ArticlePloS one2015
Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 77 citations in OpenAlex.
- Organoid-based systems for biomedical innovation: advances in disease modeling, drug screening, and precision medicine.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Bisphenol A and prostate cancer: from population exposure to context-dependent mechanisms and translational implications.Frontiers in cell and developmental biology · 2026Review
- Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review).International journal of molecular medicine · 2025Review
- Prostatic lineage differentiation from human embryonic stem cells through inducible expression of NKX3-1.Stem cell research & therapy · 2024Article
- Advances in the application of colorectal cancer organoids in precision medicine.Frontiers in oncology · 2024Review
- Engineering prostate cancer in vitro: what does it take?Oncogene · 2023Review
- Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs.EFSA journal. European Food Safety Authority · 2023Article
- Single-Cell and Spatial Analysis of Emergent Organoid Platforms.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Individual and Combined Effect of Bisphenol A and Bisphenol AF on Prostate Cell Proliferation through NF-κB Signaling Pathway.International journal of molecular sciences · 2022Article
- Prostate organogenesis.Development (Cambridge, England) · 2022Article
- Per- and polyfluoroalkyl substances target and alter human prostate stem-progenitor cells.Biochemical pharmacology · 2022Article
- Combined Effects of Different Endocrine-Disrupting Chemicals (EDCs) on Prostate Gland.International journal of environmental research and public health · 2021Review
- The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update.International journal of molecular sciences · 2021Review
- Breast and prostate glands affected by environmental substances (Review).Oncology reports · 2021Review
- Organoid culture to study epithelial cell differentiation and barrier formation in the colon: bridging the gap between monolayer cell culture and human subject research.In vitro cellular & developmental biology. Animal · 2021Review
- Chemically Defined Conditions Mediate an Efficient Induction of Dental Pulp Pluripotent-Like Stem Cells into Hepatocyte-Like Cells.Stem cells international · 2021Article
- Application of Organoid Models in Prostate Cancer Research.Frontiers in oncology · 2021Review
- Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation.Frontiers in cell and developmental biology · 2021Review
- Human Embryos, Induced Pluripotent Stem Cells, and Organoids: Models to Assess the Effects of Environmental Plastic Pollution.Frontiers in cell and developmental biology · 2021Review
- The use of induced pluripotent stem cells in domestic animals: a narrative review.BMC veterinary research · 2020Review
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2 authors at 1 institution in 1 country.
Funding
Abstract
Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA) can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC) into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.
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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.