Uterine overdistension plays a key role in the onset of preterm labor associated with multiple gestations, polyhydramnios, and macrosomia. The mechanisms by which uterine overdistension might lead to preterm labor are not well understood. Uterine stretch induces the expression of gap junction proteins, such as CX-43 and CX-26 (Ou et al., 1997), as well as other contraction-associated proteins, such as oxytocin receptors (Terzidoo et al., 2005). In vitro stretch of myometrial strips also increases PGHS-2 and PGE (Sooranna et al., 2004). Stretching the muscle of the lower uterine segment has been shown to increase the levels of IL-8 and colla-
genase production, which in turn facilitates cervical ripening (Loudon et al., 2004; Maradny et al., 1996). The increased myometrial expression of PGHS-2 and IL-8 from uterine stretch appears to be mediated by activation of the MAPK system (Sooranna et al., 2005). An interaction between mechanical and endocrine signals during myometrial activation may exist; in vivo studies have shown increased levels of expression of CX-43 in response to mechanical stretch in an ovariectomized rat uterus, an effect that could be blocked by progesterone administration (Ou et al., 1998). Similarly, in rats uterine stretch has no effect on myometrial CX-43 expression in midpregnancy, probably as a result of the high levels of progesterone that are present at that time; progesterone withdrawal before the onset of labor allows stretch-induced CX-43 expression (Wathes and Porter, 1982).
The effect of uterine stretch on myometrial expression of G proteins (e.g., GsD), which mediate myometrial relaxation, is not known. Human studies of uterine overdistension are lacking. One recent study found no difference between singleton and multiple gestations in the levels of expression of GsD, PGE2 receptors, CX-43, and CX-26 in myometrium taken from nonlabor-ing women undergoing elective cesarean delivery at term (Lyall et al., 2002). Moreover, mechanical stretch did not alter the levels of GsD expression in vitro, and GsD expression was unaffected by steroid hormones. These findings suggest that the mechanisms by which uterine stretch can promote myometrial contractions in humans are complex and may involve additional factors or that multiple gestations that do not result in preterm labor may have compensatory mechanisms for the increased uterine stretch by preventing aberrant CAP expression.
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