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Review
. 2021 Sep 20:12:730196.
doi: 10.3389/fphys.2021.730196. eCollection 2021.

The Signaling Pathways Involved in Ovarian Follicle Development

Liyuan Li  1   2 , Xiaojin Shi  1 , Yun Shi  3 , Zhao Wang  1
Affiliations
Review

The Signaling Pathways Involved in Ovarian Follicle Development

Liyuan Li et al. Front Physiol. .

Abstract

The follicle is the functional unit of the ovary, which is composed of three types of cells: oocytes, granulosa cells, and theca cells. Ovarian follicle development and the subsequent ovulation process are coordinated by highly complex interplay between endocrine, paracrine, and autocrine signals, which coordinate steroidogenesis and gametogenesis. Follicle development is regulated mainly by three organs, the hypothalamus, anterior pituitary, and gonad, which make up the hypothalamic-pituitary-gonadal axis. Steroid hormones and their receptors play pivotal roles in follicle development and participate in a series of classical signaling pathways. In this review, we summarize and compare the role of classical signaling pathways, such as the WNT, insulin, Notch, and Hedgehog pathways, in ovarian follicle development and the underlying regulatory mechanism. We have also found that these four signaling pathways all interact with FOXO3, a transcription factor that is widely known to be under control of the PI3K/AKT signaling pathway and has been implicated as a major signaling pathway in the regulation of dormancy and initial follicular activation in the ovary. Although some of these interactions with FOXO3 have not been verified in ovarian follicle cells, there is a high possibility that FOXO3 plays a core role in follicular development and is regulated by classical signaling pathways. In this review, we present these signaling pathways from a comprehensive perspective to obtain a better understanding of the follicular development process.

Keywords: Hedgehog signaling; Notch signaling; PI3K-AKT signaling; WNT signaling; follicular development; insulin signaling.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic displaying classical signaling pathways (WNT, insulin, Notch, and Hedgehog) and their interaction with PI3K/AKT-FOXO3 during ovarian follicle development.
See this image and copyright information in PMC

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