Oestradiol affects skeletal muscle mass, strength and satellite cells following repeated injuries

New Findings: What is the central question of this study? Oestradiol (E₂) plays an important role in regulating skeletal muscle strength in females. To what extent does E₂ deficiency affect recovery of strength and satellite cell number when muscle is challenged by multiple injuries? What is the main finding and its importance? E₂ deficiency impairs the adaptive potential of skeletal muscle following repeated injuries, as measured by muscle mass and strength. The impairment is likely multifactorial with our data indicating that one mechanism is reduction in satellite cell number. Our findings have implications for ageing, hormone replacement and regenerative medicine in regards to maintaining satellite cell number and ultimately the preservation of skeletal muscle's adaptive potential. Abstract: Oestradiol's effects on skeletal muscle are multifactorial including the preservation of mass, contractility and regeneration. Here, we aimed to determine the extent to which oestradiol deficiency affects strength recovery when muscle is challenged by multiple BaCl₂-induced injuries and to assess how satellite cell number is influenced by the combination of oestradiol deficiency and repetitive skeletal muscle injuries. A longitudinal study was designed, using an in vivo anaesthetized mouse approach to precisely and repeatedly measure maximal isometric torque, coupled with endpoint fluorescence-activated cell sorting to quantify satellite cells. Isometric torque and strength gains were lower in ovariectomized mice at several time points after the injuries compared to those treated with 17β-oestradiol. Satellite cell number was 41–43% lower in placebo- than in oestradiol-treated ovariectomized mice, regardless of injury status or number of injuries. Together, these results indicate that the loss of oestradiol blunts adaptive strength gains and that the number of satellite cells likely contributes to the impairment.