Cell-based computational model of early ovarian development in mice

Hannah M. Wear, Annika Eriksson, Humphrey Hung Chang Yao, Karen Watanabe-Sailor

    Research output: Contribution to journalArticle

    Abstract

    Despite its importance to reproduction, certain mechanisms of early ovarian development remain a mystery. To improve our understanding, we constructed the first cell-based computational model of ovarian development in mice that is divided into two phases: Phase I spans embryonic day 5.5 (E5.5) to E12.5; and Phase II spans E12.5 to postnatal day 2. We used the model to investigate four mechanisms: in Phase I, (i) whether primordial germ cells (PGCs) undergo mitosis during migration; and (ii) if the mechanism for secretion of KIT ligand from the hindgut resembles inductive cell-cell signaling or is secreted in a static manner; and in Phase II, (iii) that changes in cellular adhesion produce germ cell nest breakdown; and (iv) whether localization of primordial follicles in the cortex of the ovary is due to proliferation of granulosa cells. We found that the combination of the first three hypotheses produced results that aligned with experimental images and PGC abundance data. Results from the fourth hypothesis did not match experimental images, which suggests that more detailed processes are involved in follicle localization. Phase I and Phase II of the model reproduce experimentally observed cell counts and morphology well. A sensitivity analysis identified contact energies, mitotic rates, KIT chemotaxis strength, and diffusion rate in Phase I and oocyte death rate in Phase II as parameters with the greatest impact on model predictions. The results demonstrate that the computational model can be used to understand unknown mechanisms, generate new hypotheses, and serve as an educational tool.

    Original languageEnglish (US)
    Pages (from-to)365-377
    Number of pages13
    JournalBiology of Reproduction
    Volume97
    Issue number3
    StatePublished - Jan 1 2017

    Fingerprint

    Germ Cells
    Granulosa Cells
    Chemotaxis
    Mitosis
    Oocytes
    Reproduction
    Ovary
    Cell Count
    Ligands
    Mortality

    Keywords

    • Cell-based model
    • Computational model
    • Developmental biology
    • Mice
    • Ovarian development
    • Ovary

    ASJC Scopus subject areas

    • Cell Biology

    Cite this

    Cell-based computational model of early ovarian development in mice. / Wear, Hannah M.; Eriksson, Annika; Yao, Humphrey Hung Chang; Watanabe-Sailor, Karen.

    In: Biology of Reproduction, Vol. 97, No. 3, 01.01.2017, p. 365-377.

    Research output: Contribution to journalArticle

    Wear, Hannah M. ; Eriksson, Annika ; Yao, Humphrey Hung Chang ; Watanabe-Sailor, Karen. / Cell-based computational model of early ovarian development in mice. In: Biology of Reproduction. 2017 ; Vol. 97, No. 3. pp. 365-377.
    @article{27c48e752e6240dbaa542f81e8660760,
    title = "Cell-based computational model of early ovarian development in mice",
    abstract = "Despite its importance to reproduction, certain mechanisms of early ovarian development remain a mystery. To improve our understanding, we constructed the first cell-based computational model of ovarian development in mice that is divided into two phases: Phase I spans embryonic day 5.5 (E5.5) to E12.5; and Phase II spans E12.5 to postnatal day 2. We used the model to investigate four mechanisms: in Phase I, (i) whether primordial germ cells (PGCs) undergo mitosis during migration; and (ii) if the mechanism for secretion of KIT ligand from the hindgut resembles inductive cell-cell signaling or is secreted in a static manner; and in Phase II, (iii) that changes in cellular adhesion produce germ cell nest breakdown; and (iv) whether localization of primordial follicles in the cortex of the ovary is due to proliferation of granulosa cells. We found that the combination of the first three hypotheses produced results that aligned with experimental images and PGC abundance data. Results from the fourth hypothesis did not match experimental images, which suggests that more detailed processes are involved in follicle localization. Phase I and Phase II of the model reproduce experimentally observed cell counts and morphology well. A sensitivity analysis identified contact energies, mitotic rates, KIT chemotaxis strength, and diffusion rate in Phase I and oocyte death rate in Phase II as parameters with the greatest impact on model predictions. The results demonstrate that the computational model can be used to understand unknown mechanisms, generate new hypotheses, and serve as an educational tool.",
    keywords = "Cell-based model, Computational model, Developmental biology, Mice, Ovarian development, Ovary",
    author = "Wear, {Hannah M.} and Annika Eriksson and Yao, {Humphrey Hung Chang} and Karen Watanabe-Sailor",
    year = "2017",
    month = "1",
    day = "1",
    language = "English (US)",
    volume = "97",
    pages = "365--377",
    journal = "Biology of Reproduction",
    issn = "0006-3363",
    publisher = "Society for the Study of Reproduction",
    number = "3",

    }

    TY - JOUR

    T1 - Cell-based computational model of early ovarian development in mice

    AU - Wear, Hannah M.

    AU - Eriksson, Annika

    AU - Yao, Humphrey Hung Chang

    AU - Watanabe-Sailor, Karen

    PY - 2017/1/1

    Y1 - 2017/1/1

    N2 - Despite its importance to reproduction, certain mechanisms of early ovarian development remain a mystery. To improve our understanding, we constructed the first cell-based computational model of ovarian development in mice that is divided into two phases: Phase I spans embryonic day 5.5 (E5.5) to E12.5; and Phase II spans E12.5 to postnatal day 2. We used the model to investigate four mechanisms: in Phase I, (i) whether primordial germ cells (PGCs) undergo mitosis during migration; and (ii) if the mechanism for secretion of KIT ligand from the hindgut resembles inductive cell-cell signaling or is secreted in a static manner; and in Phase II, (iii) that changes in cellular adhesion produce germ cell nest breakdown; and (iv) whether localization of primordial follicles in the cortex of the ovary is due to proliferation of granulosa cells. We found that the combination of the first three hypotheses produced results that aligned with experimental images and PGC abundance data. Results from the fourth hypothesis did not match experimental images, which suggests that more detailed processes are involved in follicle localization. Phase I and Phase II of the model reproduce experimentally observed cell counts and morphology well. A sensitivity analysis identified contact energies, mitotic rates, KIT chemotaxis strength, and diffusion rate in Phase I and oocyte death rate in Phase II as parameters with the greatest impact on model predictions. The results demonstrate that the computational model can be used to understand unknown mechanisms, generate new hypotheses, and serve as an educational tool.

    AB - Despite its importance to reproduction, certain mechanisms of early ovarian development remain a mystery. To improve our understanding, we constructed the first cell-based computational model of ovarian development in mice that is divided into two phases: Phase I spans embryonic day 5.5 (E5.5) to E12.5; and Phase II spans E12.5 to postnatal day 2. We used the model to investigate four mechanisms: in Phase I, (i) whether primordial germ cells (PGCs) undergo mitosis during migration; and (ii) if the mechanism for secretion of KIT ligand from the hindgut resembles inductive cell-cell signaling or is secreted in a static manner; and in Phase II, (iii) that changes in cellular adhesion produce germ cell nest breakdown; and (iv) whether localization of primordial follicles in the cortex of the ovary is due to proliferation of granulosa cells. We found that the combination of the first three hypotheses produced results that aligned with experimental images and PGC abundance data. Results from the fourth hypothesis did not match experimental images, which suggests that more detailed processes are involved in follicle localization. Phase I and Phase II of the model reproduce experimentally observed cell counts and morphology well. A sensitivity analysis identified contact energies, mitotic rates, KIT chemotaxis strength, and diffusion rate in Phase I and oocyte death rate in Phase II as parameters with the greatest impact on model predictions. The results demonstrate that the computational model can be used to understand unknown mechanisms, generate new hypotheses, and serve as an educational tool.

    KW - Cell-based model

    KW - Computational model

    KW - Developmental biology

    KW - Mice

    KW - Ovarian development

    KW - Ovary

    UR - http://www.scopus.com/inward/record.url?scp=85044663821&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85044663821&partnerID=8YFLogxK

    M3 - Article

    VL - 97

    SP - 365

    EP - 377

    JO - Biology of Reproduction

    JF - Biology of Reproduction

    SN - 0006-3363

    IS - 3

    ER -