Biaxial biomechanical properties of the nonpregnant murine cervix and uterus.

From a biomechanical perspective, female reproductive health is an understudied area of research. There is an incomplete understanding of the complex function and interaction between the cervix and uterus. This, in part, is due to the limited research into multiaxial biomechanical functions and geometry of these organs. Knowledge of the biomechanical function and interaction between these organs may elucidate etiologies of conditions such as preterm birth. Therefore, the objective of this study was to quantify the multiaxial biomechanical properties of the murine cervix and uterus using a biaxial testing set-up. To accomplish this, an inflation-extension testing protocol (n = 15) was leveraged to quantify biaxial biomechanical properties while preserving native matrix interactions and geometry. Ultrasound imaging and histology (n = 10) were performed to evaluate regional geometry and microstructure, respectively. Histological analysis identified a statistically significant greater collagen content and significantly smaller smooth muscle content in the cervix as compared to the uterus. No statistically significant differences in elastic fibers were identified. Analysis of bilinear fits revealed a significantly stiffer response from the circumferentially orientated ECM fibers compared to axially orientated fibers in both organs. Bilinear fits and a two-fiber family constitutive model showed that the cervix was significantly less distensible than the uterus. We submit that the regional biaxial information reported in this study aids in establishing an appropriate reference configuration for mathematical models of the uterine-cervical complex. Thus, may aid future work to elucidate the biomechanical mechanisms leading to cervical or uterine conditions.

Toward Automation of the Supine Pressor Test for Preeclampsia.

Preeclampsia leads to increased risk of morbidity and mortality for both mother and fetus. Most previous studies have largely neglected mechanical compression of the left renal vein by the gravid uterus as a potential mechanism. In this study, we first used a murine model to investigate the pathophysiology of left renal vein constriction. The results indicate that prolonged renal vein stenosis after 14 days can cause renal necrosis and an increase in blood pressure (BP) of roughly 30 mmHg. The second part of this study aimed to automate a diagnostic tool, known as the supine pressor test (SPT), to enable pregnant women to assess their preeclampsia development risk. A positive SPT has been previously defined as an increase of at least 20 mmHg in diastolic BP when switching between left lateral recumbent and supine positions. The results from this study established a baseline BP increase between the two body positions in nonpregnant women and demonstrated the feasibility of an autonomous SPT in pregnant women. Our results demonstrate that there is a baseline increase in BP of roughly 10-14 mmHg and that pregnant women can autonomously perform the SPT. Overall, this work in both rodents and humans suggests that (1) stenosis of the left renal vein in mice leads to elevation in BP and acute renal failure, (2) nonpregnant women experience a baseline increase in BP when they shift from left lateral recumbent to supine position, and (3) the SPT can be automated and used autonomously.

Angiotensin II Infusion Does Not Cause Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Rats.

The apolipoprotein E-deficient (apoE-/-) mouse model has advanced our understanding of cardiovascular disease mechanisms and experimental therapeutics. This spontaneous model recapitulates aspects of human atherosclerosis, and allows for the development of dissecting abdominal aortic aneurysms (AAAs) when combined with angiotensin II. We characterized apoE-/- rats and hypothesized that, similar to mice, they would develop dissecting AAAs. We created rats with a 16-bp deletion of the apoE gene using transcription activator-like effector nucleases. We imaged the suprarenal aorta for 28 days after implantation of miniosmotic pumps that infuse angiotensin II (AngII, 200 ng/kg/min). Blood pressure (BP), serum lipids and lipoproteins, and histology were also analyzed. These rats did not develop pathological aortic dissection, but we did observe a decrease in circumferential cyclic strain, a rise in BP, and microstructural changes in the aortic medial layer. We also measured increased serum lipids with and without administration of a high-fat diet, but did not detect atherosclerotic plaques. Chronic infusion of AngII did not lead to the formation of dissecting AAAs or atherosclerosis in the rats used in this study. While reduced amounts of atherosclerosis may explain this resistance to dissecting aneurysms, further investigation is needed to fully characterize species-specific differences.