Birth, Muscle Injury and Pelvic Floor Dysfunction

描述（由申请人提供）：尽管几千年来人们都知道，许多阴道分娩的年轻女性在其生命后期会遭受致残性盆腔器官脱垂，但将这两种事件联系起来的因素仍然是一个谜。在每年300万阴道分娩的妇女中，有30万或十分之一的妇女由于其在生殖中独特的性别决定作用而需要进行骨盆底功能障碍手术。我们发现了分娩引起的肛提肌损伤及其与脱垂的密切关系，确定了分娩和脱垂之间的关键联系。对产伤如何发生及其如何导致随后的脱垂的无知阻碍了改善预防和治疗的努力。在这个应用程序中，我们寻求继续SCOR支持我们广泛的跨学科的性别差异研究小组代表4所学校和2所研究所。在过去的4年里，该小组因我们的发现赢得了10个奖项，现在正在寻求资金，以开始将这些见解转化为改进的出生时预防和更好的治疗策略。项目I“分娩生物力学”将测试关于阴道分娩期间肛提肌损伤的基本机制的假设，以确定可能增加或减少损伤风险的特定情况。项目II“损伤扩展”将确定第一胎后临床上无意义的轻微提肌损伤是否扩展到 在第二次分娩时出现临床上显著的撕裂。由于第二胎生殖器脱垂的风险增加一倍，这一事件提供了预防损伤及其后遗症的机会。项目III“肌肉-韧带动力学”将建立与生产相关的提上睑肌损伤和与脱垂相关的子宫阴道支撑韧带的性质之间的相互作用。Core A“行政/人类受试者”整合并支持跨学科团队，通过招募受试者、编辑和分析数据以及保护受试者安全来提供项目支持。核心B“生物统计/测量”为项目提供统计和技术支持，沿着对项目间收集的二维和三维空间数据进行综合分析。它将准备数据用于演示，出版，受试者安全分析和最终公众使用。 核心C“翻译/导师制“将促进洞察力的传播并推动研究者的发展。该SCOR将产生翻译见解，以减少女性因其在生殖中的独特作用而遭受的性别决定的后果。它将为改善治疗的新战略奠定科学基础，确定重要的预防机会，并培训新一代研究人员。

DESCRIPTION (provided by applicant): Although it has been known for millennia that many young women who give birth vaginally will suffer from disabling pelvic organ prolapse later in their lifespan, the factors linking these two events remain a mystery. Of the 3 million women who deliver vaginally each year 300,000 or 1 in 10 will later require surgery for pelvic floor dysfunction due to their unique sex-determined role in reproduction. Our discovery of birth-induced levator ani muscle injury and its strong relationship to prolapse has identified a key connection between birth and prolapse. Ignorance of how birth-induced injury occurs and how it produces subsequent prolapse has blocked efforts to improve prevention and treatment. In this application we seek to continue SCOR support for our broadly interdisciplinary sex-differences research group representing 4 schools and 2 institutes. The group has won 10 awards in the last 4 years for our discoveries and now seeks funding to begin to translate these insights into improved prevention at birth and strategies for better treatment. Project I "Birth Biomechanics" will test hypotheses concerning basic mechanisms of levator ani injury during vaginal birth to identify specific situations that may increase or decrease injury risk. Project II "Injury Extensio" will determine whether minor clinically insignificant levator injury after first birth extends to a clinically significant tear during second birth. Because a second birth doubles the risk of genital prolapse, this event offers the opportunity of preventing injury and their sequelae later in life. Project III "Muscle-Ligament Dynamics" will establish the interaction between birth-related levator muscle injury and the properties of the uterovaginal supporting ligaments associated with prolapse. Core A "Administrative/Human Subjects" integrates and supports the interdisciplinary team and provides project support by recruiting subjects, compiling and analyzing data and protecting subject safety. Core B "Biostatistics/Measurements" provides statistical and technical support for the projects along with integrated analysis for 2- and 3-dimensional spatial data gathered across projects. It will prepare data for presentation, publication, subject safety analysis and eventually public use. Core C "Translation/Mentorship"w\\\ foster insight dissemination and drive investigator development. This SCOR will produce translational insights to reduce the sex-determined consequences women suffer from their unique role in reproduction. It will establish the scientific basis for new strategies to improve treatment, identify important prevention opportunities, and train a new generation of researchers.