Cervical collagen and biomechanical strength in non-pregnant women with a history of cervical insufficiency

Abstract

BackgroundIt has been suggested that cervical insufficiency (CI) is characterized by a "muscular cervix" with low collagen and high smooth muscle concentrations also in the non-pregnant state. Therefore, the aim of this study was to investigate the biomechanical properties, collagen concentration, smooth muscle cell density, and collagen fiber orientation in cervical biopsies from non-pregnant women with a history of CI.MethodsCervical punch biopsies (2 × 15 mm) were obtained from 57 normal non-pregnant women and 22 women with a history of CI. Biomechanical tensile testing was performed, and collagen content was determined by hydroxyproline quantification. Histomorphometry was used to determine the volume densities of extracellular matrix and smooth muscle cells from the distal to the proximal part of each sample. Smooth muscle cells were identified using immunohistoche-mistry. Finally, collagen fiber orientation was investigated. Data are given as mean +/- SD.ResultsCollagen concentration was lower in the CI group (58.6 +/- 8.8%) compared with the control group (62.2 +/- 6.6%) (p = 0.033). However, when data were adjusted for age and parity, no difference in collagen concentration was found between the two groups. Maximum load of the specimens did not differ between the groups (p = 0.78). The tensile strength of cervical collagen, i.e. maximum load normalized per unit collagen (mg of collagen per mm of specimen length), was increased in the CI group compared with controls (p = 0.033). No differences in the volume density of extracellular matrix or smooth muscle cells were found between the two groups. Fibers not oriented in the plane of sectioning were increased in CI patients compared with controls.ConclusionsCervical insufficiency does not appear to be associated with a constitutionally low collagen concentration or collagen of inferior mechanical quality. Furthermore, the hypothesis that a "muscular cervix" with an abundance of smooth muscle cells contributes to the development of cervical insufficiency is not supported by the present study.

The mechanical role of the cervix in pregnancy

“…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.…”

Cervical collagen is reduced in non‐pregnant women with a history of cervical insufficiency and a short cervix

“…An inherent condition of biomechanical weakness may explain the cervical incompetence in these women. The weakness may be caused by a constitutional defect (11)(12)(13)(14)(15), congenital M€ ullerian anomalies (16), birth trauma (17), induced abortion (18) or conization (19)(20)(21)(22). Another hypothesis is that cervical insufficiency is associated with preterm ripening (13) caused by infection or an inappropriate inflammatory response (23,24).…”

“…Collagen concentration in cervical biopsies analyzed with or without epithelium. Four biopsies were obtained from each of 20 patients (participant ID numbers [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The biopsies were air-dried, after which they were soaked in isotonic saline.…”

Polymorphisms in Genes Coding for Cytokines, Mannose-Binding Lectin, Collagen Metabolism and Thrombophilia in Women with Cervical Insufficiency

“…Thus the cervical collagen concentration has been shown to be lower in women with a history of cervical insufficiency [4,5]. Congenital uterine malformation and surgery on the cervix including conization are other proposed causes of cervical insufficiency [6,7,8,9].…”