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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：
10523029
负责人：
Marianna Alperin
金额：
$ 64.32万
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/10523029
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 Economic Burden Endocrine Environment Estrogens Exhibits Experimental Models Exposure to Female Foundations Functional disorder Future Genetic Transcription Growth High Prevalence Hormonal Human In Situ In Vitro Inbreeding Injury Investigation Knowledge Limb structure Link Longevity Maps Mechanics Mitotic 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 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 pre-clinical pregnant prevent regeneration potential repaired response satellite cell skeletal muscle growth skeletal muscle plasticity soft tissue stem

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.

项目总结