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Computational Modeling and Simulation of Genital Tubercle Development

Metadata Updated: May 2, 2021

Hypospadias is a developmental defect of urethral tube closure that has a complex etiology involving genetic and environmental factors, including anti-androgenic and estrogenic disrupting chemicals; however, little is known about the morphoregulatory consequences of androgen/estrogen balance during genital tubercle (GT) development. Computer models that predictively model sexual dimorphism of the GT may provide a useful resource to translate chemical-target bipartite networks and their developmental consequences across the human-relevant chemical universe. Here, we describe a multicellular agent-based model of genital tubercle (GT) development that simulates urethrogenesis from the sexually-indifferent urethral plate stage to urethral tube closure. The prototype model, constructed in CompuCell3D, recapitulates key aspects of GT morphogenesis controlled by SHH, FGF10, and androgen pathways through modulation of stochastic cell behaviors, including differential adhesion, motility, proliferation, and apoptosis. Proper urethral tube closure in the model was shown to depend quantitatively on SHH- and FGF10-induced effects on mesenchymal proliferation and epithelial apoptosis—both ultimately linked to androgen signaling. In the absence of androgen, GT development was feminized and with partial androgen deficiency, the model resolved with incomplete urethral tube closure, thereby providing an in silico platform for probabilistic prediction of hypospadias risk across combinations of minor perturbations to the GT system at various stages of embryonic development.

This dataset is associated with the following publication: Leung , M.C.K., S. Hutson, A. Seifert, R. Spencer, and T. Knudsen. (REPRODUCTIVE TOXICOLOGY) Computational Modeling and Simulation of Genital Tubercle Development. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 1-11, (2016).

Access & Use Information

Public: This dataset is intended for public access and use. License: See this page for license information.

Downloads & Resources

References

https://doi.org/10.1016/j.reprotox.2016.05.005

Dates

Metadata Created Date November 12, 2020
Metadata Updated Date May 2, 2021

Metadata Source

Harvested from EPA ScienceHub

Additional Metadata

Resource Type Dataset
Metadata Created Date November 12, 2020
Metadata Updated Date May 2, 2021
Publisher U.S. EPA Office of Research and Development (ORD)
Maintainer
Identifier A-dncw-339
Data Last Modified 2016-09-01
Public Access Level public
Bureau Code 020:00
Schema Version https://project-open-data.cio.gov/v1.1/schema
Harvest Object Id 4ad8dc80-91e6-4ba8-8579-b20d35bddeae
Harvest Source Id 04b59eaf-ae53-4066-93db-80f2ed0df446
Harvest Source Title EPA ScienceHub
License https://pasteur.epa.gov/license/sciencehub-license.html
Program Code 020:095
Publisher Hierarchy U.S. Government > U.S. Environmental Protection Agency > U.S. EPA Office of Research and Development (ORD)
Related Documents https://doi.org/10.1016/j.reprotox.2016.05.005
Source Datajson Identifier True
Source Hash 7b20e056b95d017ea56c7f0737d9cb266e774161
Source Schema Version 1.1

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