CAREER: Biomechanics and Mechanobiology of Uterine Growth and Remodeling During Pregnancy

职业：妊娠期间子宫生长和重塑的生物力学和力学生物学

• 批准号: 2236961
• 负责人: Kyoko Yoshida
• 金额: $ 57.81万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2236961&HistoricalAwards=false
• 关键词: CAREER; Biomechanics; Mechanobiology; Uterine; Growth

This Faculty Early Career Development Program (CAREER) project will investigate how mechanical loading controls changes in the uterus during pregnancy. During pregnancy, the uterus remains relaxed while growing and stretching to accommodate the developing fetus. Conversely, the uterus activates at term to produce forceful contractions for delivery, only to return to its original shape to prepare for the next pregnancy. If the uterus contracts too early, the pregnancy can result in preterm birth, which is a leading cause of death in children under five. The understanding of how the uterus remains relaxed, activates, and reverses its adaptations to pregnancy is limited - making it difficult to predict the timing of labor. This project will develop a computer model to identify how changes due to the growing fetus control uterine adaptations and mechanical function during pregnancy. This research will advance the health of pregnant patients and babies by providing an improved understanding of uterine changes during pregnancy. The knowledge gained from this project also has implications for other organs, where deformations of even a fraction of the amount observed in the uterus can lead to mechanical failure. Further, this project will support an educational program to foster engagement of pregnant and parenting high school girls in science and engineering. The research will be incorporated into a hands-on educational module for pregnant and parenting high school girls, who will be hosted for an on-campus college experience. The research goal of this project is to uncover the mechanical signals that drive uterine growth, remodeling, and mechanical function during pregnancy. Based on the known mechanoadaptive capabilities of the uterus, the research objectives include 1) experimental quantification of uterine growth and remodeling biomechanics during a normal mouse pregnancy, and 2) building, validating, and testing a growth and remodeling finite element model of uterine mechanobiology. Critical questions to be answered include: A) How do uterine loading, growth, and remodeling interact and influence the mechanical cues that uterine smooth muscle cells experience? B) What mechanical cues control uterine smooth muscle cell growth? and C) Do the mechanobiological mechanisms of normal uterine adaptations apply to abnormal pregnancies? Through these experimental and computational studies, this research will advance the knowledge of uterine biomechanics and mechanobiology. The research is integrated into outreach activities that target pregnant and parenting girls, who are severely underrepresented in science and engineering. Together, this project supports the principal investigator's long-term vision to improve the lives of women through research and to diversify the engineering workforce pursuing careers in women's health research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个教师早期职业发展计划（CAREER）项目将调查机械负荷如何控制怀孕期间子宫的变化。在怀孕期间，子宫保持放松，同时生长和伸展以适应发育中的胎儿。相反，子宫在足月时激活，产生分娩时的有力收缩，只是为了恢复其原始形状，为下一次怀孕做准备。如果子宫收缩过早，怀孕可能导致早产，这是五岁以下儿童死亡的主要原因。对子宫如何保持放松，激活和逆转其对怀孕的适应的理解是有限的-这使得难以预测分娩的时间。该项目将开发一个计算机模型，以确定如何变化，由于不断增长的胎儿控制子宫适应和机械功能在怀孕期间。这项研究将通过提供对怀孕期间子宫变化的更好理解来促进怀孕患者和婴儿的健康。从这个项目中获得的知识也对其他器官有影响，即使是子宫中观察到的一小部分变形也会导致机械故障。此外，该项目将支持一项教育计划，以促进怀孕和养育高中女生参与科学和工程。这项研究将被纳入一个实践教育模块，为怀孕和养育高中女生，谁将被主办的校园内的大学经验。该项目的研究目标是揭示妊娠期间驱动子宫生长，重塑和机械功能的机械信号。基于子宫已知的机械适应能力，研究目标包括1）正常小鼠妊娠期间子宫生长和重塑生物力学的实验量化，以及2）建立，验证和测试子宫机械生物学的生长和重塑有限元模型。需要回答的关键问题包括：A）子宫负荷，生长和重塑如何相互作用并影响子宫平滑肌细胞经历的机械信号？B）什么样的机械信号控制子宫平滑肌细胞的生长？正常子宫适应的机械生物学机制是否适用于异常妊娠？通过这些实验和计算研究，本研究将推进子宫生物力学和机械生物学的知识。这项研究被纳入针对怀孕和育儿女孩的外联活动，这些女孩在科学和工程领域的代表性严重不足。该项目支持首席研究员的长期愿景，即通过研究改善妇女的生活，并使从事妇女健康研究的工程人员多样化。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。