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，许多顺产的年轻女性在以后的生活中会遭受骨盆器官脱垂的痛苦，但联系这两种事件的因素仍然是一个谜。在每年阴道分娩的300万女性中，有30万或十分之一的女性由于其在生殖中独特的性别决定作用而需要手术治疗盆底功能障碍。我们发现，出生引起的提肛肌损伤及其与脱垂的密切关系，确定了出生和脱垂之间的关键联系。对分娩损伤如何发生以及如何导致脱垂的无知阻碍了改善预防和治疗的努力。在这个申请中，我们寻求继续SCOR支持我们广泛跨学科的性别差异研究小组代表4所学校和2个研究所。该小组在过去4年里因我们的发现赢得了10个奖项，现在正在寻求资金，开始将这些见解转化为更好的出生预防和更好的治疗策略。项目一“分娩生物力学”将测试关于阴道分娩时提肛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具体情况。项目II“损伤延伸”将确定初产后临床不显著的轻微提肌损伤是否延伸至a

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.