IMR Press / FBL / Volume 12 / Issue 10 / DOI: 10.2741/2339

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death
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1 Departments of Obstetrics and Gynecology and Cellular and Molecular Medicine, University of Ottawa, Ottawa Health Research Institute, The Ottawa Hospital (Civic Campus) Ottawa, ON, Canada, K1Y 4E9, Canada
2 Department of Obstetrics and Gynecology, University of Fukui, Matsuoka, Fukui, 910-1193, Japan
3 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China
4 Department of Obstetrics and Gynecology, Morehouse School of Medicine, Atlanta, GA 30310, USA
Academic Editor:Yi-Xun Liu
Front. Biosci. (Landmark Ed) 2007, 12(10), 3628–3639; https://doi.org/10.2741/2339
Published: 1 May 2007
(This article belongs to the Special Issue Gene regulation and signal transduction in gonads)
Abstract

Regulation of mammalian follicular development is tightly regulated by both cell death and survival signals, including endocrine (e.g. gonadotropin) and intra-ovarian regulators (e.g. Nodal and GDF9). The destiny of the individual follicle (growth/ovulation or atresia) is dependent on a delicate balance in the expression and action of factors promoting follicular cell proliferation, growth and differentiation, and of those promoting programmed cell death (apoptosis). Development of the follicle from the primordial to preantral stage is regulated by oocyte-derived factors including GDF9 and BMP15, and is not dependent on gonadotropin support (gonadotropin-independent stage). As the follicle transits into the early antral stage it becomes responsive to gonadotropin (gonadotropin-responsive stages) and further development renders the follicle completely dependent on the presence of gonadotropin while modulated by intra-ovarian regulators (gonadotropin-dependent). Follicle fate is also regulated by pro-apoptotic factors such as the intraovarian regulator Nodal, which is secreted by the theca and promotes apoptosis of differentiated granulosa cells through a mechanism involving Smad2 signaling and suppression of the PI3K/Akt pathway. The intracellular protein prohibitin (PHB) appears to have a dual role during folliculogenesis; acting as a cell survival factor in undifferentiated cells, and as a pro-apoptotic factor following differentiation. Further investigations of the interplay between these endocrine and ovarian regulators will lead to a better understanding into the regulation of follicular development and atresia, allowing development of new techniques for assisted reproduction.

Keywords
Ovary
Cytokine
Follicle
Development
Atresia
FSH
Nodal
Growth and differentiation factor
GDF9
Prohibitin
Reivew
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