Regulation of mouse primordial follicle formation by signaling through the PI3K pathway

Joshua J.N. Burton, Amanda J. Luke, Melissa E. Pepling

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)515-525
Number of pages11
JournalBiology of Reproduction
Volume106
Issue number3
DOIs
StatePublished - Mar 1 2022

Keywords

  • cyst breakdown
  • oocyte growth
  • PI3K signaling
  • primordial follicle formation

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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