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Contents tagged “mammary glands”

There are 4 contents with the tag “mammary glands”:

  1. A combined morphometric and statistical approach to assess non-monotonicity in the developing mammary gland of rats in the CLARITY-BPA study

    A combined morphometric and statistical approach to assess non-monotonicity in the developing mammary gland of rats in the CLARITY-BPA study

    Environmental Health Perspectives


    We can and should take advantage of nonmonotonic properties to perform statistical analysis rigorously by new statistical and morphometric methods.

    Manuscript Supplementary Citation Publisher Full text

    Abstract:

    We aimed to a) determine whether BPA showed effects on the developing rat mammary gland using new quantitative and established semiquantitative methods in two laboratories, b) develop a software tool for automatic evaluation of quantifiable aspects of the mammary ductal tree, and c) compare those methods. Conclusions: Both the semiquantitative and the quantitative methods revealed nonmonotonic effects of BPA. The quantitative unsupervised analysis used 91 measurements and produced the most striking nonmonotonic dose–response curves. At all time points, lower doses resulted in larger effects, consistent with the core study, which revealed a significant increase of mammary adenocarcinoma incidence in the stop-dose animals at the lowest BPA dose tested.

    Citation:

    Montévil, Maël, Nicole Acevedo, Cheryl M. Schaeberle, Manushree Bharadwaj, Suzanne E. Fenton, and Ana M. Soto. 2020. “A Combined Morphometric and Statistical Approach to Assess Non-Monotonicity in the Developing Mammary Gland of Rats in the CLARITY-BPA Study.” Environmental Health Perspectives 128 (5): 057001. https://doi.org/10.1289/EHP6301

  2. Theoretical approach of ductal morphogenesis

    Theoretical approach of ductal morphogenesis

    Journal of Theoretical and Applied Vascular Research


    We propose a framework to model the behavior of cells in tissues and develop an application in the case of ductal morphogenesis.

    Manuscript Citation Publisher Full text

    Abstract:

    We developed 3D culture methods that reproduce in vitro mammary gland ductal morphogenesis. We are proposing a conceptual framework to understand morphogenetic events based on epistemologically sound biological principles instead of the common practice of using only physical principles. More specifically, our theoretical framework is based on the principle that the default state of cells is proliferation with variation and motility. We emphasize the role played by the agency of cells embedded in a gel and the circularity that is relevant for the intended process, whereby cells act upon other cells and on matrix elements, and are subject to the agentivity of neighboring cells. This circularity strongly differs from classical linear causality. Finally, our approach opens up the study of causal determination to multilevel explanations rather than to reductive ones involving only molecules in general and genes in particular.

    Keywords: Morphogenesis, extracellular matrix, theoretical principles, default state of cells, modelization.

    Citation:

    Montevil, M., Carlos Sonnenschein, and Ana M. Soto. 2016. “Theoretical Approach of Ductal Morphogenesis.” Journal of Theoretical and Applied Vascular Research 1 (1): 45–49. https://doi.org/10.24019/jtavr.7

  3. Modeling mammary organogenesis from biological first principles: Cells and their physical constraints

    Modeling mammary organogenesis from biological first principles: Cells and their physical constraints

    Progress in Biophysics and Molecular Biology


    We developed a mathematical model of mammary gland based on proper biological principles: the default state of cell and the principle of organization.

    Manuscript Citation Publisher Full text

    Abstract:

    Abstract In multicellular organisms, relations among parts and between parts and the whole are contextual and interdependent. These organisms and their cells are ontogenetically linked: an organism starts as a cell that divides producing non-identical cells, which organize in tri-dimensional patterns. These association patterns and cells types change as tissues and organs are formed. This contextuality and circularity makes it difficult to establish detailed cause and effect relationships. Here we propose an approach to overcome these intrinsic difficulties by combining the use of two models; 1) an experimental one that employs 3D culture technology to obtain the structures of the mammary gland, namely, ducts and acini, and 2) a mathematical model based on biological principles. The typical approach for mathematical modeling in biology is to apply mathematical tools and concepts developed originally in physics or computer sciences. Instead, we propose to construct a mathematical model based on proper biological principles. Specifically, we use principles identified as fundamental for the elaboration of a theory of organisms, namely i) the default state of cell proliferation with variation and motility and ii) the principle of organization by closure of constraints. This model has a biological component, the cells, and a physical component, a matrix which contains collagen fibers. Cells display agency and move and proliferate unless constrained; they exert mechanical forces that i) act on collagen fibers and ii) on other cells. As fibers organize, they constrain the cells on their ability to move and to proliferate. The model exhibits a circularity that can be interpreted in terms of closure of constraints. Implementing the mathematical model shows that constraints to the default state are sufficient to explain ductal and acinar formation, and points to a target of future research, namely, to inhibitors of cell proliferation and motility generated by the epithelial cells. The success of this model suggests a step-wise approach whereby additional constraints imposed by the tissue and the organism could be examined in silico and rigorously tested by in vitro and in vivo experiments, in accordance with the organicist perspective we embrace.

    Keywords: Ductal morphogenesis, Mathematical models, Organicism, Organizational closure, Acinar morphogenesis, Mammary gland morphogenesis

    Citation:

    Montévil, Maël, L. Speroni, Carlos Sonnenschein, and Ana M. Soto. 2016. “Modeling Mammary Organogenesis from Biological First Principles: Cells and Their Physical Constraints.” Progress in Biophysics and Molecular Biology 122 (1): 58–69. https://doi.org/10.1016/j.pbiomolbio.2016.08.004

  4. From Single Cells to Tissues: Interactions between the Matrix and Human Breast Cells in Real Time

    From Single Cells to Tissues: Interactions between the Matrix and Human Breast Cells in Real Time

    PLoS ONE


    Bulk properties do not determine shape; however, localized regions of collagen fiber alignment are required for ductal elongation and branching.

    Manuscript Citation Publisher Full text

    Abstract:

    Background: Mammary gland morphogenesis involves ductal elongation, branching, and budding. All of these processes are mediated by stroma - epithelium interactions. Biomechanical factors, such as matrix stiffness, have been established as important factors in these interactions. For example, epithelial cells fail to form normal acinar structures in vitro in 3D gels that exceed the stiffness of a normal mammary gland. Additionally, heterogeneity in the spatial distribution of acini and ducts within individual collagen gels suggests that local organization of the matrix may guide morphogenesis. Here, we quantified the effects of both bulk material stiffness and local collagen fiber arrangement on epithelial morphogenesis. Results: The formation of ducts and acini from single cells and the reorganization of the collagen fiber network were quantified using time-lapse confocal microscopy. MCF10A cells organized the surrounding collagen fibers during the first twelve hours after seeding. Collagen fiber density and alignment relative to the epithelial surface significantly increased within the first twelve hours and were a major influence in the shaping of the mammary epithelium. The addition of Matrigel to the collagen fiber network impaired cell-mediated reorganization of the matrix and increased the probability of spheroidal acini rather than branching ducts. The mechanical anisotropy created by regions of highly aligned collagen fibers facilitated elongation and branching, which was significantly correlated with fiber organization. In contrast, changes in bulk stiffness were not a strong predictor of this epithelial morphology. Conclusions: Localized regions of collagen fiber alignment are required for ductal elongation and branching suggesting the importance of local mechanical anisotropy in mammary epithelial morphogenesis. Similar principles may govern the morphology of branching and budding in other tissues and organs.

    Keywords: Collagens, Morphogenesis, Extracellular matrix, Gels, Anisotropy, Stiffness, Scanning electron microscopy, Mammary gland development

    Citation:

    Barnes, C., L. Speroni, K. Quinn, M. Montévil, K. Saetzler, G. Bode-Animashaun, G. McKerr, et al. 2014. “From Single Cells to Tissues: Interactions between the Matrix and Human Breast Cells in Real Time.” Edited by Christophe Egles. PLoS ONE 9 (4): e93325. https://doi.org/10.1371/journal.pone.0093325

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