ArticleCell & bioscience2022
Myometrial oxidative stress drives MED12 mutations in leiomyoma.
Article in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The relationship between fat-soluble vitamins and uterine fibroids: a systematic review.BMC women's health · 2025Pooled it
- The estrogen-progestogen-oxidative stress network in uterine fibroids: mechanistic insights and therapeutic opportunities.Redox report : communications in free radical research · 2026Review
- Phthalate Metabolite, Mono(2-Ethyl-5-Hydroxyhexyl) Phthalate (MEHHP), Promotes Uterine-Fibroid-Associated Phenotypes in Myometrial Stem Cell-Derived 3D Organoids.Environmental toxicology · 2026Article
- Review
- Article
- Human Myometrial Cell Fate under Chronic Oxidative Stress for Leiomyomagenesis.Research square · 2026Article
- Review
- Body Mass Index and Uterine Fibroid Development: A Prospective Study.The Journal of clinical endocrinology and metabolism · 2024Article
- Altered extracellular matrix-related pathways accelerate the transition from normal to prefibroid myometrium in Black women.American journal of obstetrics and gynecology · 2024Article
- SomaticCells · 2024Article
- Hypoxia in uterine fibroids: role in pathobiology and therapeutic opportunities.Oxygen (Basel, Switzerland) · 2024Article
- Racial disparity in uterine leiomyoma: new insights of genetic and environmental burden in myometrial cells.Molecular human reproduction · 2024Review
- Identification of oxidative stress-related biomarkers in uterine leiomyoma: a transcriptome-combined Mendelian randomization analysis.Frontiers in endocrinology · 2024Article
- Association of genital talc and douche use in early adolescence or adulthood with uterine fibroids diagnoses.American journal of obstetrics and gynecology · 2023Article
- Article
- Racial differences in transcriptomics and reactive oxygen species burden in myometrium and leiomyoma.Human reproduction (Oxford, England) · 2023Article
- Oxidative Stress and Antioxidants in Uterine Fibroids: Pathophysiology and Clinical Implications.Antioxidants (Basel, Switzerland) · 2023Review
- Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas.International journal of molecular sciences · 2023Article
- Mono-(2-ethyl-5-hydroxyhexyl) phthalate promotes uterine leiomyoma cell survival through tryptophan-kynurenine-AHR pathway activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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8 authors.
Funding
Abstract
backgroundMore than 70% of leiomyomas (LM) harbor MED12 mutations, primarily in exon 2 at c.130-131(GG). The cause of MED12 mutations in myometrial cells remains largely unknown. We hypothesized that increased ROS promotes MED12 mutations in myometrial cells through the oxidation of guanine nucleotides followed by misrepair.
methodsGenomic oxidative burden (8-OHdG) was evaluated in vitro and in vivo by immunohistochemistry. MED12 mutations were examined by Sanger sequencing and deep sequencing. Transcriptome examined by RNA-seq was performed in myometrium with and without LM, in primary myometrial cells treated with ROS. 8-OHdG mediated misrepair was analyzed by CRISPR/Cas9.
resultsUteri with high LM burden had a significantly higher rate of MED12 mutations than uteri with low LM burden. Compelling data suggest that the uterus normally produces reactive oxidative species (ROS) in response to stress, and ROS levels in LM are elevated due to metabolic defects. We demonstrated that genomic oxidized guanine (8-OHdG) was found at a significantly higher level in the myometrium of uteri that had multiple LM compared to myometrium without LM. Transcriptome and pathway analyses detected ROS stress in myometrium with LM. Targeted replacement of guanine with 8-OHdG at MED12 c.130 by CRISPR/Cas9 significantly increased the misrepair of G>T. Exposure of primary myometrial cells to oxidative stress in vitro increased misrepair/mutations as detected by duplex sequencing.
conclusionsTogether, our data identified a clear connection between increased myometrial oxidative stress and a high rate of MED12 mutations that may underlie the risk of LM development and severity in women of reproductive age.
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