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Author ORCID Identifier
https://orcid.org/0000-0002-8887-4487
Date Available
3-25-2028
Year of Publication
2026
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Health Sciences
Department/School/Program
Rehabilitation Sciences
Faculty
Esther Dupont-Versteegden
Faculty
Timothy Butterfield
Abstract
Skeletal muscle adapts to mechanical load by hypertrophy with use and atrophy with disuse. However, sex-specific differences in these responses, particularly during recovery, are poorly understood. This dissertation investigated how male and female rats respond to altered mechanical loading using hindlimb suspension (HS) to model disuse, reambulation (RA) for recovery, and mechanotherapy as an intervention. In study 1, females exhibited less atrophy during HS than males, associated with a smaller decline in myofibrillar protein synthesis (Ksyn). During recovery, females showed increased Ksyn, whereas males demonstrated reduced protein degradation (Kdeg). Mechanotherapy did not significantly alter fiber type, satellite cell, or myonuclear number. Study 2 used RNA sequencing to assess transcriptional responses. During HS, females showed greater metabolic gene expression, while males displayed increased inflammatory signaling and reduced mitochondrial gene expression. With recovery, females largely reversed disuse-induced changes and increased RNA synthesis. In contrast, males exhibited greater extracellular matrix remodeling, reduced ribosomal biogenesis, and decreased RNA degradation. Study 3 examined early (8-hour) recovery and single-cell transcription. Females showed more early gene changes, while fibro-adipogenic progenitors demonstrated stronger extracellular remodeling signatures in males. Overall, males and females differ in molecular responses to disuse and recovery, emphasizing the need for sex-specific therapeutic targets.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2026.20
Archival?
Archival
Funding Information
These studies were supported by the National Institutes of Health grants AT009268, AT009268-02S1, AT009268-05S1
Recommended Citation
Sklivas, Alexander, "RESPONSES OF SKELETAL MUSCLE TO CHANGES IN MECHANICAL LOAD ARE DIFFERENT BETWEEN MALES AND FEMALES" (2026). Theses and Dissertations--Rehabilitation Sciences. 113.
https://uknowledge.uky.edu/rehabsci_etds/113
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Medical Cell Biology Commons, Medical Physiology Commons, Musculoskeletal Diseases Commons, Musculoskeletal, Neural, and Ocular Physiology Commons, Physiological Processes Commons
