Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland
| Autor: | Ana M. Soto, Michael D. Borrero, Nicolas J. Cabaton, Toshi Shioda, Beverly S. Rubin, Carlos Sonnenschein, Perinaaz R. Wadia |
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| Přispěvatelé: | Tufts University School of Medicine, Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Massachusetts General Hospital, Massachusetts General Hospital [Boston] |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Anatomy and Physiology
Mouse Transcription Genetic [SDV]Life Sciences [q-bio] Mammary gland Estrogen receptor Apoptosis Ethinyl Estradiol Epithelium Transcriptomes Mesoderm Mice 0302 clinical medicine Pregnancy Morphogenesis Cluster Analysis 0303 health sciences Principal Component Analysis Multidisciplinary Cancer Risk Factors Environmental Causes of Cancer Gene Expression Regulation Developmental Genomics Animal Models medicine.anatomical_structure Endocrine disruptor Oncology Adipogenesis 030220 oncology & carcinogenesis Prenatal Exposure Delayed Effects Medicine Female GPER hormones hormone substitutes and hormone antagonists Research Article Signal Transduction medicine.medical_specialty endocrine system Science Endocrine System Biology 03 medical and health sciences Model Organisms Fetus Mammary Glands Animal Stroma Phenols Genome Analysis Tools Internal medicine medicine Reproductive Endocrinology Animals RNA Messenger Benzhydryl Compounds 030304 developmental biology Focal Adhesions Endocrine Physiology urogenital system Gene Expression Profiling Estrogen Receptor alpha Computational Biology Hormones Mice Inbred C57BL Endocrinology Endocrine-Related Substances Stromal Cells Transcriptome Troponin C Estrogen receptor alpha Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2013, 8 (5), pp.e63902. ⟨10.1371/journal.pone.0063902⟩ Plos One 5 (8), e63902. (2013) PLoS ONE, Vol 8, Iss 5, p e63902 (2013) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0063902⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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