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  1. Article: The Case for BPA as an Obesogen: Contributors to the Controversy.

    Rubin, Beverly S / Schaeberle, Cheryl M / Soto, Ana M

    Frontiers in endocrinology

    2019  Volume 10, Page(s) 30

    Abstract: Since the inception of the term endocrine disruptor, the idea that the environment is an important determinant of phenotype has motivated researchers to explore the effect of low dose exposure to BPA during organogenesis. The syndrome observed was ... ...

    Abstract Since the inception of the term endocrine disruptor, the idea that the environment is an important determinant of phenotype has motivated researchers to explore the effect of low dose exposure to BPA during organogenesis. The syndrome observed was complex, affecting various endpoints such as reproduction and reproductive tissues, behavior, mammary gland development and carcinogenesis, glucose homeostasis, and obesity. This constellation of impacted endpoints suggests the possibility of complex interactions among the multiple effects of early BPA exposure. One key finding of our rodent studies was alterations of energy and amino-acid metabolism that were detected soon after birth and continued to be present at all time points examined through 6 months of age. The classical manifestations of obesity and associated elements of metabolic disease took a longer time to become apparent. Here we examine the validity of the often-mentioned lack of reproducibility of obesogenic effects of BPA, starting from the known environmental causes of variation, which are diverse and range from the theoretical like the individuation process and the non-monotonicity of the dose-response curve, to the very pragmatic like housing, feed, and time and route of exposure. We then explore environmental conditions that may hinder reproducibility and discuss the effect of confounding factors such as BPA-induced hyperactivity. In spite of all the potential sources of variation, we find that some obesogenic or metabolic effects of BPA are reproducibly observed when study conditions are analogous. We recommend that study authors describe details of their study conditions including the environment, husbandry, and feed. Finally, we show that when experimental conditions are strictly maintained, reproducibility, and stability of the obese phenotype is consistently observed.
    Language English
    Publishing date 2019-02-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2019.00030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects.

    Rubin, Beverly S

    The Journal of steroid biochemistry and molecular biology

    2011  Volume 127, Issue 1-2, Page(s) 27–34

    Abstract: Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. This compound is a building block of polycarbonate plastics often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and ... ...

    Abstract Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. This compound is a building block of polycarbonate plastics often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and beverage containers. Studies have shown that BPA can leach from these and other products in contact with food and drink, and as a result, routine ingestion of BPA is presumed. This compound is also found in an enormous number of other products that we come into contact with daily, and therefore it is not surprising that it has been detected in the majority of individuals examined. BPA is a known endocrine disruptor. Although initially considered to be a weak environmental estrogen, more recent studies have demonstrated that BPA may be similar in potency to estradiol in stimulating some cellular responses. Moreover, emerging evidence suggests that BPA may influence multiple endocrine-related pathways. Studies in rodents have identified adverse effects of BPA at levels at or below the current acceptable daily intake level for this compound. The various reported adverse effects of BPA are reviewed, and potential mechanisms of BPA action are discussed. Much more investigation is needed to understand the potential adverse health effects of BPA exposure in humans and to understand the multiple pathways through which it may act. Although many questions remain to be answered, it is becoming increasingly apparent that exposure to BPA is ubiquitous and that the effects of this endocrine disruptor are complex and wide-ranging.
    MeSH term(s) Animals ; Benzhydryl Compounds ; Endocrine Disruptors/adverse effects ; Endocrine Disruptors/blood ; Environmental Exposure ; Epigenomics ; Female ; Fertility/drug effects ; Humans ; Infant, Newborn ; Mice ; Obesity/chemically induced ; Phenols/adverse effects ; Phenols/blood ; Pregnancy ; Primates ; Rats ; Receptors, Estrogen/agonists ; Receptors, Glucocorticoid/agonists ; Receptors, Thyroid Hormone/antagonists & inhibitors
    Chemical Substances Benzhydryl Compounds ; Endocrine Disruptors ; Phenols ; Receptors, Estrogen ; Receptors, Glucocorticoid ; Receptors, Thyroid Hormone ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2011-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1049188-0
    ISSN 1879-1220 ; 0960-0760
    ISSN (online) 1879-1220
    ISSN 0960-0760
    DOI 10.1016/j.jsbmb.2011.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Perinatal BPA exposure and reproductive axis function in CD-1 mice.

    Acevedo, Nicole / Rubin, Beverly S / Schaeberle, Cheryl M / Soto, Ana M

    Reproductive toxicology (Elmsford, N.Y.)

    2018  Volume 79, Page(s) 39–46

    Abstract: Perinatal Bisphenol-A (BPA) exposure reduces fertility and fecundity in mice. This study examined effects of early BPA exposure on activation of gonadotropin releasing hormone (GnRH) neurons in conjunction with a steroid-induced luteinizing hormone (LH) ... ...

    Abstract Perinatal Bisphenol-A (BPA) exposure reduces fertility and fecundity in mice. This study examined effects of early BPA exposure on activation of gonadotropin releasing hormone (GnRH) neurons in conjunction with a steroid-induced luteinizing hormone (LH) surge, characterized patterns of estrous cyclicity and fertility over time, and assessed the ovarian follicular reserve to further explore factors responsible for the reduced fertility we previously described in this model. The percent activated GnRH neurons was reduced in BPA-exposed females at 3-6 months, and periods of persistent proestrus were increased. These data suggest that perinatal exposure to BPA reduces GnRH neuronal activation required for the generation of the LH surge and estrous cyclicity. Assessments of anti-Müllerian hormone (AMH) levels failed to suggest a decline in the follicular reserve at the BPA exposure levels examined.
    MeSH term(s) Animals ; Anti-Mullerian Hormone/blood ; Benzhydryl Compounds/toxicity ; Endocrine Disruptors/toxicity ; Estrogens/toxicity ; Estrous Cycle/drug effects ; Female ; Fertility/drug effects ; Gonadotropin-Releasing Hormone/metabolism ; Luteinizing Hormone/blood ; Male ; Maternal-Fetal Exchange ; Mice ; Neurons/drug effects ; Neurons/metabolism ; Phenols/toxicity ; Pregnancy
    Chemical Substances Benzhydryl Compounds ; Endocrine Disruptors ; Estrogens ; Phenols ; Gonadotropin-Releasing Hormone (33515-09-2) ; Anti-Mullerian Hormone (80497-65-0) ; Luteinizing Hormone (9002-67-9) ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2018-05-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639342-1
    ISSN 1873-1708 ; 0890-6238
    ISSN (online) 1873-1708
    ISSN 0890-6238
    DOI 10.1016/j.reprotox.2018.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects

    Rubin, Beverly S

    Journal of steroid biochemistry and molecular biology. 2011 Oct., v. 127, no. 1-2

    2011  

    Abstract: Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. This compound is a building block of polycarbonate plastics often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and ... ...

    Abstract Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. This compound is a building block of polycarbonate plastics often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and beverage containers. Studies have shown that BPA can leach from these and other products in contact with food and drink, and as a result, routine ingestion of BPA is presumed. This compound is also found in an enormous number of other products that we come into contact with daily, and therefore it is not surprising that it has been detected in the majority of individuals examined. BPA is a known endocrine disruptor. Although initially considered to be a weak environmental estrogen, more recent studies have demonstrated that BPA may be similar in potency to estradiol in stimulating some cellular responses. Moreover, emerging evidence suggests that BPA may influence multiple endocrine-related pathways. Studies in rodents have identified adverse effects of BPA at levels at or below the current acceptable daily intake level for this compound. The various reported adverse effects of BPA are reviewed, and potential mechanisms of BPA action are discussed. Much more investigation is needed to understand the potential adverse health effects of BPA exposure in humans and to understand the multiple pathways through which it may act. Although many questions remain to be answered, it is becoming increasingly apparent that exposure to BPA is ubiquitous and that the effects of this endocrine disruptor are complex and wide-ranging.
    Keywords acceptable daily intake ; adverse effects ; beverages ; bisphenol A ; containers ; endocrine-disrupting chemicals ; epoxides ; estradiol ; humans ; ingestion ; plastics ; resins ; rodents
    Language English
    Dates of publication 2011-10
    Size p. 27-34.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1049188-0
    ISSN 1879-1220 ; 0960-0760
    ISSN (online) 1879-1220
    ISSN 0960-0760
    DOI 10.1016/j.jsbmb.2011.05.002
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Bisphenol A: Perinatal exposure and body weight.

    Rubin, Beverly S / Soto, Ana M

    Molecular and cellular endocrinology

    2009  Volume 304, Issue 1-2, Page(s) 55–62

    Abstract: Bisphenol A (BPA) is a component of polycarbonate and other plastics including resins that line food and beverage containers. BPA is known to leach from products in contact with food and drink, and is therefore thought to be routinely ingested. In a ... ...

    Abstract Bisphenol A (BPA) is a component of polycarbonate and other plastics including resins that line food and beverage containers. BPA is known to leach from products in contact with food and drink, and is therefore thought to be routinely ingested. In a recent cross sectional study, BPA was detected in urine samples from 92.6% of the US population examined. The potential for BPA to influence body weight is suggested by in vitro studies demonstrating effects of BPA on adipocyte differentiation, lipid accumulation, glucose transport and adiponectin secretion. Data from in vivo studies have revealed dose-dependent and sex dependent effects on body weight in rodents exposed perinatally to BPA. The mechanisms through which perinatal BPA exposure acts to exert persistent effects on body weight and adiposity remain to be determined. Possible targets of BPA action are discussed.
    MeSH term(s) Adipocytes/drug effects ; Animals ; Benzhydryl Compounds ; Body Weight/drug effects ; Diethylstilbestrol/chemistry ; Endocrine Disruptors/chemistry ; Endocrine Disruptors/pharmacology ; Estradiol/chemistry ; Estradiol/metabolism ; Estrogens, Non-Steroidal/chemistry ; Female ; Glucose/metabolism ; Humans ; Male ; Maternal Exposure ; Molecular Structure ; Peroxisome Proliferator-Activated Receptors/metabolism ; Phenols/chemistry ; Phenols/pharmacology ; Pregnancy ; Prenatal Exposure Delayed Effects ; Receptors, Estrogen/metabolism ; Thyroid Hormones/metabolism
    Chemical Substances Benzhydryl Compounds ; ESRRG protein, human ; Endocrine Disruptors ; Estrogens, Non-Steroidal ; Peroxisome Proliferator-Activated Receptors ; Phenols ; Receptors, Estrogen ; Thyroid Hormones ; Estradiol (4TI98Z838E) ; Diethylstilbestrol (731DCA35BT) ; Glucose (IY9XDZ35W2) ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2009-03-09
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2009.02.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Interpreting endocrine disruption from an integrative biology perspective.

    Soto, Ana M / Rubin, Beverly S / Sonnenschein, Carlos

    Molecular and cellular endocrinology

    2009  Volume 304, Issue 1-2, Page(s) 3–7

    Abstract: The ability of reductionism to advance our understanding of complex biological phenomena is limited. The ecological developmental biology (eco-devo) movement rejects the notion that development is merely the unfolding of a genetic program. Fetal exposure ...

    Abstract The ability of reductionism to advance our understanding of complex biological phenomena is limited. The ecological developmental biology (eco-devo) movement rejects the notion that development is merely the unfolding of a genetic program. Fetal exposure to environmental endocrine disruptors may contribute to the increased incidence of male genital tract malformations, decreased sperm quality, several neoplasms, and altered body weight. Here we discuss problems hindering the study of endocrine disruption (reductionist stance, technically driven research biases, and study of single end points, chemicals and exposure periods). We propose the study of both upward and downward causation and a Systems Biology approach to develop quantitative mathematical models for use in computer simulations that would generate testable predictions. This integrative approach will allow the simultaneous consideration of organismal (systemic) effects and effects on various organ systems. It will promote the identification of similar and unique effects of different endocrine disruptors, and their inter-relationships.
    MeSH term(s) Animals ; Endocrine Disruptors/pharmacology ; Environmental Exposure ; Fetus/drug effects ; Humans ; Mutation ; Neoplasms/etiology ; Neoplasms/physiopathology ; Systems Biology
    Chemical Substances Endocrine Disruptors
    Language English
    Publishing date 2009-03-09
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2009.02.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: The addition of peripubertal exposure exacerbates adverse effects in female mice.

    Rubin, Beverly S / Paranjpe, Maneesha / DaFonte, Tracey / Schaeberle, Cheryl / Soto, Ana M / Obin, Martin / Greenberg, Andrew S

    Reproductive toxicology (Elmsford, N.Y.)

    2016  Volume 68, Page(s) 130–144

    Abstract: Body weight (BW) and body composition were examined in CD-1 mice exposed perinatally or perinatally and peripubertally to 0, 0.25, 2.5, 25, or 250μg BPA/kg BW/day. Our goal was to identify the BPA dose (s) and the exposure window(s) that increased BW and ...

    Abstract Body weight (BW) and body composition were examined in CD-1 mice exposed perinatally or perinatally and peripubertally to 0, 0.25, 2.5, 25, or 250μg BPA/kg BW/day. Our goal was to identify the BPA dose (s) and the exposure window(s) that increased BW and adiposity, and to assess potential sex differences in this response. Both perinatal exposure alone and perinatal plus peripubertal exposure to environmentally relevant levels of BPA resulted in lasting effects on body weight and body composition. The effects were dose specific and sex specific and were influenced by the precise window of BPA exposure. The addition of peripubertal BPA exposure following the initial perinatal exposure exacerbated adverse effects in the females but appeared to reduce differences in body weight and body composition between control and BPA exposed males. Some effects of BPA on body weight and body composition showed a non-linear dose response.
    MeSH term(s) Aging/drug effects ; Aging/metabolism ; Animals ; Benzhydryl Compounds/blood ; Benzhydryl Compounds/toxicity ; Body Composition/drug effects ; Body Weight/drug effects ; Dose-Response Relationship, Drug ; Environmental Pollutants/blood ; Environmental Pollutants/toxicity ; Female ; Male ; Mice ; Phenols/blood ; Phenols/toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Prenatal Exposure Delayed Effects/metabolism ; Sex Factors
    Chemical Substances Benzhydryl Compounds ; Environmental Pollutants ; Phenols ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2016-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639342-1
    ISSN 1873-1708 ; 0890-6238
    ISSN (online) 1873-1708
    ISSN 0890-6238
    DOI 10.1016/j.reprotox.2016.07.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The male mammary gland: a target for the xenoestrogen bisphenol A.

    Vandenberg, Laura N / Schaeberle, Cheryl M / Rubin, Beverly S / Sonnenschein, Carlos / Soto, Ana M

    Reproductive toxicology (Elmsford, N.Y.)

    2013  Volume 37, Page(s) 15–23

    Abstract: Males of some strains of mice retain their mammary epithelium even in the absence of nipples. Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections. We also examined the effects of bisphenol A (BPA) ...

    Abstract Males of some strains of mice retain their mammary epithelium even in the absence of nipples. Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections. We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland. BPA was administered at a range of environmentally relevant doses (0.25-250μg/kg/day) to pregnant and lactating mice and then the mammary glands of male offspring were examined at several periods in adulthood. We observed age- and dose-specific effects on mammary gland morphology, indicating that perinatal BPA exposures alter the male mammary gland in adulthood. These results may provide insight into gynecomastia, the most common male breast disease in humans, where proliferation of the mammary epithelium leads to breast enlargement.
    MeSH term(s) Age Factors ; Animals ; Benzhydryl Compounds/toxicity ; Dose-Response Relationship, Drug ; Epithelium/anatomy & histology ; Epithelium/drug effects ; Estrogens/toxicity ; Female ; Male ; Mammary Glands, Animal/anatomy & histology ; Mammary Glands, Animal/drug effects ; Mice ; Phenols/toxicity ; Pregnancy
    Chemical Substances Benzhydryl Compounds ; Estrogens ; Phenols ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2013-01-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639342-1
    ISSN 1873-1708 ; 0890-6238
    ISSN (online) 1873-1708
    ISSN 0890-6238
    DOI 10.1016/j.reprotox.2013.01.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Anterior pituitary gene expression with reproductive aging in the female rat.

    Zheng, Weiming / Jimenez-Linan, Mercedes / Rubin, Beverly S / Halvorson, Lisa M

    Biology of reproduction

    2007  Volume 76, Issue 6, Page(s) 1091–1102

    Abstract: Although reproductive aging in women is classically attributed to loss of ovarian follicles, recent data have suggested that the entire hypothalamic-pituitary-ovarian axis undergoes functional changes with time. The aim of this study was to characterize ... ...

    Abstract Although reproductive aging in women is classically attributed to loss of ovarian follicles, recent data have suggested that the entire hypothalamic-pituitary-ovarian axis undergoes functional changes with time. The aim of this study was to characterize age-related changes in pituitary gene expression for factors with known importance for gonadotroph function, including 1) steroid hormone receptors (Esr and Pgr), 2) orphan nuclear receptors [Nr5a1 (steroidogenic factor-1) and Nr5a2 (liver receptor homologue-1)], and 3) pituitary-derived polypeptides (activin, inhibin, and follistatin), as well as 4) gonadotropin subunits and 5) GnRH receptors. We chose to utilize a middle-aged rat model for these studies. Young (Y; 3-mo-old) and middle-aged (MA; 9- to 12-mo-old) rats were ovariectomized, primed with estradiol, and injected with progesterone to induce an LH surge. The mRNA levels for the gonadotropin subunits and GnRH receptors were decreased in middle-aged females relative to young animals. Nr5a1 and follistatin mRNA levels were significantly greater in Y versus MA animals following ovariectomy. Furthermore, steroid-induced regulation of these genes was lost in the MA animals. Regulation of the Nr5a2, Inhba, and Inhbb transcripts was also limited to the young animals. In contrast, there were no significant differences in the mRNA levels of Esr or Pgr family members between age groups at any time point. Although this in vivo model normalizes ovarian steroid levels, it does not control for potential differences in GnRH stimulation with aging. Therefore, in a second set of experiments, we used an in vitro perifusion system to compare the effects of pulsatile GnRH in the two age groups. Nr5a1 mRNA expression was greater in Y than MA animals and was significantly decreased by GnRH pulses in both age groups. Follistatin mRNA levels increased significantly with GnRH treatment in Y animals but were not significantly changed in the MA females. Taken together, these data demonstrate gene-specific blunting of pituitary gene expression postovariectomy and during the steroid-induced surge in middle-aged rats. We propose that age-related changes in pituitary physiology may contribute to reproductive senescence.
    MeSH term(s) Aging/genetics ; Animals ; Female ; Follistatin/genetics ; Follistatin/metabolism ; Gene Expression/drug effects ; Gonadotropin-Releasing Hormone/genetics ; Gonadotropin-Releasing Hormone/metabolism ; Gonadotropin-Releasing Hormone/pharmacology ; Gonadotropins, Pituitary/genetics ; Gonadotropins, Pituitary/metabolism ; Inhibins/genetics ; Inhibins/metabolism ; Luteinizing Hormone/blood ; Ovariectomy ; Pituitary Gland, Anterior/metabolism ; Protein Subunits/genetics ; Protein Subunits/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/genetics ; Receptors, Progesterone/metabolism ; Reproduction/genetics ; Steroidogenic Factor 1
    Chemical Substances Follistatin ; Gonadotropins, Pituitary ; NR5A2 protein, rat ; Protein Subunits ; RNA, Messenger ; Receptors, Cytoplasmic and Nuclear ; Receptors, Estrogen ; Receptors, Progesterone ; Steroidogenic Factor 1 ; steroidogenic factor 1, rat ; Gonadotropin-Releasing Hormone (33515-09-2) ; Inhibins (57285-09-3) ; Luteinizing Hormone (9002-67-9)
    Language English
    Publishing date 2007-06
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1118-6
    ISSN 1529-7268 ; 0006-3363
    ISSN (online) 1529-7268
    ISSN 0006-3363
    DOI 10.1095/biolreprod.106.057877
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland.

    Wadia, Perinaaz R / Cabaton, Nicolas J / Borrero, Michael D / Rubin, Beverly S / Sonnenschein, Carlos / Shioda, Toshi / Soto, Ana M

    PloS one

    2013  Volume 8, Issue 5, Page(s) e63902

    Abstract: Exposure of rodent fetuses to low doses of the endocrine disruptor bisphenol A (BPA) causes subtle morphological changes in the prenatal mammary gland and results in pre-cancerous and cancerous lesions during adulthood. To examine whether the BPA-induced ...

    Abstract Exposure of rodent fetuses to low doses of the endocrine disruptor bisphenol A (BPA) causes subtle morphological changes in the prenatal mammary gland and results in pre-cancerous and cancerous lesions during adulthood. To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a) associated with changes in mRNA expression reflecting estrogenic actions and/or b) dependent on the estrogen receptor α (ERα), we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2) on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E) 8 were harvested at E19. Transcriptomal analyses on the ductal epithelium and periductal stroma revealed altered expression of genes involved in the focal adhesion and adipogenesis pathways in the BPA-exposed stroma while genes regulating the apoptosis pathway changed their expression in the BPA-exposed epithelium. These changes in gene expression correlated with previously reported histological changes in matrix organization, adipogenesis, and lumen formation resulting in enhanced maturation of the fat-pad and delayed lumen formation in the epithelium of BPA-exposed fetal mammary glands. Overall similarities in the transcriptomal effects of BPA and EE2 were more pronounced in the epithelium, than in the stroma. In addition, the effects of BPA and EE2 on the expression of various genes involved in mammary stromal-epithelial interactions were suppressed in the absence of ERα. These observations support a model whereby BPA and EE2 act directly on the stroma, which expresses ERα, ERβ and GPR30 in fetal mammary glands, and that the stroma, in turn, affects gene expression in the epithelium, where ERα and ERβ are below the level of detection at this stage of development.
    MeSH term(s) Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Benzhydryl Compounds/toxicity ; Cluster Analysis ; Epithelium/drug effects ; Epithelium/metabolism ; Estrogen Receptor alpha/metabolism ; Ethinyl Estradiol/pharmacology ; Female ; Fetus/drug effects ; Fetus/metabolism ; Focal Adhesions/drug effects ; Focal Adhesions/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/drug effects ; Mammary Glands, Animal/drug effects ; Mammary Glands, Animal/embryology ; Mammary Glands, Animal/metabolism ; Mammary Glands, Animal/pathology ; Mesoderm/drug effects ; Mesoderm/metabolism ; Mice ; Mice, Inbred C57BL ; Phenols/toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects/genetics ; Prenatal Exposure Delayed Effects/pathology ; Principal Component Analysis ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Stromal Cells/drug effects ; Stromal Cells/metabolism ; Transcription, Genetic/drug effects ; Transcriptome/genetics ; Troponin C/metabolism
    Chemical Substances Benzhydryl Compounds ; Estrogen Receptor alpha ; Phenols ; RNA, Messenger ; Troponin C ; Ethinyl Estradiol (423D2T571U) ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2013-05-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0063902
    Database MEDical Literature Analysis and Retrieval System OnLINE

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