Abstract
Uterine leiomyomas (fibroids) are the most common non-cancerous tumors affecting women. Psychosocial stress is associated with fibroid risk and severity. The relationship between psychosocial stress and fibroid pathogenesis may involve alterations in microRNAs (miRNAs) although this has yet to be examined. We investigated associations between two psychosocial stress measures, a composite measure of recent stressful life events and perceived social status, with expression levels of 401 miRNAs in myometrium (n = 20) and fibroids (n = 44; 20 with paired fibroid and myometrium samples) among pre-menopausal women who underwent surgery for fibroid treatment. We used linear regressions to identify psychosocial stressors associated with miRNAs, adjusting for covariates (age, body mass index, race/ethnicity, and oral contraceptive use). The association between psychosocial stressors and miRNAs was considered statistically significant at an FDR p < 0.10 and showed a monotonic response (nominal p-trend < 0.05). In the myometrium, 21 miRNAs were significantly associated with a composite measure of recent stressful events, and two miRNAs were associated with perceived social status. No fibroid miRNAs were associated with either stress measure. Pathway analyses revealed miRNA-mRNA targets were significantly enriched (FDR p < 0.05) in pathways relevant to cancer/tumor development. Of the 74 differentially expressed miRNAs between myometrium and fibroids, miR-27a-5p and miR-301b were also associated with stress exposure. Our pilot analysis suggests that psychosocial stress is associated with myometrial miRNA expression and, thus, may have a role in the pathogenesis of fibroids from healthy myometrium.
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Data Availability
The data that supports findings from this study are available upon reasonable request from ARZ. The data is part of a larger on-going collection for the FORGE study and is currently not publicly available.
Code Availability
Code required for this study using R studio (version 4.1) will be available upon request.
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Acknowledgements
The authors would like to thank the FORGE study participants and study team, without your help, none of this work would have been made possible. We acknowledge Dr. James Robinson, Dr. Jessica Opoku-Anane, and Dr. Maria (Vicky) Vargas for their assistance with study design and recruitment of study participants. We acknowledge Susanna Mitro, Tyiesha Johnson, Angela Stoehr, Darah Wright, and Brenda Trejo who contributed to participant recruitment, data collection, and database management.
Funding
This work was supported by the National Institutes of Child Health and Development R21HD096248 (AZ), the National Institute of Environmental Health Sciences: P30ES009089 (AZ), T32ES007322 (CKD) and R01ES032638-03 (CKD), the George Washington University Milken School of Public Health (AZ), and the George Washington University Office of the Vice President for Research (Cross-disciplinary Research Fund)(AZ).
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Christian K. Dye: data analysis and manuscript authorship (writing, reviewing, editing, and figures/tables/legends); Haotian Wu: miRNA processing and data analysis; Brianna VanNoy: data collection and access; Stephanie Calluori: writing, revising, and interpretation; Cherie Q. Marfori: study design and interpretation; Andrea A. Baccarelli: miRNA interpretation, study design, interpretation, writing revision, and supervision; Ami R. Zota: conceptualization, study design, interpretation, supervision, and manuscript authorship (writing, reviewing, and editing). All authors reviewed and approved the final manuscript.
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Dye, C.K., Wu, H., VanNoy, B. et al. Psychosocial Stress and MicroRNA Expression Profiles in Myometrial Tissue of Women Undergoing Surgical Treatment for Uterine Fibroids. Reprod. Sci. 31, 1651–1661 (2024). https://doi.org/10.1007/s43032-024-01482-2
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DOI: https://doi.org/10.1007/s43032-024-01482-2