Objectives: The timely onset of powerful uterine contractions during parturition involves the integration of many signaling pathways, the protein components of which may be translationaly regulated throughout gestation. We have utilized the pregnant mouse model to examine gestational-dependent changes in the expression of several proteins implicated in the coordination of myometrial excitation-contraction coupling: caveolins 1-3, rho-associated kinases (ROKalpha and beta), alpha-actin, MLC(20), and h-caldesmon.
Methods: Protein expression was examined by Western blotting of myometrial homogenates from nonpregnant mice (NP) and compared to that from pregnant mice on gestational days 12, 15, 17, and 19 (term = day 19).
Results: All protein expressions were unchanged during the estrous cycle. alpha-Actin was found to be invariant throughout pregnancy. The expressions of caveolin-1, -2 and -3, when compared to alpha-actin expression, also did not change significantly with mid- to late pregnancy. h-caldesmon: alpha-actin, ROKalpha:alpha-actin, and ROKbeta:alpha-actin ratios were, however, significantly elevated on day 19, whereas MLC(20):alpha-actin was significantly down-regulated on day 12 to day 19. Consistent with elevated ROK expression at term, the ROK inhibitor Y27632 gave a greater reduction of thromboxane-stimulated contractions in myometrium from day 19 mice compared to NP mice.
Conclusions: These data suggest that in mouse myometrium there is a dynamic regulation of the expression of several proteins implicated in contractile signal integration. This may be important for regulating (1) relative uterine quiescence to ensure pregnancy progression and (2) priming the tissue for requisite contractile effort at term.