Collagen concentration and biomechanical properties of samples from the lower uterine cervix in relation to age and parity in non-pregnant women

Abstract

BackgroundDuring normal pregnancy the cervix has a load bearing function. The cervical tissue consists mainly of an extracellular matrix (ECM) rich in collagen; important for the biomechanical properties. The aim of the present study was to evaluate how the biomechanical strength of samples from the distal cervix is associated with collagen content in relation to age and parity. This study demonstrates a method to investigate cervical tissue from women who still have their uterus in situ.MethodsCervical punch biopsies (2 × 15 mm) were obtained from 57 healthy women (median age: 39 years, range: 29-49 years). Biomechanical tensile testing was performed, and collagen concentration (as % of dry defatted weight (DDW)) and content (mg of collagen per mm of specimen length) was determined. Histomorphometry was used to determine the volume densities of extracellular matrix and smooth muscle cells. Smooth muscle cells were identified by immunohistochemistry. Finally, orientation of collagen fibers was estimated. Data are given as mean +/- SD.ResultsThe mean collagen concentration (62.2 +/- 6.6%) increased with age (0.5% per year, r = 0.45, p = 0.003) and decreased with parity (1.7% per birth, r = -0.45, p = 0.033). Maximum load was positively correlated with collagen content (mg of collagen per mm of specimen length) (r = 0.76, p < 0.001). Normalized maximum stiffness was increased with age (r = 0.32, p = 0.017), whereas no correlation was found with regard to parity. In tissue samples with a length of approximately one cm, volume density of smooth muscle cells increased gradually from 8.9% in the distal part near the epithelium, to 15.5% in the proximal part (p < 0.001).ConclusionsThe present study shows that cervical collagen concentration increases with age and decreases with parity in non-pregnant women. In addition, collagen stiffness increased with age, whereas no change in collagen tensile strength with respect to age and parity was found. These results show that collagen contributes to cervical tissue tensile strength and age and parity should be considered confounding factors.

The mechanical role of the cervix in pregnancy

“…Age is known to affect the mechanical properties of nonpregnant cervical tissue. Spherical indentation tests reveal that older samples have a lower force response to compressive indentation (Yao et al, 2014), while in another study the uni-axial tensile response to loading for older tissue is higher (Oxlund et al, 2010b). Age is an important factor because most ex vivo studies have been conducted on hysterectomy specimens, and the age of the hysterectomy patient is often older than that of a typical pregnant patient.…”

“…Insight into the physiologic loads experienced during pregnancy and the load-carrying capability of the cervix have been derived from finite element models (Fernandez et al, 2015; House et al, 2012, 2013; Mahmoud et al, 2013; Paskaleva, 2007), mechanical and biochemical studies of ex vivo tissue specimens (Conrad et al, 1980; Conrad and Ueland, 1976, 1979; Fernandez et al, 2013; Gan et al, 2014; Myers et al, 2008, 2010; Oxlund et al, 2010a,b; Petersen et al, 1991; Rechberger et al, 1988; Yao et al, 2014), in vivo mechanical and biochemical interrogations of the cervix (Badir et al, 2013a; Bauer et al, 2007; Feltovich et al, 2010, 2012; Feltovich and Hall, 2013; Hee et al, 2014; House et al, 2005, 2009; Hricak et al, 1990; Maldjian et al, 1999; Mazza et al, 2006, 2013; Parra-Saavedra et al, 2011), and theoretical mechanics (Liao et al, 2014; Myers and Ateshian, 2014; Paskaleva, 2007). At the present time, there is no single set of correlating geometric and material property data from a single pregnant patient throughout gestation.…”

“…Human tissue tests reveal that the dense collagenous core of the cervix is similar to other load-bearing soft tissues in that its material response to loading is anisotropic, nonlinear, and time-dependent. The main features of cervical tissue behavior are: (1) term pregnant tissue is orders of magnitude softer than nonpregnant tissue (Table 1), (2) pregnant tissue has a higher hydraulic permeability compared to nonpregnant tissue (Fernandez et al, 2013), (3) the tensile stress response to deformation is larger than the compression response (Myers et al, 2008, 2010, 2015; Yao et al, 2014), (4) tissue displays a large amount of stress relaxation after a ramp-hold in deformation (Myers et al, 2008, 2010; Petersen et al, 1991; Yao et al, 2014), and (5) there is a large range in tissue properties between patients due to diverse obstetric backgrounds (as seen in Table 1) Myers et al, 2008, 2010; Oxlund et al, 2010a,b; Yao et al, 2014. Continued mechanical testing is needed to determine the extent of anisotropy, heterogeneity, and time-dependent visco- or poroelastic deformation mechanisms on the material behavior of the tissue at different length and time scales.…”

Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies

“…Magnuson and colleagues noted that fibronectin, a key component of ECM, undergoes changes in alternative splicing with aging both in vitro and in vivo, but that these changes are tissue specific. 73 Furthermore, it has been reported that the collagen content of human tissue increases with age in the left ventricle (LV) and uterine cervix, 74 but decreases in spinal discs. 75 Consequently, we divide our review of age-associated compositional modifications to the ECM by tissue type.…”

Ex vivo ultrasound attenuation coefficient for human cervical and uterine tissue from 5 to 10MHz

“…However, conventional ultrasound imaging cannot reliably differentiate myometrial abnormalities such as adenomyosis and leiomyomas, or endometrial abnormalities such as hyperplasia, polyps, and cancer (21, 25). Measurement of the stiffness (26–29) and acoustic (30–35) properties of the cervix and uterus and associated pathologies may provide important insights on ability to differentiate between tissue types.…”