ArticleStem cell reviews and reports2022
Mice Uterine Stem Cells are Affected by Neonatal Endocrine Disruption & Initiate Uteropathies in Adult Life Independent of Circulatory Ovarian Hormones.
Article in Stem cell reviews and reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Relationship Between VSELs, MUSE Cells and MSCs in Health and Disease.Stem cell reviews and reports · 2026Review
- The consequences of the extremely low frequency electromagnetic field (ELF-EMF) exposure on physiological processes in the uterus: novel insights and implications.Frontiers in physiology · 2026Review
- Dysfunctional, Tissue-Resident, Very Small Embryonic-Like Stem Cells (VSELs) Initiate Cancer and Result in its Progression and Metastasis, Independent of Epithelial-Mesenchymal Transition.Stem cell reviews and reports · 2026Review
- Progesterone-induced activation of progesterone receptor alleviates alveolar bone resorption and inflammatory response in periodontitis.Clinical oral investigations · 2025Article
- Reversing Uteropathies Including Cancer-Like Changes in Mice by Transplanting Mesenchymal Stromal Cells or XAR Treatment.Stem cell reviews and reports · 2024Article
- Vascular Progenitor Cells: From Cancer to Tissue Repair.Journal of clinical medicine · 2023Review
- The adverse role of endocrine disrupting chemicals in the reproductive system.Frontiers in endocrinology · 2023Review
- Molecular Insights into Endometrial Cancer in Mice.Stem cell reviews and reports · 2022Article
- Additional evidence to support OCT-4 positive VSELs and EnSCs as the elusive tissue-resident stem/progenitor cells in adult mice uterus.Stem cell research & therapy · 2022Article
- Genetic Regulation of Transcription in the Endometrium in Health and Disease.Frontiers in reproductive health · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is generally believed that ovarian hormones regulate uterine functions and their altered levels result in various uteropathies like non-receptive uterus, endometrial hyperplasia, adenomyosis, endometriosis, leiomyomas and cancer. Uterus harbors two populations of stem cells including pluripotent, very small embryonic-like stem cells (VSELs) and tissue-specific progenitors (endometrial stem cells, EnSCs). Unlike endometrial mesenchymal stem/ stromal cells, VSELs/EnSCs express ERα, ERβ and PR which makes them directly vulnerable to perinatal endocrine insults. Present study was undertaken to evaluate whether uteropathies occur due to altered hormones and/or intrinsic changes in stem/progenitor cells. Mice pups, exposed to estradiol (20 µg/pup/day) on postnatal days 3-7 or vehicle, were subjected to bilateral ovariectomy on day 30 and later exposed sequentially to estradiol and progesterone resulting in receptive uterus in control mice. Despite similar hormonal exposure, endocrine disruption resulted in non-receptive uterus with noticeable endometrial and myometrial hyperplasia and up-regulation of stem cell markers (Oct-4A, Oct-4, Sox2, Nanog). Glands were poorly formed and 'defective' epithelial progenitors were found disseminated into myometrium and blood vessels revealing how adenomyosis and endometriosis possibly initiate. Progesterone resistance and estradiol dominance due to downregulation of Erα & Pr and upregulation of Erβ transcripts was observed in both intact uterus and stem cells enriched from uterus. Transcripts specific for DNA mismatch repair axis (Pcna, NP95 and Dnmt1), repair enzymes (Brca-1, Rad51 and Mlh1) were dysregulated whereas Ki67 was ten-folds increased suggestive of genomic instability. Study reveals role of stem cells in initiating uteropathies during adult life independent of circulatory ovarian hormones. Endocrine disruption affects tissue resident stem/progenitor cells (VSELs/EnSCs) in both endometrium and myometrium, result in epithelial cells hyperplasia, non-receptive endometrium, adenomyosis and defective stem cells and epithelial progenitors were detected in the perimetrium from where they can mobilize to ectopic sites to initiate endometriosis. Study shows stem cell basis for various uteropathies. VSEL: Very small embryonic like stem cell; EnSC: Endometrial stem cell; E + P: Estradiol + Progesterone; E: Endometrium; P: Perimetrium; M: Myometrium; ACD: Asymmetrical cell division; SCD: Symmetrical cell division; CE: Clonal expansion; G: Gland; S: Stromal cell; US: Undifferentiated stromal cell; LE: Luminal epithelium; GE: Glandular epithelium; EP: Epithelial progenitors; SMC: Spindle-shaped myometrial cell; OMC: Oval-shaped myometrial cell.
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