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

• 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
• 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

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）：我们对妊娠和人工期间宫颈重塑的理解是不完整的，部分原因是缺乏体内研究对宫颈妊娠过程中子宫颈发生的生化变化的研究。阐明宫颈成熟机制可以用于预测早产的开始。直到最近，体内研究方法的侵入性过于侵入性，无法用作发现工具，尤其是在有早产劳动的女性中。该建议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，脂质，蛋白质，AD其他生物分子敏感的光学技术。使用纤维在体内拉曼光谱学中，我们最近发现，在小鼠怀孕期间，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，酰胺键和富集的氨基酸（脯氨酸，酪氨酸）的离散特征。这些光谱的计算分析得出了预测算法，妊娠期的分类精度为94％。怀孕结束时在2小时窗户上进行的研究确定了针对分娩时间的光谱。这种方法提供了详细的实时生物分子图的宫颈成熟图，目前无法通过其他方式获得。在此提案中，我们假设过早的宫颈成熟的不同机制具有独特的拉曼光谱特征，与早产之前的生化和机械变化相对应，可以在体内检测到。提出了两个具体目的：1）确定妊娠正常和异常妊娠和分娩的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体内子宫颈的机械和生化变化进行比较，确定颈椎重塑的特定介体。拉曼光谱学主要用于检测疾病。我们的生殖生物学与生物工程组之间的合作将利用我们在宫颈组织的拉曼分析方面的专业知识，以研究怀孕期间子宫颈组成的动态变化。将确定宫颈生物化学的关键要素。体内拉曼光谱法将与生物力学研究和成像质谱法相结合，这是一种原位蛋白质组学分析的强大工具，用于检查具有过早或延迟的宫颈重塑的小鼠。总之，这些高度创新的方法将产生宫颈生物学的深入曲线，这些宫颈生物学将转化为新型的非侵入性方法，以检测女性即将来临的早产。