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  1. Article ; Online: Developmental estrogenization: Prostate gland reprogramming leads to increased disease risk with aging.

    Prins, Gail S

    Differentiation; research in biological diversity

    2021  Volume 118, Page(s) 72–81

    Abstract: While estrogens are involved in normal prostate morphogenesis and function, inappropriate early-life estrogenic exposures, either in type, dose or timing, can reprogram the prostate gland and lead to increased disease risk with aging. This process is ... ...

    Abstract While estrogens are involved in normal prostate morphogenesis and function, inappropriate early-life estrogenic exposures, either in type, dose or timing, can reprogram the prostate gland and lead to increased disease risk with aging. This process is referred to as estrogen imprinting or developmental estrogenization of the prostate gland. The present review discusses published and new evidence for prostatic developmental estrogenization that includes extensive research in rodent models combined with epidemiology findings that together have helped to uncover the architectural and molecular underpinnings that promote this phenotype. Complex interactions between steroid receptors, developmental morphoregulatory factors, epigenetic machinery and stem-progenitor cell targets coalesce to hard wire structural, cellular and epigenomic reorganization of the tissue which retains a life-long memory of early-life estrogens, ultimately predisposing the gland to prostatitis, hyperplasia and carcinogenesis with aging.
    MeSH term(s) Aging/genetics ; Aging/metabolism ; Aging/pathology ; Animals ; Animals, Newborn ; Carcinogenesis/genetics ; Epigenomics ; Estrogens/genetics ; Estrogens/metabolism ; Gene Expression Regulation, Developmental ; Genomic Imprinting ; Humans ; Hyperplasia/genetics ; Hyperplasia/metabolism ; Hyperplasia/pathology ; Male ; Prostate/metabolism ; Prostate/pathology ; Prostatitis/genetics ; Prostatitis/metabolism ; Prostatitis/pathology ; Receptors, Steroid/genetics ; Stem Cells/metabolism
    Chemical Substances Estrogens ; Receptors, Steroid
    Language English
    Publishing date 2021-01-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 184540-8
    ISSN 1432-0436 ; 0301-4681
    ISSN (online) 1432-0436
    ISSN 0301-4681
    DOI 10.1016/j.diff.2020.12.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1170: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  2. Article ; Online: Evaluating adverse effects of environmental agents in food: a brief critique of the US FDA's criteria.

    Vandenberg, Laura N / Zoeller, R Thomas / Prins, Gail S / Trasande, Leonardo

    Environmental health : a global access science source

    2023  Volume 22, Issue 1, Page(s) 38

    Abstract: Background: In the US, the Food and Drug Administration (US FDA) is charged with protecting the safety of food from both pathogens and chemicals used in food production and food packaging. To protect the public in a transparent manner, the FDA needs to ... ...

    Abstract Background: In the US, the Food and Drug Administration (US FDA) is charged with protecting the safety of food from both pathogens and chemicals used in food production and food packaging. To protect the public in a transparent manner, the FDA needs to have an operational definition of what it considers to be an "adverse effect" so that it can take action against harmful agents. The FDA has recently published two statements where, for the first time, it defines the characteristics of an adverse effect that it uses to interpret toxicity studies.
    Objective: In this brief review, we examine two recent actions by the FDA, a proposed rule regarding a color additive used in vegetarian burgers and a decision not to recall fish with high levels of scombrotoxin. We evaluated the FDA's description of the criteria used to determine which outcomes should be considered adverse.
    Overview: We describe three reasons why the FDA's criteria for "adverse effects" is not public health protective. These include an unscientific requirement for a monotonic dose response, which conflates hazard assessment and dose response assessment while also ignoring evidence for non-linear and non-monotonic effects for many environmental agents; a requirement that the effect be observed in both sexes, which fails to acknowledge the many sex- and gender-specific effects on physiology, disease incidence and severity, and anatomy; and a requirement that the effects are irreversible, which does not acknowledge the role of exposure timing or appreciate transgenerational effects that have been demonstrated for environmental chemicals.
    Conclusions: The FDA's criteria for identifying adverse effects are inadequate because they are not science-based. Addressing this is important, because the acknowledgement of adverse effects is central to regulatory decisions and the protection of public health.
    MeSH term(s) United States ; Food Safety ; United States Food and Drug Administration
    Language English
    Publishing date 2023-04-21
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2092232-2
    ISSN 1476-069X ; 1476-069X
    ISSN (online) 1476-069X
    ISSN 1476-069X
    DOI 10.1186/s12940-023-00971-2
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  3. Article ; Online: The Endocrine Society Centennial: Hormones and Apoptosis in the Prostate Gland… Live and Let Die.

    Prins, Gail S

    Endocrinology

    2016  Volume 157, Issue 6, Page(s) 2197–2200

    Language English
    Publishing date 2016-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/en.2016-1192
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  4. Article ; Online: Expression patterns of sex steroid receptors in developing mesonephros of the male mouse: three-dimensional analysis.

    Omotehara, Takuya / Hess, Rex A / Nakata, Hiroki / Birch, Lynn A / Prins, Gail S / Itoh, Masahiro

    Cell and tissue research

    2023  Volume 393, Issue 3, Page(s) 577–593

    Abstract: The androgen pathway via androgen receptor (AR) has received the most attention for development of male reproductive tracts. The estrogen pathway through estrogen receptor (ESR1) is also a major contributor to rete testis and efferent duct formation, but ...

    Abstract The androgen pathway via androgen receptor (AR) has received the most attention for development of male reproductive tracts. The estrogen pathway through estrogen receptor (ESR1) is also a major contributor to rete testis and efferent duct formation, but the role of progesterone via progesterone receptor (PGR) has largely been overlooked. Expression patterns of these receptors in the mesonephric tubules (MTs) and Wolffian duct (WD), which differentiate into the efferent ductules and epididymis, respectively, remain unclear because of the difficulty in distinguishing each region of the tracts. This study investigated AR, ESR1, and PGR expressions in the murine mesonephros using three-dimensional (3-D) reconstruction. The receptors were localized in serial paraffin sections of the mouse testis and mesonephros by immunohistochemistry on embryonic days (E) 12.5, 15.5, and 18.5. Specific regions of the developing MTs and WD were determined by 3-D reconstruction using Amira software. AR was found first in the specific portion of the MTs near the MT-rete junction at E12.5, and the epithelial expression showed increasing strength from cranial to the caudal regions. Epithelial expression of ESR1 was found in the cranial WD and MTs near the WD first at E15.5. PGR was weakly positive only in the MTs and cranial WD starting on E15.5. This 3-D analysis suggests that gonadal androgen acts first on the MTs near the MT-rete junction but that estrogen is the first to influence MTs near the WD, while potential PGR activity is delayed and limited to the epithelium.
    MeSH term(s) Male ; Animals ; Mice ; Mesonephros ; Androgens ; Epididymis ; Receptors, Estrogen ; Receptors, Androgen ; Gonadal Steroid Hormones ; Estrogens
    Chemical Substances Androgens ; Receptors, Estrogen ; Receptors, Androgen ; Gonadal Steroid Hormones ; Estrogens
    Language English
    Publishing date 2023-06-19
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 125067-x
    ISSN 1432-0878 ; 0302-766X
    ISSN (online) 1432-0878
    ISSN 0302-766X
    DOI 10.1007/s00441-023-03796-0
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  5. Article ; Online: Development priority.

    Grandjean, Philippe / Prins, Gail S / Weihe, Pal

    Basic & clinical pharmacology & toxicology

    2019  Volume 125 Suppl 3, Page(s) 3–4

    MeSH term(s) Benzhydryl Compounds/adverse effects ; Congresses as Topic ; Embryonic Development/drug effects ; Endocrine Disruptors/adverse effects ; Environmental Exposure/adverse effects ; Environmental Pollutants/adverse effects ; Female ; Fetal Development/drug effects ; Humans ; Phenols/adverse effects ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Prenatal Exposure Delayed Effects/prevention & control
    Chemical Substances Benzhydryl Compounds ; Endocrine Disruptors ; Environmental Pollutants ; Phenols ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2019-06-28
    Publishing country England
    Document type Editorial
    ZDB-ID 2134679-3
    ISSN 1742-7843 ; 1742-7835
    ISSN (online) 1742-7843
    ISSN 1742-7835
    DOI 10.1111/bcpt.13249
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  6. Article: Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer.

    Boyd, Raya I / Ahmad, Saeed / Singh, Ratnakar / Fazal, Zeeshan / Prins, Gail S / Madak Erdogan, Zeynep / Irudayaraj, Joseph / Spinella, Michael J

    Cancers

    2022  Volume 14, Issue 12

    Abstract: Poly- and perfluoroalkylated substances (PFAS) are chemicals that persist and bioaccumulate in the environment and are found in nearly all human populations through several routes of exposure. Human occupational and community exposure to PFAS has been ... ...

    Abstract Poly- and perfluoroalkylated substances (PFAS) are chemicals that persist and bioaccumulate in the environment and are found in nearly all human populations through several routes of exposure. Human occupational and community exposure to PFAS has been associated with several cancers, including cancers of the kidney, testis, prostate, and liver. While evidence suggests that PFAS are not directly mutagenic, many diverse mechanisms of carcinogenicity have been proposed. In this mini-review, we organize these mechanisms into three major proposed pathways of PFAS action-metabolism, endocrine disruption, and epigenetic perturbation-and discuss how these distinct but interdependent pathways may explain many of the proposed pro-carcinogenic effects of the PFAS class of environmental contaminants. Notably, each of the pathways is predicted to be highly sensitive to the dose and window of exposure which may, in part, explain the variable epidemiologic and experimental evidence linking PFAS and cancer. We highlight testicular and prostate cancer as models to validate this concept.
    Language English
    Publishing date 2022-06-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14122919
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  7. Article ; Online: Morphometric Analysis of Rat Prostate Development: Roles of MEK/ERK and Rho Signaling Pathways in Prostatic Morphogenesis.

    Hu, Wen-Yang / Afradiasbagharani, Parivash / Lu, Ranli / Liu, Lifeng / Birch, Lynn A / Prins, Gail S

    Biomolecules

    2021  Volume 11, Issue 12

    Abstract: The molecular mechanisms underlying prostate development can provide clues for prostate cancer research. It has been demonstrated that MEK/ERK signaling downstream of androgen-targeted FGF10 signaling directly induces prostatic branching during ... ...

    Abstract The molecular mechanisms underlying prostate development can provide clues for prostate cancer research. It has been demonstrated that MEK/ERK signaling downstream of androgen-targeted FGF10 signaling directly induces prostatic branching during development, while Rho/Rho-kinase can regulate prostate cell proliferation. MEK/ERK and Rho/Rho kinase regulate myosin light chain kinase (MLCK), and MLCK regulates myosin light chain phosphorylation (MLC-P), which is critical for cell fate, including cell proliferation, differentiation, and apoptosis. However, the roles and crosstalk of the MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis have not been examined. In the present study, we used numerical and image analysis to characterize lobe-specific rat prostatic branching during postnatal organ culture and investigated the roles of FGF10-MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis. Prostates exhibited distinctive lobe-specific growth and branching patterns in the ventral (VP) and lateral (LP) lobes, while exogenous FGF10 treatment shifted LP branching towards a VP branching pattern. Treatment with inhibitors of MEK1/2, Rho, Rho kinase, or MLCK significantly inhibited VP growth and blocked branching morphogenesis, further supporting critical roles for MEK/ERK and Rho/Rho kinase signaling pathways in prostatic growth and branching during development. We propose that MLCK-regulated MLC-P may be a central downstream target of both signaling pathways in regulating prostate morphogenesis.
    MeSH term(s) Animals ; Cell Differentiation ; Cell Proliferation ; Fibroblast Growth Factor 10/metabolism ; Gene Expression Regulation, Developmental ; MAP Kinase Signaling System ; Male ; Morphogenesis ; Organ Culture Techniques ; Prostate/growth & development ; Prostate/metabolism ; Rats ; rho-Associated Kinases/metabolism
    Chemical Substances Fgf10 protein, rat ; Fibroblast Growth Factor 10 ; rho-Associated Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2021-12-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom11121829
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  8. Article: Stem cells from a malignant rat prostate cell line generate prostate cancers

    Hu, Wen-Yang / Liu, Li-Feng / Afradiasbagharani, Parivash / Lu, Ran-Li / Chen, Zhen-Long / Hu, Dan-Ping / Birch, Lynn A / Prins, Gail S

    American journal of clinical and experimental urology

    2022  Volume 10, Issue 6, Page(s) 377–389

    Abstract: Cancer stem cells (CSCs) are resistant to conventional cancer therapies, permitting the repopulation of new tumor growth and driving disease progression. Models for testing prostate CSC-propagated tumor growth are presently limited yet necessary for ... ...

    Abstract Cancer stem cells (CSCs) are resistant to conventional cancer therapies, permitting the repopulation of new tumor growth and driving disease progression. Models for testing prostate CSC-propagated tumor growth are presently limited yet necessary for therapeutic advancement. Utilizing the congenic nontumorigenic NRP152 and tumorigenic NRP154 rat prostate epithelial cell lines, the present study investigated the self-renewal, differentiation, and regenerative abilities of prostate stem/progenitor cells and developed a CSC-based PCa model. NRP154 cells expressed reduced levels of tumor suppressor caveolin-1 and increased p-Src as compared to NRP152 cells. Gene knockdown of caveolin-1 in NRP152 cells upregulated p-Src, implicating their role as potential oncogenic mediators in NRP154 cells. A FACS-based Hoechst exclusion assay revealed a side population of stem-like cells (0.1%) in both NRP152 and NRP154 cell lines. Using a 3D Matrigel culture system, stem cells from both cell lines established prostaspheres at a 0.1% efficiency through asymmetric self-renewal and rapid proliferation of daughter progenitor cells. Spheres derived from both cell lines contained CD117
    Language English
    Publishing date 2022-12-25
    Publishing country United States
    Document type Journal Article
    ISSN 2330-1910
    ISSN 2330-1910
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: WNT2 is necessary for normal prostate gland cyto-differentiation and modulates prostate growth in an FGF10 dependent manner.

    Madueke, Ikenna C / Hu, Wen-Yang / Huang, Liwei / Prins, Gail S

    American journal of clinical and experimental urology

    2018  Volume 6, Issue 4, Page(s) 154–163

    Abstract: ... species. This study investigates the role(s) of Wnt2 during prostate gland development. ...

    Abstract Wnt proteins are highly conserved secreted morphogens that function in organ development across species. This study investigates the role(s) of Wnt2 during prostate gland development.
    Language English
    Publishing date 2018-08-20
    Publishing country United States
    Document type Journal Article
    ISSN 2330-1910
    ISSN 2330-1910
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  10. Article ; Online: Keratin Profiling by Single-Cell RNA-Sequencing Identifies Human Prostate Stem Cell Lineage Hierarchy and Cancer Stem-Like Cells.

    Hu, Wen-Yang / Hu, Dan-Ping / Xie, Lishi / Nonn, Larisa / Lu, Ranli / Abern, Michael / Shioda, Toshihiro / Prins, Gail S

    International journal of molecular sciences

    2021  Volume 22, Issue 15

    Abstract: Single prostate stem cells can generate stem and progenitor cells to form prostaspheres in 3D culture. Using a prostasphere-based label retention assay, we recently identified keratin 13 ( ...

    Abstract Single prostate stem cells can generate stem and progenitor cells to form prostaspheres in 3D culture. Using a prostasphere-based label retention assay, we recently identified keratin 13 (
    MeSH term(s) Adult ; Cells, Cultured ; Humans ; Keratins/metabolism ; Male ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Primary Cell Culture ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; RNA/metabolism ; Single-Cell Analysis ; Young Adult
    Chemical Substances RNA (63231-63-0) ; Keratins (68238-35-7)
    Language English
    Publishing date 2021-07-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22158109
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