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1 November 2021 Regulation of mouse primordial follicle formation by signaling through the PI3K pathway
Joshua J. N. Burton, Amanda J. Luke, Melissa E. Pepling
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Abstract

Cell signaling mediated by the KIT receptor is critical for many aspects of oogenesis including the proliferation and migration of primordial germ cells, as well as the survival, growth, and maturation of ovarian follicles. We previously showed that KIT regulates cyst breakdown and primordial follicle formation, and in this study, have investigated the mechanisms downstream of the receptor by modulating the activity of two downstream signaling cascades: the phosphoinositide 3-kinase (PI3K) and the mitogen-activated protein kinase pathways. E17.5 ovaries were cultured for 5 days with a daily dose of media supplemented with either the PI3K inhibitor LY294002, the MEK inhibitor U0126, or a DMSO vehicle control. Our histological observations aligned with the established role of PI3K in oocyte growth and primordial follicle activation but also revealed that LY294002 treatment delayed the processes of cyst breakdown and primordial follicle formation. U0126 treatment also led to a reduction in oocyte growth and follicle development but did not appear to affect cyst breakdown. The delay in cyst breakdown was mitigated when ovaries were dually dosed with LY294002 and KITL, suggesting that while KIT may signal through PI3K to promote cyst breakdown, other signaling networks downstream of the receptor could compensate. These observations unearth a role for PI3K signaling in the establishment of the ovarian reserve and suggest that PI3K might be the primary mediator of KIT-induced cyst breakdown and primordial follicle formation in the mouse ovary.

Summary sentence PI3K signaling promotes cyst breakdown and primordial follicle formation in mice.

Graphical Abstract

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© The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Joshua J. N. Burton, Amanda J. Luke, and Melissa E. Pepling "Regulation of mouse primordial follicle formation by signaling through the PI3K pathway," Biology of Reproduction 106(3), 515-525, (1 November 2021). https://doi.org/10.1093/biolre/ioab204
Received: 18 June 2021; Accepted: 27 October 2021; Published: 1 November 2021
KEYWORDS
cyst breakdown
oocyte growth
PI3K signaling
primordial follicle formation
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