Before contractions begin, the cervix must undergo extensive remodeling. his eventually leads to the cervix yielding and dilating from forceful uterine contractions. Cervical modiications during phase 2 principally involve connective tissue changes-termed cervical ripening. The transition from the softening to the ripening phase begins weeks or days before labor. During this transformation, the cervical matrix changes its total amounts of gycosaminogycans, which are large linear polysaccharides, and proteogycans, which are proteins bound to these glycosaminoglycans.
Many of the processes that aid cervical remodeling are controlled by the same hormones regulating uterine function. That said, the molecular events of each are varied because of diferences in cellular composition and physiological requirements. For example, the hormone relaxin regulates myometrial quiescence. It also regulates cervical ripening, but through cell proliferation and modulation of extracellular matrix components (Park, 2005; Soh, 2012). The uterine corpus is predominantly smooth muscle. In contrast, the cervix has a high ratio of ibroblasts to smooth muscle cells, and extracellular matrix contributes significantly to overall tissue mass. Recent studies in the nonpregnant human cervix report a spatial gradient of smooth muscle cells. Specifically, smooth muscle cells make up approximately 50 percent of stromal cells at the internal os but only 10 percent at the external os (Vink, 2016).
Collagen. The cervix is an extracellular-matrix-rich tissue. Constituents of the matrix include type I, III, and IV collagen, matricellular proteins, glycosaminoglycans, proteoglycans, and elastic ibers. Of these, collagen is largely responsible for the structural disposition of the cervix. During collagen assembly, multiple collagen triple-helical molecules are cross-linked to one another by the actions of lysyl oxidase to form ibrils. In addition, ibril size, packing, and organization determine the strength and mechanical properties of the cervix. These properties are regulated in part by collagen-binding proteoglycans such as decorin or biglycan, as well as matricellular proteins such as thrombospondin 2 (Fig. 21-9).
Higher turnover of collagen during pregnancy likely allows the gradual replacement of mature cross-linked collagen ibrils with poorly cross-linked ibrils, which yield greater collagen disorganization. his increased turnover, rather than loss of collagen to achieve cervical remodeling, is supported by mouse and human studies that document no changes in collagen content between nonpregnant states and term pregnancy (Akins, 201i1; Myers, 2008; Read, 2007; Yoshida, 2014). In further support, polymorphisms or mutations in genes required for collagen assembly are associated with an elevated incidence of cervical insuiciency (Anum, 2009; Rahman, 2003; Warren, 2007).
Glycosaminoglycans and Proteoglycans. Hyaluronan is a high-molecular-weight polysaccharide that functions alone, whereas most other glycosaminoglycans (GAGs) complex with proteins to form proteoglycans. Hyaluronan is a hydrophilic, space-illing molecule, and thus greater hyaluronan production during cervical ripening is thought to increase viscoelasticity, hydration, and matrix disorganization. Hyaluronan synthesis is carried out by hyaluronan synthase isoenzymes, and expression of these enzymes is elevated in the cervix during ripening (kgul, 2012; Straach, 2005).