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

这个学院早期职业发展计划(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，产生强烈的收缩，以便分娩，但却恢复到原来的形状，为下一次怀孕做准备。如果子宫过早收缩，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--这使得预测分娩的时间变得困难。该项目将开发一个计算机模型，以确定怀孕期间由于胎儿生长控制、子宫适应和机械功能而发生的变化。这项研究将通过提供对怀孕期间子宫变化的更好的了解来促进孕妇和婴儿的健康。从这个项目中获得的知识对其他器官也有影响，在这些器官中，即使是子宫中观察到的量的一小部分变形也可能导致机械故障。此外，该项目将支持一项教育计划，以促进怀孕和为人父母的高中女孩参与科学和工程。这项研究将被纳入一个针对怀孕和为人父母的高中女孩的实践教育模块，她们将在校园内体验大学生活。这个项目的研究目标是揭示在怀孕期间驱动子宫生长、重塑和机械功能的机械信号。基于已知的子宫机械适应能力，研究目标包括1)对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所经历的机械信号？B)控制子宫平滑肌细胞生长的机械信号是什么？C)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力学生物学的知识。这项研究被纳入以怀孕和育儿女孩为目标的外联活动，这些女孩在科学和工程领域的代表性严重不足。总而言之，该项目支持首席研究员通过研究改善女性生活的长期愿景，并使在女性健康研究领域寻求职业生涯的工程劳动力多样化。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.