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In vivo analysis of mammalian fertilization

哺乳动物受精的体内分析

基本信息

批准号：
10311522
负责人：
Irina Larina
金额：
$ 60.48万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-19 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10311522
关键词：
3-Dimensional Animal Model Animals Area Assisted Reproductive Technology Behavior Biological Cells Cilia Clinical Complex Contraceptive methods Contrast Media Data Defect Development Embryo Embryo Transfer Ensure Environment Estradiol Estrous Cycle Event Failure Female Female infertility Fertility Fertilization Fertilization failure Flagella Frequencies Genetic Models Histologic Hormonal Hormones Human Image Imaging Device Individual Infertility Invertebrates Investigation Knockout Mice Laboratories Lead Light Location Longitudinal Studies Male Infertility Mammalian Oviducts Maps Measurement Mediating Methods Modeling Molecular Molecular Genetics Movement Mus Muscle Contraction Oocytes Optical Coherence Tomography Organ Ovulation Pathology Pattern Peer Review Phase Positioning Attribute Pregnancy Procedures Process Progesterone Protocols documentation Publications Publishing Recording of previous events Reproduction Reproductive Biology Reproductive Process Research Research Design Resolution Scanning Sea Urchins Speed Sperm Motility Sperm Tail Superovulation System Time Visualization Zona Pellucida base blastocyst cell motility early pregnancy egg experimental study high resolution imaging hormone regulation human model imaging genetics imaging modality imaging study imaging system in vivo in vivo imaging infertility treatment innovation insight intraperitoneal mouse model optical imaging preimplantation reproductive reproductive tract research study sex sperm cell

项目摘要

PROJECT SUMMARY/ABSTRACT Estrous cycle, ovulation, fertilization, and pre-implantation pregnancy are fundamental reproductive processes of clinical importance. While research has shed light on the cellular and molecular mechanisms mediating these events, much of these data are derived from static histological analysis, low-resolution visualizations, and studies of invertebrate models (e.g. sea urchin). Therefore, any conclusions regarding mammalian fertilization, which takes place deep inside the body, are extrapolated and do not necessarily represent the native state. If this technical limitation was overcome, we may gain a more complete understanding of mammalian reproduction leading to the development of better fertility treatments and Assisted Reproductive Technologies (ART). By integrating expertise in live, functional optical coherence tomography (OCT) and reproductive biology, we recently established a set of unique methods for in vivo imaging of the female mouse reproductive tract. Our approach allows for (i) live, dynamic volumetric imaging of the mouse Fallopian tube (oviduct) with micro- scale spatial resolution, (ii) depth-resolved mapping of oviduct cilia location and cilia beat frequency (CBF); and (iii) tracking of individual sperm and their motility within the oviduct. None of these measurements are currently possible with other methods, and the dynamic environment of the female reproductive tract is too complex to model. Therefore, we are in a unique position to directly visualize specific mammalian reproductive processes from an entirely new vantage point. We propose the first in vivo volumetric imaging study of mammalian fertilization. This study is taking advantage of new technological developments in OCT imaging and will allow for quantitative assessment of hormonal regulation of oviduct cilia beating and muscle contractions, and functional analysis of fertility failures in mouse models of human defects. This study will likely provide new insight on the process of mammalian fertilization in its native state and lead to a better understanding of pathologies resulting in infertility. It will also establish new functional live imaging tools, which will be a major step forward in reproductive research. Scientific Premise, Scientific Rigor, and Relevant Biological Variables: This proposal is aimed to fill a significant gap in the field of reproductive biology through highly innovative live imaging methods, which we developed. All proposed experiments are supported by strong preliminary data, which have been published in four peer-reviewed publications; one more publication is currently under review. We carefully articulated the number of experimental animals to be used, and the rationale for the choice of the models. “Sex as a biological variable” does not apply to our study design. Extensive details and references to our published protocols are provided to ensure that preliminary and proposed experiments can be replicated in other laboratories.

项目总结/摘要发情周期、排卵、受精和着床前妊娠是基本的生殖过程临床重要性。虽然研究揭示了介导细胞和分子机制，这些事件，这些数据中的大部分来自静态组织学分析，低分辨率可视化，和无脊椎动物模型研究（例如海胆）。因此，任何关于哺乳动物的结论受精，发生在身体深处，是外推的，并不一定代表本土国家。如果克服了这一技术限制，我们就可以更全面地了解哺乳动物生殖导致更好的生育治疗和辅助生殖的发展技术（ART）。通过整合活体、功能性光学相干断层扫描（OCT）和生殖生物学方面的专业知识，最近建立了一套独特的方法，用于雌性小鼠生殖道的体内成像。我们的方法允许（i）小鼠输卵管（输卵管）的实时动态体积成像，尺度空间分辨率，（ii）输卵管纤毛位置和纤毛跳动频率（CBF）的深度分辨映射;以及 (iii)跟踪单个精子及其在输卵管内的运动。这些测量值目前都不是可能与其他方法，和女性生殖道的动态环境太复杂，模型因此，我们处于一个独特的位置，直接可视化特定的哺乳动物生殖过程从一个全新Vantage 我们提出了第一个在体内体积成像研究哺乳动物受精。这项研究利用了 OCT成像的新技术发展，并将允许定量评估激素小鼠输卵管纤毛运动和肌肉收缩的调节及生育障碍的功能分析人类缺陷的模型。这项研究可能会为哺乳动物受精过程提供新的见解，它的原生状态，并导致更好地了解导致不孕症的病理。它还将建立新的功能性活体成像工具，这将是生殖研究向前迈出的重要一步。科学假设、科学严谨性和相关生物变量：本提案旨在填补通过高度创新的活体成像方法，我们在生殖生物学领域的重大差距，开发所有提出的实验都得到了强有力的初步数据的支持，这些数据已发表在《科学》杂志上。 4份经同行审查的出版物;还有1份出版物目前正在审查中。我们仔细阐述了使用的实验动物数量，以及模型选择的依据。“性作为一种生物学变量”不适用于我们的研究设计。我们已发布的方案的详细信息和参考资料如下：确保初步和拟议的实验可以在其他实验室复制。