The physiology of cervical ripening and cervical dilatation and the effect of abortifacient drugs

Abstract

The mechanical properties of the human uterine cervix are determined mainly by the connective tissue component, whereas it is doubtful whether the scanty smooth muscle component is of any physiological importance. Histological and biochemical analyses reveal a fibrous connective tissue similar to that found in skin and tendon. Degradation of the collagen and an increase in some special dermatan sulphate proteoglycans can at least partly explain the pregnancy-associated softening of this connective tissue. Relatively high oestrogen levels seem to be an absolute condition for the process, even when it is induced pharmacologically. Treatment with progesterone-receptor blockers, PGE2, PGF2 alpha or relaxin in pregnancy induce cervical softening as well as histological and biochemical changes which cannot be distinguished from the physiological cervical softening which takes place in late pregnancy. Prostaglandins and relaxin might interact and could include cytokines such as interleukin-1 during the process. The effect of cervical tents cannot be explained only by the radial pressures they exert. Most probably stimulation of local prostaglandin synthesis is also involved.

PIP: Cervical ripening is reviewed from the viewpoint of mechanical properties, histological and biochemical structure of cervical tissue, and the role of hormones and other bioactive agents in the process. The uterine cervix begins abruptly with a 2-3 mm transition from the myometrium and is made of 80% type I collagen and 20% type III collagen fibers covalently cross linked, and glycosaminoglyucans covalently bound to protein cores. During pregnancy the collagen concentration is halved and its extractability increases due to changes in the proteoglycan composition, an increase in acidic relative to neutral proteins. These changes are responsible for the softening of the cervix (Goodell's sign) and the isthmus (Hegar's sign). Histologically the collagen fibers appear thinner and more spread out. Polymorphonuclear leukocytes and eosinophils may be involved in the softening process. Factors theorized or know to be involved in cervical ripening are progesterone, estradiol, prostaglandins (PGs), relaxin, and cytokines. Progesterone withdrawal has been shown in animal models. Estradiol either induces PG synthesis or sensitizes the cervix to locally produced PGs. PGE2 and PGF2alpha receptors have been found in cervical plasma membranes, have been isolated from tissue, their local synthesis can be manipulated, and their clinical use is well documented. Relaxin is a peptide synthesized in the corpus luteum, uterus and placenta, and is known to relax the pelvic girdle, restrain myometrial activity and soften the cervix. Cytokines such as interleukin-1 and tumor necrosis factor are being studies because of their ability to stimulate collagenase.