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

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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.