ArticleCellular and molecular life sciences : CMLS2023
Developmental reprogramming of myometrial stem cells by endocrine disruptor linking to risk of uterine fibroids.
Article in Cellular and molecular life sciences : CMLS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Phthalate Metabolite, Mono(2-Ethyl-5-Hydroxyhexyl) Phthalate (MEHHP), Promotes Uterine-Fibroid-Associated Phenotypes in Myometrial Stem Cell-Derived 3D Organoids.Environmental toxicology · 2026Article
- Epigenetic Regulation of Uterine Smooth Muscle Tumors: Histone Modifications in Uterine Fibroids and Leiomyosarcoma.Biology · 2026Review
- Association between combined exposure to organochlorine pesticides and history of uterine fibroids in NHANES: findings from four statistical models.BMC public health · 2025Article
- Hair Straightener Use in Relation to Prevalent and Incident Fibroids in the Sister Study with a Focus on Black Women.Environmental health perspectives · 2025Article
- Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy.Cells · 2024Review
- Bromodomain-Containing Protein 9 Regulates Signaling Pathways and Reprograms the Epigenome in Immortalized Human Uterine Fibroid Cells.International journal of molecular sciences · 2024Article
- Racial disparities between measures of area deprivation and financial toxicity, and uterine volume in myomectomy patients.BMC women's health · 2023Article
- The adverse role of endocrine disrupting chemicals in the reproductive system.Frontiers in endocrinology · 2023Review
- Endocrine-disrupting chemicals and epigenetic reprogramming in developmental origin of uterine fibroids.Science progressArticle
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe stage, when tissues and organs are growing, is very vulnerable to environmental influences, but it's not clear how exposure during this time causes changes to the epigenome and increases the risk of hormone-related illnesses like uterine fibroids (UFs).
methodsDevelopmental reprogramming of myometrial stem cells (MMSCs), the putative origin from which UFs originate, was investigated in vitro and in the Eker rat model by RNA-seq, ChIP-seq, RRBS, gain/loss of function analysis, and luciferase activity assays.
resultsWhen exposed to the endocrine-disrupting chemical (EDC) diethylstilbestrol during Eker rat development, MMSCs undergo a reprogramming of their estrogen-responsive transcriptome. The reprogrammed genes in MMSCs are known as estrogen-responsive genes (ERGs) and are activated by mixed lineage leukemia protein-1 (MLL1) and DNA hypo-methylation mechanisms. Additionally, we observed a notable elevation in the expression of ERGs in MMSCs from Eker rats exposed to natural steroids after developmental exposure to EDC, thereby augmenting estrogen activity.
conclusionOur studies identify epigenetic mechanisms of MLL1/DNA hypo-methylation-mediated MMSC reprogramming. EDC exposure epigenetically targets MMSCs and leads to persistent changes in the expression of a subset of ERGs, imparting a hormonal imprint on the ERGs, resulting in a "hyper-estrogenic" phenotype, and increasing the hormone-dependent risk of UFs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.