Sex differences in skeletal muscle revealed through fiber type, capillarity, and transcriptomics profiling in mice

O'Reilly, Juliana; Ono‐Moore, Kikumi D.; Chintapalli, Sree V.; Rutkowsky, Jennifer; Tolentino, Todd; Lloyd, Kevin C K; Olfert, I. Mark; Adams, Sean H.

doi:10.14814/phy2.15031

Cited by 28 publications

(22 citation statements)

References 51 publications

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“…In a model of hind limb ischemia, AdipoR2 knockout mice showed delayed recovery of blood flow, impaired perfusion and reduced capillary density in the gastrocnemius muscle ( Parker-Duffen et al, 2014 ). Capillary density is strictly regulated in skeletal muscles in human and rodents, and the ratio depends on the muscle part ( O'Reilly et al, 2021 ; Høeg et al, 2009 ). Consistent with reduced Adipor2 expression in the DIA and TA muscles, the number of capillaries per muscle area and per myofiber were significantly decreased in the DIA and slightly decreased in the TA muscles of offspring rats exposed to gestational IH.…”

Section: Discussionmentioning

confidence: 99%

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

et al. 2023

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Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7–21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.

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Section: Discussionmentioning

confidence: 99%

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

et al. 2023

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“…The incidence of scoliosis in MSTN-OE-F mice was higher than that in MSTN-OE-M mice, which was similar to the prevalence characteristics of IS being more common in girls than in boys (Cai et al , 2021; Chung et al , 2020). These results may be related to the innate muscle sexual dimorphism in both mice and humans that lower muscle mass in the arms and trunk were observed in females (Abe et al , 2021; O’Reilly et al , 2021). Moreover, the body weight of bi-MSTN-OE mice was decreased compared with that of bi-CT mice, which was also consistent with the phenomenon that IS patients have lower body mass (Cai et al ., 2021).…”

Section: Resultsmentioning

confidence: 85%

Role of Paravertebral muscle myostatin upregulation in the development of idiopathic scoliosis

Zhang

Xiang

et al. 2022

Preprint

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Paravertebral muscle (PVM) abnormalities play important roles in the pathogenesis of idiopathic scoliosis (IS), and elevated oxidative stress could result in PVM injury in IS patients, but the underlying mechanism of oxidative stress generation is still unclear. Increased apoptosis, impaired myogenesis and elevated oxidative stress were found in primary skeletal muscle mesenchymal progenitor cells (hSM-MPCs), which are essential for the myogenesis process of vertebrate skeletal muscles, of IS patients. Through RNA-sequencing (RNA-seq) and further analysis, we identified significantly upregulated myostatin (MSTN) in IS hSM-MPCs. Overexpression of MSTN in hSM-MPCs from control patients increased the expression of NADPH oxidase 4, promoted reactive oxygen species production and apoptosis, and suppressed myogenesis. However, MSTN knockdown decreased the expression of NADPH oxidase 4, inhibited reactive oxygen species production and apoptosis, and enhanced myogenesis in hSM-MPCs from IS patients. In addition, overexpression of MSTN in the PVMs of mice induced elevated oxidative stress and scoliosis without abnormal vertebral structure. Altogether, our study suggested that abnormal PVM changes and accumulated oxidative stress in IS patients may result from upregulation of MSTN.

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“…Interestingly, the X-encoded paralogs ( Ddx3x, Utx, KDM5C ) were not different between the sexes, which may be due to X-chromosome inactivation ensuring dosage compensation across the sexes [64]. This finding adds to the existing evidence [65, 66] that sex differences originating from the sex chromosome complement seem to be conserved in primary cell lines [66]. Altogether, these data provide novel evidence that some sex-differences may be recapitulated in primary cell lines.…”

Section: Discussionmentioning

confidence: 81%

The influence of Sex on microRNA expression in Human Skeletal Muscle

Hiam

Landen

Michaux

et al. 2023

Preprint

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Introduction: Sex differences in microRNA (miRNA) expression profiles have been found across multiple tissues. Skeletal muscle is one of the top tissues that underpin sex-based differences, yet there is limited research into whether there are sex differences in miRNA expression in skeletal muscle. Further, there is limited literature investigating potential differences between males and females in skeletal muscle miRNA expression following exercise, a well-known modulator of miRNA expression. Therefore, the aim of this study was to investigate the effect of sex on miRNA expression in skeletal muscle at baseline and after an acute bout of exercise. Methods: MiRNAs were measured using Taqman miRNA arrays in skeletal muscle of 42 healthy participants from the GeneSMART study (24 males and 20 females aged 18-45 yrs). Differentially expressed miRNAs were identified using mixed linear models adjusted for age. Experimentally validated miRNA gene targets enriched in skeletal muscle were identified in-silico. Over representation analysis was conducted to identify enriched pathways. TransmiR V.2 was used to identify transcription factor (TF)-miR regulatory networks using CHIP-derived data. We further profiled the effects of two sex-biased miRNAs overexpressed in human primary muscle cells lines derived from male and female donors to understand the transcriptome targeted by these miRNAs and investigate and potential sex-specific effects. Results: A total of 80 miRNAs were differentially expressed in skeletal muscle between the sexes, with 61 miRNAs responding differently to the exercise between the sexes. Sex-biased miRNA gene targets were enriched for muscle-related processes including proliferation and differentiation of the muscle cells and numerous metabolic pathways, suggesting that miRNAs are playing a role in programming sex differences in skeletal muscle. Over-expression of sex-biased miRNAs miRNA-30a and miRNA-30c resulted in profound changes to gene expression profiles that were partly specific to the sex of the cell donor in human primary skeletal muscle cells. Conclusion: We found sex-differences in the expression profile of skeletal muscle miRNAs at baseline and in response to exercise. These miRNAs target regulatory pathways essential to skeletal muscle development and metabolism, suggesting that miRNAs play a profound but highly complex role in programming sex-differences in the skeletal muscle phenotype.

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Sex differences in skeletal muscle revealed through fiber type, capillarity, and transcriptomics profiling in mice

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 28 publications

References 51 publications

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

Role of Paravertebral muscle myostatin upregulation in the development of idiopathic scoliosis

The influence of Sex on microRNA expression in Human Skeletal Muscle

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