ArticleEndocrinology2019
Chronic Exposure of Mice to Bisphenol-A Alters Uterine Fibroblast Growth Factor Signaling and Leads to Aberrant Epithelial Proliferation.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Endocrine Disruptors and Endometrial Cancer: Molecular Mechanisms of Action and Clinical Implications, a Systematic Review.International journal of molecular sciences · 2022Pooled it
- Network toxicology and bioinformatic investigation of the association between Bisphenol A and endometrial cancer.Scientific reports · 2026Article
- Review
- Exposure to phthalates enhances estrogen and beta-catenin signaling pathways, leading to endometrial hyperplasia in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Impact of endocrine disrupting chemicals (EDCs) on epigenetic regulation in the uterus: a narrative review.Reproductive biology and endocrinology : RB&E · 2025Review
- Review
- Impact of Endocrine Disruptors on the Genitourinary Tract.Journal of xenobiotics · 2024Review
- The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA).Environmental health perspectives · 2024Article
- Prenatal exposure to nitrate alters uterine morphology and gene expression in adult female F1 generation rats.Archives of endocrinology and metabolism · 2024Article
- Exposure to select PFAS and PFAS mixtures alters response to platinum-based chemotherapy in endometrial cancer cell lines.Environmental health : a global access science source · 2023Article
- Invisible Hand behind Female Reproductive Disorders: Bisphenols, Recent Evidence and Future Perspectives.Toxics · 2023Review
- An Overview of the Health Effects of Bisphenol A from a One Health Perspective.Animals : an open access journal from MDPI · 2023Review
- The adverse role of endocrine disrupting chemicals in the reproductive system.Frontiers in endocrinology · 2023Review
- Bisphenol S Increases Cell Number and Stimulates Migration of Endometrial Epithelial Cells.Journal of the ASEAN Federation of Endocrine Societies · 2023Article
- Article
- Update on the Health Effects of Bisphenol A: Overwhelming Evidence of Harm.Endocrinology · 2021Review
- Bisphenol A (BPA) Affects the Enteric Nervous System in the Porcine Stomach.Animals : an open access journal from MDPI · 2020Article
- Low-Dose Bisphenol A in a Rat Model of Endometrial Cancer: A CLARITY-BPA Study.Environmental health perspectives · 2020Article
- Endocrine Disruptors in Water and Their Effects on the Reproductive System.International journal of molecular sciences · 2020Review
- Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Uterine epithelial proliferation is regulated in a paracrine manner by a complex interplay between estrogen (E) and progesterone (P) signaling, in which E stimulates proliferation and P inhibits it. Perturbation of steroid hormone signaling within the uterine milieu could contribute to the development of endometrial hyperplasia and cancer. It is well established that bisphenol-A (BPA) is an endocrine-disrupting chemical with weak estrogenic effects, although little is known about how it affects steroid hormone signaling in the adult uterus. Because BPA acts as a weak E, we hypothesized that chronic exposure to BPA would create an imbalance between E and P signaling and cause changes in the uterus, such as aberrant epithelial proliferation. Indeed, exposure to an environmentally relevant dose of BPA had a uterotrophic affect. BPA-treated mice showed increased proliferation, notably in the glandular epithelium, which are sites of origin for endometrial hyperplasia and cancer. Increased proliferation appeared to be mediated through a similar mechanism as E-induced proliferation, via activation of the fibroblast growth factor receptor pathway and phosphorylation of the ERK1/2 mitogen-activated protein kinases in the epithelium. Interestingly, BPA reduced expression of heart and neural crest derivatives expressed 2 (HAND2), a known mediator of the antiproliferative effects of P. BPA also increased methylation of a CpG island in the Hand2 gene promoter, suggesting that BPA may promote epithelial proliferation through epigenetic silencing of antiproliferative factors like HAND2. Collectively, these findings establish that chronic exposure to BPA impairs steroid hormone signaling in the mouse uterus, and may contribute to the pathogenesis of uterine hyperplasia and cancer.
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Registered trials
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.