。我们的生殖生物学和生物工程团队之间的合作将利用我们在宫颈组织拉曼分析方面的专业知识来研究怀孕期间宫颈成分的动态变化。将确定宫颈生物化学的关键要素。体内拉曼光谱将与生物力学研究和成像质谱（原位蛋白质组分析的强大工具）相结合，以检查过早或延迟宫颈重塑的小鼠。这些高度创新的方法将共同产生宫颈生物学的深入概况，并将其转化为新型非侵入性方法来检测女性即将发生的早产。