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      Neuro-toxic and Reproductive Effects of BPA

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          Abstract

          Background:

          Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. It has recognized activity as an endocrine-disrupting chemical and has suspected roles as a neurological and reproductive toxicant. It interferes in steroid signaling, induces oxidative stress, and affects gene expression epigenetically. Gestational, perinatal and neonatal exposures to BPA affect developmental processes, including brain development and gametogenesis, with consequences on brain functions, behavior, and fertility.

          Methods:

          This review critically analyzes recent findings on the neuro-toxic and reproductive effects of BPA (and its ana-logues), with focus on neuronal differentiation, synaptic plasticity, glia and microglia activity, cognitive functions, and the central and local control of reproduction.

          Results:

          BPA has potential human health hazard associated with gestational, peri- and neonatal exposure. Beginning with BPA’s disposition, this review summarizes recent findings on the neurotoxicity of BPA and its analogues, on neuronal dif-ferentiation, synaptic plasticity, neuro-inflammation, neuro-degeneration, and impairment of cognitive abilities. Furthermore, it reports the recent findings on the activity of BPA along the HPG axis, effects on the hypothalamic Gonadotropin Releas-ing Hormone (GnRH), and the associated effects on reproduction in both sexes and successful pregnancy.

          Conclusion:

          BPA and its analogues impair neuronal activity, HPG axis function, reproduction, and fertility. Contrasting re-sults have emerged in animal models and human. Thus, further studies are needed to better define their safety levels. This re-view offers new insights on these issues with the aim to find the “fil rouge”, if any, that characterize BPA’s mechanism of action with outcomes on neuronal function and reproduction.

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          Most cited references223

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          Mechanisms and functional implications of adult neurogenesis.

          The generation of new neurons is sustained throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. In this review, we discuss the factors that regulate proliferation and fate determination of adult neural stem cells and describe recent studies concerning the integration of newborn neurons into the existing neural circuitry. We further address the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
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            Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004

            Background Bisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States. Objectives We aimed to assess exposure to BPA and tOP in the U.S. general population. Methods We measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants ≥ 6 years of age in the 2003–2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry. Results BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p $45,000/year). Conclusions Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.
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              Milestones of neuronal development in the adult hippocampus.

              Adult hippocampal neurogenesis originates from precursor cells in the adult dentate gyrus and results in new granule cell neurons. We propose a model of the development that takes place between these two fixed points and identify several developmental milestones. From a presumably bipotent radial-glia-like stem cell (type-1 cell) with astrocytic properties, development progresses over at least two stages of amplifying lineage-determined progenitor cells (type-2 and type-3 cells) to early postmitotic and to mature neurons. The selection process, during which new neurons are recruited into function, and other regulatory influences differentially affect the different stages of development.
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                Author and article information

                Journal
                Curr Neuropharmacol
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers
                1570-159X
                1875-6190
                December 2019
                December 2019
                : 17
                : 12
                : 1109-1132
                Affiliations
                Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, 
SA, Italy;

                Department of Experimental Medicine, University of Campania “Luigi Vanvitelli” , Caserta, , Italy;

                Theoreo srl – Spin-off company of the University of Salerno, Salerno, , Italy;

                European Biomedical Research Institute of Salerno (EBRIS), Salerno, , Italy;

                University of Tennessee College of Medicine, Department of Obstetrics and Gynecology , 
Chattanooga, , TN , USA;

                Department of Biology, Geology and Environmental Sciences, University of Tennessee at Chattanooga , Chattanooga, , TN , USA;

                Department of Movement Sciences and Wellbeing, Parthenope University of Naples , Naples, , Italy
                Author notes
                [* ]Address correspondence to this author at the Department of Movement Sciences and Wellbeing, University of Naples “Parthenope”, Via Medina 40, 80133 Napoli, Italy; Tel: +39 081 5474668; Fax: +39 081 5474678;, E-mail: rosaria.meccariello@ 123456uniparthenope.it
                Article
                CN-17-1109
                10.2174/1570159X17666190726112101
                7057208
                31362658
                5ec55181-2344-4b12-a65a-9213d55ad45f
                © 2019 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 30 April 2019
                : 04 June 2019
                : 19 July 2019
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                bpa,neuronal differentiation,synaptic plasticity,neuroinflammation,epigenetics,hypothalamus,hpg axis,gnrh,kiss1,reproduction

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