Although not well deined, changes in proteoglycan composition are also suggested to accompany cervical ripening. At least three small leucinerich proteoglycans are expressed in the cervix-decorin, biglycan, and ibromodulin (Westergren-Thorsson, 1998). In other connective tissues, decorin interacts with collagen to regulate the packing, order, and strength of collagen fibrils (see Fig. 21-9) (Ameye, 2002). In addition to the cervix, these proteoglycans are expressed in the fetal membranes and uterus.
Inflammatory Changes. In phase 2, resident immune cells are localized to the cervical stroma, although a functional role for these cells in this phase of remodeling has been challenged. Microarray studies comparing gene to allow a gradual increase in mechanical compliance of the cervix, A collagen fiber is made up of many fibrils, Fibril size and packing are regulated in part by small proteoglycans such as ,,obefore and after cervical ripening decorln and by the denSity of collagen cross-links, In phase 1, fibril size is uniform and fibrils are veil organizedoalthough a decline in cross-link density aids softening, During cervical ripening show little rise in proinflammatory ,: ,o,
In phase 2, fibril size IS less uniform, and spacing between collagen fibrils and fibers is greater gene expression. In contrast, proinand disorganized, flammatory and immunosuppressive gene expression in the cervix after delivery increases markedly compared with that during cervical ripening (Bollapragada, 2009; Hassan, 2006, 2009). Further, detailed studies in mice provide evidence that leukocyte migration but not activation takes place before labor. Once labor is underway, activation of neutrophils, pro inflammatory M 1 macrophages, and tissue repair M2 macrophages in the cervix is augmented. This suggests a role for inlammatory cells in postpartum cervical remodeling and repair (Mahendroo, 2012).
Induction of Cervical Ripening
No therapies prevent premature cervical ripening. In contrast, treatment to promote cervical ripening for labor induction includes direct application of prostaglandins PGE2 and PGF2'. Prostaglandins likely modiy extracellular matrix structure to aid ripening. Although the role of prostaglandins in the normal physiology of cervical ripening remains unclear, this property is useful clinically to assist labor induction (Chap. 26, p. 505).
In some nonhuman species, the cascades of events that allow cervical ripening are induced by dropping serum progesterone concentrations. And in humans, administration of progesterone antagonists causes cervical ripening.
In addition to matrix changes, during pregnancy, endocervical epithelial cells proliferate such that endocervical glands account for a signiicant percentage of cervical mass. he endocervical canal is lined with mucus-secreting columnar and stratified squamous epithelia. These cells form both a mucosal barrier and a tight junctional barrier that protect against microbial invasion (Akgul, 2014; Blaskewicz, 2011; Timmons, 2007). The mucosal epithelium recognizes and deters pathogen invasion via expression of toll-like receptors that identiy pathogens and via antimicrobial pep tides and protease inhibitors. In addition, these epithelia express signals to underlying immune cells when a pathogenic challenge exceeds their protective capacity (Wira, 2005).
• Fetal Contributions to Parturition