Investigating the temporal effects of ovarian failure on single muscle fibre contractility using a chemically-induced ovarian failure model in mice

We investigated the effects of chemically-induced ovarian failure on single fibre contractility of the soleus and extensor digitorum longus (EDL) muscles throughout ovarian failure, thereby mimicking the menopausal transition into late-stage menopause: [(D60;peri-menopause), (D120;onset of menopause), (D134;early-onset menopause), (D176;late-stage menopause)]. We used 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure in sexually-mature female mice. For the soleus at D120 and D176, mice with VCD-induced ovarian failure produced higher force as compared with controls (p<0.05). On D134, however, VCD had lower force production compared with controls (p<0.05). The cross-sectional area of the soleus fibres from the VCD group was larger at D120 compared with controls (p<0.05), but not at any other time point (p>0.05). The VCD group showed time-dependent changes in specific force production compared to controls, with a 37% decrease at D134 but a 39% increase at D176 in the soleus muscle (p<0.05). No differences in rate of force redevelopment (Ktr) or calcium sensitivity was observed for the soleus (p>0.05). For the EDL there were no differences in force, cross-sectional area, stiffness, Ktr, or calcium sensitivity between groups (p>0.05). Our results indicate that muscle contractility across the peri-menopausal transition into late-stage menopause is both muscle and phase-dependent, emphasizing the complexity of changing hormones throughout the lifespan on muscle contractile function.