All human lives start with pregnancy. A pathological pregnancy can be physically, mentally, and financially detrimental to newborns and families. Preterm labor and birth (PTB) is one of the most serious pathological conditions associated with pregnancy. PTB affects 10% of global births and is the leading cause of death in children under five years of age. Multiple etiologies are identified for causing PTB and three major reproductive tissues are involved: the uterus, the cervix, and the feto–maternal interface. Throughout pregnancy, these reproductive tissues change in response to various signals, a process called remodeling. Timely and appropriate remodeling of these tissues is needed for a healthy pregnancy. One central element of remodeling is a change in tissues’ mechanical properties, the focus of this work.
This dissertation investigates the mechanical environment of pregnancy by characterizing the remodeling of three reproductive tissues of primates (humans and Rhesus macaque monkeys) and computationally simulating pregnancy physiology. I combine comprehensive mechanical testing with digital image correlation (DIC) to capture the material behavior of reproductive tissues, characterize the architecture of these tissues’ fiber networks by optical coherence tomography (OCT), implement a microstructurally-inspired constitutive mate- rial model, conduct inverse finite element analysis (IFEA) to quantify observed remodeling, and finally use finite element analysis (FEA) to simulate pregnancy anatomy and physiology.
Results presented here demonstrate that the non-human primate (NHP) cervix, human uterus, and NHP feto–maternal interface all undergo remodeling during pregnancy and experience com- plex stress conditions. In general, the NHP cervix becomes softer and more extensible, with distinct stages. While the ground substance compressibility stays approximately the same throughout gestation, the fiber network steadily becomes more extensible, though rapidly becomes less stiff and more dispersed during the second trimester.
The human uterus late in gestation is softer and more extensible compared to its NP state; most of its remodeling involves changes to fiber network extensibility and architecture. The NHP feto–maternal interface adhesion strength reaches a peak early in the third trimester. Lastly, I generated preliminary subject-specific finite element models of NHP by using a workflow developed for human data. By doing this, the complex stress and stretch conditions that reproductive tissues undergo during pregnancy can be visualized. Future work advancing our understanding of pregnancy and women’s health should include the characterization of the time-dependent properties of reproductive tissues, investigation of the relationship between quantitative ultrasound measurements and tissues’ mechanical properties, and improvements to the current FEA workflow.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/dbs1-as34 |
| Date | January 2023 |
| Creators | Fang, Shuyang |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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