The oestrous cycle and skeletal muscle atrophy: Investigations in rodent models of muscle loss

Abstract

Recent efforts have focused on improving our understanding of female muscle physiology during exposure to muscle atrophic stimuli. A key feature of female rodent physiology is the oestrous cycle. However, it is not known how such stimuli interact with the oestrous cycle to influence muscle health. In this study, we investigated the impact of muscle atrophic stimuli on the oestrous cycle and how these alterations are correlated with musculoskeletal outcomes. A series of experiments were performed in female rodents, including hindlimb unloading (HU), HU followed by 24 h of reloading, HU combined with dexamethasone treatment, and Lewis lung carcinoma.The oestrous cycle phase was assessed throughout each intervention and correlated with musculoskeletal outcomes. Seven or 14 days of HU increased the duration in dioestrus or metoestrus (D/M; low hormones) and was negatively correlated with gastrocnemius mass. Time spent in D/M was also negatively correlated with changes in grip strength and bone density after HU, and with muscle recovery 24 h after the cessation of HU. The addition of dexamethasone strengthened these relationships between time in D/M and reduced musculoskeletal outcomes. However, in animals with Lewis lung carcinoma, oestrous cyclicity did not differ from that of control animals, and time spent in D/M was not correlated with either gastrocnemius mass or tumour burden. In vitro experiments suggested that enhanced protein synthesis induced by estrogen might protect against muscle atrophy. In conclusion, muscle atrophic insults are correlated with changes in the oestrous cycle, which are associated with deterioration in musculoskeletal outcomes. The magnitude of oestrous cycle alterations depends on the atrophic stimuli.

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

“…The relationship between changes in estrous cycle and subsequent muscle size is supported by multiple prior studies across multiple conditions associated with muscle loss. 22 , 23 , 24 Regardless, our finding that presence of gonadal derived hormones does not solely mediate sex-based differences in the trajectory of musculoskeletal loss suggests that other factors in addition to gonadal hormones contribute to the observed sex differences. It is possible differences in chromosomal make-up between females and males (i.e.…”

Adaptation to full weight‐bearing following disuse in rats: The impact of biological sex on musculoskeletal recovery

“…Indeed, several studies have described the link between muscle atrophy and endocrine perturbations (Martín et al., 2018 ) and it has long been known that reductions in sex hormone levels (such as experienced after menopause or gonadectomy) are associated with greater musculoskeletal losses (Dupree & Dobs, 2004 ; Khadilkar, 2019 ; Navarrrete et al., 2020 ; Stratos et al., 2023 ). Recent experiments performed ex vivo and in vivo have shown that musculoskeletal deconditioning is directly correlated with the time spent in low‐hormonal phases (i.e., metestrus and diestrus) (Rosa‐Caldwell et al., 2021 ). In the current study, young adult females spent on average 57.8% of the time in low‐hormonal stages during HLS, similar to what has previously been reported (Rosa‐Caldwell et al., 2021 ).…”

“…Recent experiments performed ex vivo and in vivo have shown that musculoskeletal deconditioning is directly correlated with the time spent in low‐hormonal phases (i.e., metestrus and diestrus) (Rosa‐Caldwell et al., 2021 ). In the current study, young adult females spent on average 57.8% of the time in low‐hormonal stages during HLS, similar to what has previously been reported (Rosa‐Caldwell et al., 2021 ). However, during the week of reloading, they spent only 20.8% of the time in low‐hormonal stages, which represents a significant shift that could have facilitated musculoskeletal recovery.…”

“…Estrous cycle monitoring was performed daily around 8:00 am , as previously described (Caligioni, 2009 ; Rosa‐Caldwell et al., 2021 ). Briefly, a pipette tip containing 50 μL of ddH 2 O was gently inserted at the vaginal opening.…”

Non-alcoholic fatty liver disease in women – Current knowledge and emerging concepts

“…The fluctuation of oestradiol during the menstrual cycle (oestrus cycle in rodents) also does not seem to affect the muscle strength, fatiguability or power performance of young female athletes (n = 29) 116 or rodents. 117 Evidence to support the impact of menopause on muscle strength and muscle mass independent of ageing are equivocal and further research is needed to specify the contribution of menopause to sarcopenia. Nevertheless, sarcopenia and NAFLD remain closely linked, with each entity increasing the risk of the other and potentially being exacerbated by the menopause ( Fig.…”