Department of Mechanical Engineering, Columbia University, New York, NY 10027.
Department of Obstetrics and Gynecology, Cecil H. and Ida Green Center for Reproductive Biological Science, The University of Texas, Southwestern Medical Center, Dallas, TX 75390.
J Biomech Eng. 2022 Jun 1;144(6). doi: 10.1115/1.4054199.
Cervical remodeling is critical for a healthy pregnancy. The proper regulation of extracellular matrix (ECM) turnover leads to remodeling throughout gestation, transforming the tissue from a stiff material to a compliant, extensible, viscoelastic tissue prepared for delivery. Small leucine-rich proteoglycans (SLRPs) regulate structural fiber assembly in the cervical ECM and overall tissue material properties. To quantify the SLRPs' mechanical role in the cervix, whole cervix specimens from nonpregnant and late pregnant knockout mice of SLRPs, decorin and biglycan, were subjected to cyclic load-unload, ramp-hold, and load-to-failure mechanical tests. Further, a fiber composite material model, accounting for collagen fiber bundle waviness, was developed to describe the cervix's three-dimensional large deformation equilibrium behavior. In nonpregnant tissue, SLRP knockout cervices have the same equilibrium material properties as wild-type tissue. In contrast, the load-to-failure and ramp-hold tests reveal SLRPs impact rupture and time-dependent relaxation behavior. Loss of decorin in nonpregnant (NP) cervices results in inferior rupture properties. After extensive remodeling, cervical strength is similar between all genotypes, but the SLRP-deficient tissue has a diminished ability to dissipate stress during a ramp-hold. In mice with a combined loss of decorin and biglycan, the pregnant cervix loses its extensibility, compliance, and viscoelasticity. These results suggest that decorin and biglycan are necessary for crucial extensibility and viscoelastic material properties of a healthy, remodeled pregnant cervix.
宫颈重塑对于健康妊娠至关重要。细胞外基质(ECM)的适当调节导致整个妊娠期间的重塑,使组织从坚硬的物质转变为柔韧、可伸展、粘弹性的组织,为分娩做好准备。小富含亮氨酸的蛋白聚糖(SLRPs)调节宫颈 ECM 中的结构纤维组装和整体组织材料特性。为了定量研究 SLRPs 在宫颈中的力学作用,对非妊娠和妊娠晚期 SLRPs、核心蛋白聚糖和 biglycan 缺失的敲除小鼠的整个宫颈标本进行了循环加载-卸载、斜坡保持和负载-失效力学测试。此外,还开发了一种纤维复合材料模型,该模型考虑了胶原纤维束的波浪度,以描述宫颈的三维大变形平衡行为。在非妊娠组织中,SLRP 缺失的宫颈与野生型组织具有相同的平衡材料特性。相比之下,负载-失效和斜坡保持测试揭示了 SLRPs 对破裂和时变松弛行为的影响。非妊娠(NP)宫颈中核心蛋白聚糖的缺失导致破裂性能下降。在广泛重塑后,所有基因型的宫颈强度相似,但 SLRP 缺失的组织在斜坡保持期间的应力消散能力降低。在缺失核心蛋白聚糖和 biglycan 的小鼠中,妊娠宫颈失去了伸展性、顺应性和粘弹性。这些结果表明,核心蛋白聚糖和 biglycan 是健康重塑妊娠宫颈至关重要的伸展性和粘弹性材料特性所必需的。