Myometrial mechanoadaptation during pregnancy: implications for smooth muscle plasticity and remodelling

The smooth muscle of the uterus during pregnancy presents a unique circumstance of physiological mechanotransduction as the tissue remodels in response to stretches imposed by the growing foetus(es), yet the nature of the molecular and functional adaptations remain unresolved. We studied, in myometrium isolated from non-pregnant (NP) and pregnant mice, the active and passive length-tension curves by myography and the expression and activation by immunoblotting of focal adhesion-related proteins known in other systems to participate in mechanosensing and mechanotransduction. In situ uterine mass correlated with pup number and weight throughout pregnancy. In vitro myometrial active, and passive, length-tension curves shifted significantly to the right during pregnancy indicative of altered mechanosensitivity; at term, maximum active tension was generated following 3.94+/-0.33-fold stretch beyond slack length compared to 1.91+/-0.12-fold for NP mice. Moreover, mechanotransduction was altered during pregnancy as evidenced by the progressive increase in absolute force production at each optimal stretch. Pregnancy was concomitantly associated with an increased expression of the dense plaque-associated proteins FAK and paxillin, and elevated activation of FAK, paxillin, c-Src and extracellular signal-regulated kinase (ERK1/2) which reversed 1 day post-partum. Electron microscopy revealed close appositioning of neighbouring myometrial cells across a narrow extracellular cleft adjoining plasmalemmal dense plaques. Collectively, these results suggest a physiological basis of myometrial length adaptation, long known to be a property of many smooth muscles, whereupon plasmalemmal dense plaque proteins serve as molecular signalling and structural platforms contributing to functional (contractile) remodelling in response to chronic stretch.