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Recapitulating Human Ovarian Aging Using Random Walks by Joshua Johnson; John W. Emerson; Sean D. Lawley is a Environmental Science article available to read on EtoBox.

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Mechanism(s) that control whether individual human primordial ovarian follicles (PFs) remain dormant, or begin to grow, are all but unknown. One of our groups has recently shown that activation of the Integrated Stress Response (ISR) pathway can slow follicular granulosa cell proliferation by activating cell cycle checkpoints. Those data suggest that the ISR is active and fluctuates according to local conditions in dormant PFs. Because cell cycle entry of (pre)granulosa cells is required for PF growth activation (PFGA), we propose that rare ISR checkpoint resolution allows individual PFs to begin to grow. Fluctuating ISR activity within individual PFs can be described by a random process. In this article, we model ISR activity of individual PFs by one-dimensional random walks (RWs) and monitor the rate at which simulated checkpoint resolution and thus PFGA threshold crossing occurs. We show that the simultaneous recapitulation of (i) the loss of PFs over time within simulated subjects, and (ii) the timing of PF depletion in populations of simulated subjects equivalent to the distribution of the human age of natural menopause can be produced using this approach. In the RW model, the

Who reads Recapitulating Human Ovarian Aging Using Random Walks?

Author

Joshua Johnson; John W. Emerson; Sean D. Lawley

Publisher

PeerJ

Published

2022

Language

EN

Field

Environmental Science (Physical Sciences)