Sex differences in muscle health in simulated micro- and partial-gravity environments in rats

Abstract

Skeletal muscle size and strength are important for overall health for astronauts. However, how male and female muscle may respond differently to micro- and partial-gravity environments is not fully understood. The purpose of this study was to determine how biological sex and sex steroid hormones influence the progression of muscle atrophy after long term exposure to micro and partial gravity environments in male and female rats. Male and female Fisher rats (n ​= ​120) underwent either castration/ovariectomy or sham surgeries. After two weeks recovery, animals were divided into microgravity (0g), partial-gravity (40% of weight bearing, 0.4g), or full weight bearing (1g) interventions for 28 days. Measurements of muscle size and strength were evaluated prior to and after interventions. At 0g, females lost more dorsiflexion strength, plantar flexion strength, and other metrics of muscle size compared to males; castration/ovariectomy did not influence these differences. Additionally, at 0.4g, females lost more dorsiflexion strength, plantar flexion strength, and other metrics of muscle strength compared to males; castration/ovariectomy did not influence these differences. Females have greater musculoskeletal aberrations during exposure to both microgravity and partial-gravity environments; these differences are not dependent on the presence of sex steroid hormones. Correspondingly, additional interventions may be necessary to mitigate musculoskeletal loss in female astronauts to protect occupational and overall health.

Keywords: Atrophy; Dorsiflexion; Muscle strength; Plantar flexion; Sex differences.

Fig. 1

Bodyweight and grip strength changes in males and females undergoing exposure to micro-gravity (0g) or 40% partial-gravity (0.4g) interventions in SHAM and CAST/OVX conditions. Bodyweight changes in A) SHAM males and females exposed to 0g. B) CAST males and OVX females exposed to 0g. C) SHAM males and females exposed to 0.4g. D) CAST males and OVX females exposed to 0.4g. Grip strength changes in E) SHAM males and females exposed to 0g. F) CAST males and OVX females exposed to 0g. G) SHAM males and females exposed to 0.4g. H) CAST males and OVX females exposed to 0.4g. Individual data points are percent difference between pre-intervention and post-intervention (28 days) with a covariate of baseline values. Data are presented as Mean ​± ​SEM. SHAM ​= ​sham surgery animals with intact gonads, CAST ​= ​castrated males, OVX ​= ​ovariectomized females, SEM ​= ​standard error of the mean.

Fig. 2

Leg girth and total muscle area changes in the lower leg between males and females undergoing exposure to micro-gravity (0g) or 40% partial-gravity (0.4g) interventions in both SHAM and CAST/OVX conditions. Leg girth changes in A) SHAM males and females exposed to 0g. B) CAST males and OVX females exposed to 0g. C) SHAM males and females exposed to 0.4g. D) CAST males and OVX females exposed to 0.4g. Muscle area changes in E) SHAM males and females exposed to 0g. F) CAST males and OVX females exposed to 0g. G) SHAM males and females exposed to 0.4g. H) CAST males and OVX females exposed to 0.4g. Individual data points are percent difference between pre-intervention and post-intervention (28 days) with a covariate of baseline values. Data are presented as Mean ​± ​SEM. SHAM ​= ​sham surgery animals with intact gonads, CAST ​= ​castrated males, OVX ​= ​ovariectomized females, SEM ​= ​standard error of the mean.

Fig. 3

Muscle fiber cross-sectional area (CSA) differences in the soleus muscle between males and females undergoing exposure to micro-gravity (0g) or 40% partial-gravity (0.4g) interventions in both SHAM and CAST/OVX conditions. Overall CSA differences in A) SHAM males and females exposed to 0g. B) CAST males and OVX females exposed to 0g. C) SHAM males and females exposed to 0.4g. D) CAST males and OVX females exposed to 0.4g. Type I CSA differences in E) SHAM males and females exposed to 0g. F) CAST males and OVX females exposed to 0g. G) SHAM males and females exposed to 0.4g. H) CAST males and OVX females exposed to 0.4g. Type II CSA differences in I) SHAM males and females exposed to 0g. J) CAST males and OVX females exposed to 0g. K) SHAM males and females exposed to 0.4g. L) CAST males and OVX females exposed to 0.4g. Hybrid Type I/Type II CSA differences in M) SHAM males and females exposed to 0g. N) CAST males and OVX females exposed to 0g. O) SHAM males and females exposed to 0.4g. P) CAST males and OVX females exposed to 0.4g. Q) Representative images for all groups. All images collected at 20× magnification, scale bars represent 50 ​μm (micrometers). Individual data points are percent difference from within sex and hormone-status 1g (fully loaded) control animals. Data are presented as Mean ​± ​SEM. SHAM ​= ​sham surgery animals with intact gonads, CAST ​= ​castrated males, OVX ​= ​ovariectomized females, SEM ​= ​standard error of the mean.

Fig. 4

Dorsiflexion and plantar flexion power production between males and females undergoing exposure to micro-gravity (0g) or 40% partial-gravity (0.4g) interventions in both SHAM and CAST/OVX conditions. Dorsiflexion power changes in A) SHAM males and females exposed to 0g. B) CAST males and OVX females exposed to 0g. C) SHAM males and females exposed to 0.4g. D) CAST males and OVX females exposed to 0.4g. Plantar flexion power loss in E) SHAM males and females exposed to 0g. F) CAST males and OVX females exposed to 0g. G) SHAM males and females exposed to 0.4g. H) CAST males and OVX females exposed to 0.4g. Individual data points are percent difference between pre-intervention and post-intervention (28 days) with a covariate of baseline values. Data are presented as Mean ​± ​SEM. SHAM ​= ​sham surgery animals with intact gonads, CAST ​= ​castrated males, OVX ​= ​ovariectomized females, SEM ​= ​standard error of the mean.

Fig. 5

Hindlimb muscle mass differences between males and females undergoing exposure to micro-gravity (0g) or 40% partial-gravity (0.4g) interventions in both sham and castrated/ovariectomized conditions. Percent difference gastrocnemius mass in A) SHAM males and females exposed to 0g. B) CAST males and OVX females exposed to 0g. C) SHAM males and females exposed to 0.4g. D) CAST males and OVX females exposed to 0.4g. Percent difference soleus mass in E) SHAM males and females exposed to 0g. F) CAST males and OVX females exposed to 0g. G) SHAM males and females exposed to 0.4g. H) CAST males and OVX females exposed to 0.4g. Percent difference in tibialis anterior mass in I) SHAM males and females exposed to 0g. J) CAST males and OVX females exposed to 0g. K) SHAM males and females exposed to 0.4g. L) CAST males and OVX females exposed to 0.4g. Percent difference extensor digitorum longus (EDL) mass in M) SHAM males and females exposed to 0g. N) CAST males and OVX females exposed to 0g. O) SHAM males and females exposed to 0.4g. P) CAST males and OVX females exposed to 0.4g. Individual data points are percent difference from within sex and hormone-status 1g (fully loaded) control animals. Data are presented as Mean ​± ​SEM. SHAM ​= ​sham surgery animals with intact gonads, CAST ​= ​castrated males, OVX ​= ​ovariectomized females, SEM ​= ​standard error of the mean.