Birth, Muscle Injury and Pelvic Floor Dysfunction

描述(申请人提供)：尽管几千年来人们都知道，许多通过阴道分娩的年轻女性在晚年会患上致残性盆腔器官脱垂，但将这两个事件联系在一起的因素仍然是一个谜。在每年通过阴道分娩的300万妇女中，有30万人，即十分之一的妇女，由于她们在生殖中独特的性别决定作用，稍后将需要手术治疗盆底功能障碍。我们发现由出生引起的提肛肌损伤及其与脱垂的密切关系已经确定了出生和脱垂之间的关键联系。对产伤是如何发生的，以及它是如何产生随后的脱垂的无知，阻碍了改进预防和治疗的努力。在这份申请中，我们寻求继续为我们代表4所学校和2个研究所的跨学科性别差异研究小组提供SCOR支持。在过去的四年里，该组织因我们的发现而获得了10个奖项，现在正在寻求资金，开始将这些见解转化为改善出生时的预防和更好的治疗策略。项目I“分娩生物力学”将测试有关阴道分娩期间提肛肌损伤的基本机制的假说，以确定可能增加或降低损伤风险的特定情况。项目二“损伤范围”将确定初产后临床上轻微的提肌损伤是否扩展到 二胎时有明显的临床撕裂。因为第二次生育会使生殖器脱垂的风险增加一倍，这一事件提供了在以后的生活中预防伤害及其后遗症的机会。项目III“肌肉-韧带动力学”将确定与出生相关的提肌损伤和与脱垂相关的子宫阴道支持韧带的特性之间的相互作用。核心A“行政/人类科目”整合和支持跨学科团队，并通过招募科目、汇编和分析数据以及保护科目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，并对项目收集的2维和3维空间数据进行综合分析。它将准备数据，以供演示、发布、主题安全分析，并最终公开使用。核心C“翻译/指导”与\促进洞察力传播和推动调查员发展。这一SCOR将产生翻译洞察力，以减少女性因其在生殖中的独特作用而遭受的性别决定后果。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.