By F Petraglia; Society for Gynecologic Investigation
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Extra info for Preterm birth: mechanisms, mediators, prediction, prevention, and interventions
Although not studied in detail, it is likely that anti-inflammatory pathways (also activated during parturition) facilitate re-formation of the cervix in the puerperium. 5 are well-established, and some are under active investigation in various laboratories. 93,95 Mechanical stretch also activates NFB signaling in fibroblasts,107,108 and would further compromise progesterone receptor function. 5 Proposed regulation of cervical function during pregnancy and parturition. Cervical competency (A) is maintained by interactions between progesterone receptors (PR) and other transcriptional complexes to induce anti-inflammatory events including suppression of transforming growth factor (TGF) ␤ signaling through the downstream effectors of TGF-␤ signaling; Smad2 or -3 (R-Smad) are activated and phosphorylated upon TGF-␤ binding to type I and II receptors.
Two isoenzymes exist, COX-1, or the constitutive form, and COX-2, the inducible isoenzyme. These enzymes are responsible for the ratelimiting step in prostaglandin biosynthesis. COX-2 is upregulated by various growth factors and cytokines, and has been shown in most studies to be increased in the cervix during parturition. 23 It has been suggested that this enzyme is also elevated in Chap-02:Preterm 11/17/2006 9:25 AM Page 26 26 PRETERM BIRTH myometrial tissues from women in labor. We (Havelock et al43) and others63 have shown that COX-2 mRNA is not significantly different in fundal myometrial specimens from laboring and nonlaboring women whether obtained at the time of Cesarean section or Cesarean hysterectomy.
The third phase, involving leukocytes and release of proteases into the extracellular matrix, accompanies cervical dilation during labor. Although the term cervical ripening is often used interchangeably to describe changes in the cervix that occur before and during labor, it appears that changes of the cervix during dilation of the cervix in active labor involve different processes to those of cervical ripening before labor. The fourth and final phase of cervical remodeling occurs after parturition (during uterine involution), with a rapid recovery phase involving resolution of inflammation and re-formation of the dense connective tissue and structural integrity of the cervix.