Sex Differences in Skeletal Muscle Force Production, Fatiguability and Recovery in Slow and Fast Twitch Muscles
Authors: Fletcher Nicole , Gee K. S. , Murrant C. L. 
Published: May 2022

Sex differences in skeletal muscle fatiguability have been well documented during isometric contractions in humans but whether this sexual dimorphism occurs in skeletal muscle at the cellular level is not well understood. Therefore, we aimed to determine if sex differences persisted in skeletal muscle function in isolated tissue. We hypothesized that sexual dimorphisms would not be apparent in twitch and tetanic contraction characteristics or fatigue and recovery of slow and fast twitch muscles. Soleus (SOL) and extensor digitorum longus (EDL) muscles were isolated from male and female CD‐1 mice. Muscle force production at optimal length was measured during 5 protocols: 1) force‐frequency relationship (1‐120Hz), 2) twitch contraction (1Hz), 3) non‐fatiguing contraction protocol (1 contraction/90sec, for 22.5 mins at submaximal (SOL‐25Hz; EDL‐50Hz) and maximal (SOL‐80Hz; EDL‐120Hz) stimulus frequencies), 4) fatiguing contraction protocols at submaximal and maximal stimulus frequencies using contraction frequencies of 15, 30, 45 and 60 contractions per min (cpm) over 5 mins and 5) recovery protocols (1contraction/90sec for 30 mins). The force‐frequency relationship revealed that females generated significantly larger force compared to males at stimulation frequencies of 10‐120Hz (SOL) and 30‐120Hz (EDL). Female SOL and EDL produced significantly higher forces during twitch contractions compared to males (SOL: male 27.8+/‐2.0 mN/mm2 vs. female 34.7+/‐2.4 mN/mm2; EDL: male 32.5+/‐2.1 mN/mm2 vs. female 41.2+/‐2.2 mN/mm2). No significant differences in time to peak contraction or time to half relaxation during the twitch were found between males and females. There were no differences in fatigue rates between male and female SOL or EDL during the non‐fatiguing contraction protocols. Fatiguing contraction protocols revealed that females were less fatiguable than males at submaximal stimulus frequencies at 30 and 45cpm (SOL) and at maximal stimulus frequencies at 45cpm (EDL). No significant differences in fatigue between males and females were found in the remaining 13 fatiguing contraction protocols. Significant differences between males and females in recovery protocols were found in only 4 of the 16 recovery protocols. Female SOL had less recovery of force compared to males at 25Hz at 30 and 45cpm, and at 80Hz at 45 and 60cpm. Collectively, these data demonstrate that there are sexual dimorphisms in absolute force production during twitch and a range of tetanic contractions in slow and fast twitch muscles. Although there were specific contraction parameters that showed enhanced fatigue resistance of females and less recovery of female slow twitch muscles, these findings were not systematic and not present in the vast majority of the fatigue/recovery protocols. Our data show that force production and fatiguability at the in vitro, cellular level cannot explain the in vivo observations in the literature and the lack of sexual dimorphisms present during the majority of fatigue/recovery protocols in vitro indicate that systemic influences may be driving these documented differences at the whole‐body level.