14 August 2017 Cell-based computational model of early ovarian development in mice
Hannah M. Wear, Annika Eriksson, Humphrey Hung-Chang Yao, Karen H. Watanabe
Author Affiliations +

Despite its importance to reproduction, certain mechanisms of early ovarian development remain amystery. To improve our understanding, we constructed the first cell-based computationalmodel 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) undergomitosis duringmigration; 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.

Summary Sentence

We have constructed a cell-based model that simulates the signaling and morphological development involved in early ovarian development in mice, from first detection of primordial germ cells to formation of primordial follicles.

© The Author 2017. Published by Oxford University Press Society for the Study of Reproduction. All rights reserved. This article includes contributions by US Federal Government employees.
Hannah M. Wear, Annika Eriksson, Humphrey Hung-Chang Yao, and Karen H. Watanabe "Cell-based computational model of early ovarian development in mice," Biology of Reproduction 97(3), 365-377, (14 August 2017). https://doi.org/10.1093/biolre/iox089
Received: 2 May 2017; Accepted: 9 August 2017; Published: 14 August 2017
cell-based model
computational model
developmental biology
ovarian development
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