CAREER: Growth and Remodeling of the Uterine Cervix During Pregnancy

职业：怀孕期间子宫颈的生长和重塑

• 批准号: 1454412
• 负责人: Kristin Myers
• 金额: $ 50万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1454412&HistoricalAwards=false
• 关键词: CAREER; Growth; Remodeling; Uterine; Cervix

This NSF Faculty Early Career Development (CAREER) Program award will characterize the biomechanical mechanisms that cause preterm birth (PTB) and will train the next generation of female engineers with educational activities geared towards Women's Health. Despite advances in prenatal care, the rate of PTB (birth before 37 weeks of gestation) in the United States remains high. This fact underscores how little is known about the causes of PTB, which is a leading cause of death in children under five. Researchers do know that the cervix, a cylindrical organ located at the base of the uterus, is a critical mechanical barrier to maintain the baby to full term. Then, at time of delivery the cervix is instructed by hormonal cues to remodel, soften, and dilate to become a safe passage for the baby. If this cervical tissue remodeling timing is off, PTB can occur due to premature cervical dilation. The understanding of this cervical remodeling process is limited because there are no engineering tools to characterize normal and abnormal cervical softening. To address this need, this study will measure the mechanical and biochemical property changes of the cervix under various hormonal cues and derive a set of equations that can predict the mechanical function of the cervix during pregnancy. This study will bring an improved understanding to the underlying causes of PTB related to cervical dysfunction, and will be an essential step toward the development of rational therapies to prevent PTB.This CAREER study will derive a constitutive material modeling framework for the growth and remodeling of the cervix during pregnancy. The main goal is to determine the driving factors that cause premature cervical remodeling and the mechanical dysfunction of the cervix. The modeling framework will be based on the evidence that levels of estrogen and progesterone play a key role in regulating cervical tissue composition during pregnancy. Cervical tissue will be modeled as a hydrated fiber composite porous material where the interstitial pore space allows for the growth and removal of solid mass. The associated material parameters will evolve as a function of hormone-mediated extracelluar matrix compositional state variables. Model functions will be based on mechanical and collagen characterization of gestation-timed cervical tissue samples taken from established mouse models of hormone-mediated normal, preterm, and disrupted cervical remodeling. These equations will be validated by assessing their predictive capability of the material response to loading and hormonally-driven tissue changes.

这个NSF教师早期职业发展（CAREER）计划奖将描述导致早产（PTB）的生物力学机制，并将通过面向女性健康的教育活动培训下一代女工程师。尽管产前护理取得了进展，但美国的PTB（妊娠37周前出生）率仍然很高。这一事实凸显了人们对肺结核的病因知之甚少，而肺结核是五岁以下儿童死亡的主要原因。研究人员确实知道，子宫颈，一个位于子宫底部的圆柱形器官，是维持婴儿足月的关键机械屏障。然后，在分娩时，子宫颈会受到荷尔蒙信号的指导，重塑，软化和扩张，成为婴儿的安全通道。如果子宫颈组织重塑时机关闭，PTB可能由于子宫颈过早扩张而发生。对宫颈重塑过程的理解是有限的，因为没有工程工具来表征正常和异常的宫颈软化。为了满足这一需求，本研究将测量子宫颈在各种激素提示下的机械和生化特性变化，并推导出一组方程，可以预测怀孕期间子宫颈的机械功能。这项研究将带来一个更好的了解子宫颈功能障碍相关的PTB的根本原因，并将朝着合理的治疗，以防止PTB的发展是一个重要的一步。这项CAREER研究将得出一个构成材料建模框架的生长和重塑的子宫颈在怀孕期间。主要目标是确定导致宫颈过早重塑和宫颈机械功能障碍的驱动因素。模型框架将基于雌激素和孕激素水平在妊娠期间调节宫颈组织成分中起关键作用的证据。宫颈组织将被建模为水合纤维复合多孔材料，其中间隙孔隙允许固体物质的生长和去除。相关的材料参数将演变为一个功能的介导的细胞外基质组成的状态变量。模型功能将基于妊娠时宫颈组织样本的机械和胶原表征，这些样本取自已建立的子宫内膜介导的正常、早产和宫颈重塑中断的小鼠模型。将通过评估材料对载荷和骨驱动组织变化的响应的预测能力来验证这些方程。