Mechanisms and Impact of Pregnancy-Induced Adaptations in Pelvic Floor Muscles

怀孕引起的盆底肌肉适应的机制和影响

基本信息

批准号：
10689277
负责人：
Marianna Alperin
金额：
$ 62.87万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10689277
关键词：
Acute Adult Anatomy Animal Model Animals Architecture Area Biological Assay Biological Process Birth Birth trauma Cell Transplantation Cells Cesarean section Childbirth Clinical Research Cues Data Development Disparity Economic Burden Endocrine Environment Estrogens Exhibits Experimental Models Exposure to Female Functional disorder Future Genetic Transcription Growth High Prevalence Hormonal Human In Situ In Vitro Inbreeding Injury Investigation Knowledge Limb structure Link Longevity Maps Mechanics Modeling Modification Molecular Morbidity - disease rate Morphology Muscle Muscle satellite cell Natural regeneration Oxytocin Partner in relationship Pelvic Floor Disorders Pelvic Floor Muscle Pelvic floor dysfunction Pelvic floor structure Pelvis Perinatal Phenotype Physiological Population Postpartum Period Pre-Clinical Model Pregnancy Preparation Prevention strategy Preventive therapy Process Progesterone Proliferating Property Protocols documentation Public Health Rattus Recovery Regenerative capacity Regulation Relaxin Research Risk Factors Role Sarcomeres Serum Signal Pathway Signal Transduction Signaling Molecule Skeletal Muscle Skeletal Muscle Satellite Cells Source Testing Therapeutic Time Trauma United States National Institutes of Health Vagina Vaginal delivery procedure Vision Woman Women&apos s Health antenatal candidate identification clinical care epigenomics experimental study improved in vivo injury recovery innovation insight interdisciplinary approach intrapartum knowledge of results male minimally invasive modifiable risk multiple omics muscle regeneration novel novel strategies postmitotic pre-clinical pregnant prevent regeneration potential repaired response satellite cell skeletal muscle growth skeletal muscle plasticity soft tissue stem validation studies

项目摘要

PROJECT SUMMARY Our proposal exemplifies the NIH vision that the multidisciplinary approach to clinical care and research is the most fruitful paradigm for the development of significant advancements within a specific field. While it is unfortunate that the heavy focus of skeletal muscle research on the appendicular muscles in male animal models led to scarcity of preclinical investigations in the area of female pelvic skeletal muscles and provided little progress toward preventative or therapeutic approaches that target female-specific conditions, such as pelvic floor disorders; the current project builds on the discoveries of the landmark studies conducted in the limb muscles. Here, we focus on building the foundational knowledge pertaining to female pelvic floor muscle -specific muscle stem cells and the impact of such critical time-periods as pregnancy and childbirth on these cells. The above is necessary for future development of pragmatic preventative approaches to reduce the impact of morbid pelvic floor disorders on public health. This project represents a novel approach focused on elucidating the role of muscle stem cells in pregnancy-induced antepartum adaptations of the pelvic floor muscles as well as muscle regenerative potential following vaginal delivery. To achieve this objective, we will use our validated experimental model to examine the phenotypic, functional, transcriptional, and epigenomic signatures of pelvic muscle stem cells at multiple time points across gestation, parturition, and postpartum period to identify candidate signaling pathways regulating their functional state. We will then test whether exposure to different aspects of the ante- and peripartum environment modulates the regenerative potential of pelvic muscle stem cells and impacts muscle recovery following injury. Overall, this innovative study will provide fundamental insights into the biological processes involved in the regulation of female pelvic muscle satellite cells and factors that impact their regenerative capacity following mechanical injury. The resulting knowledge will enable the development of novel strategies to prevent or treat female pelvic muscle dysfunction.

项目概要我们的提案体现了 NIH 的愿景，即临床护理和研究的多学科方法是在特定领域内取得重大进步的最富有成效的范例。虽然它是不幸的是，骨骼肌研究的重点是雄性动物模型的四肢肌导致女性盆腔骨骼肌领域的临床前研究匮乏，并且提供的信息很少针对女性特定病症（例如盆腔）的预防或治疗方法取得进展地板障碍；当前的项目建立在肢体里程碑式研究的发现之上肌肉。在这里，我们专注于建立与女性盆底肌肉特定相关的基础知识肌肉干细胞以及怀孕和分娩等关键时期对这些细胞的影响。这以上对于未来制定务实的预防方法以减少病态影响是必要的盆底疾病对公共卫生的影响。该项目代表了一种专注于阐明角色的新颖方法肌肉干细胞在妊娠引起的盆底肌肉和肌肉产前适应中的作用阴道分娩后的再生潜力。为了实现这一目标，我们将使用经过验证的实验用于检查盆腔肌干的表型、功能、转录和表观基因组特征的模型妊娠、分娩和产后期多个时间点的细胞，以确定候选信号传导调节其功能状态的途径。然后我们将测试是否暴露于不同方面的前围产期环境调节盆腔肌肉干细胞的再生潜力并产生影响受伤后的肌肉恢复。总体而言，这项创新研究将为以下方面提供基本见解：参与调节女性盆腔肌卫星细胞的生物过程以及影响其的因素机械损伤后的再生能力。由此产生的知识将有助于开发新颖的预防或治疗女性盆腔肌肉功能障碍的策略。