Abstract
All fundamental reproductive events in the human ovary and uterus, including ovulation, implantation and menstruation, are dependent upon profound tissue remodelling, characterized by cyclical waves of cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown and regeneration. Although the rise and fall in ovarian hormones, estradiol and progesterone, orchestrate these reproductive events, FOXO transcription factors, an evolutionary conserved subfamily of forkhead transcription factors, have emerged major downstream effector molecules, capable of integrating hormonal cues with a variety of stress, growth factor and cytokine signal transduction pathways. The ability of FOXOs to regulate seemingly opposing cellular responses, ranging from cell cycle arrest and oxidative stress responses to differentiation and apoptosis, renders these transcription factors indispensable for cyclic tissue remodelling in the reproductive tract. Aberrant expression or perturbed activity of FOXO transcription factors are increasingly linked to prevalent reproductive disorders, such as endometriosis, endometrial cancer, primary ovarian insufficiency and pregnancy failure, which in turn highlights their potential as therapeutic targets.
Keywords: FOXO, transcription, apoptosis, ovary, endometrium, endometriosis, cancer, therapy, Drosophila, polyubiquitination, Caenorhanditis elegans, Daf-16, FASLG, endometrial cancer
Current Drug Targets
Title: FOXO Transcription Factors and their Role in Disorders of the Female Reproductive Tract
Volume: 12 Issue: 9
Author(s): Mark Christian, Eric W.-F. Lam, Miranda S.C. Wilson and Jan J. Brosens
Affiliation:
Keywords: FOXO, transcription, apoptosis, ovary, endometrium, endometriosis, cancer, therapy, Drosophila, polyubiquitination, Caenorhanditis elegans, Daf-16, FASLG, endometrial cancer
Abstract: All fundamental reproductive events in the human ovary and uterus, including ovulation, implantation and menstruation, are dependent upon profound tissue remodelling, characterized by cyclical waves of cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown and regeneration. Although the rise and fall in ovarian hormones, estradiol and progesterone, orchestrate these reproductive events, FOXO transcription factors, an evolutionary conserved subfamily of forkhead transcription factors, have emerged major downstream effector molecules, capable of integrating hormonal cues with a variety of stress, growth factor and cytokine signal transduction pathways. The ability of FOXOs to regulate seemingly opposing cellular responses, ranging from cell cycle arrest and oxidative stress responses to differentiation and apoptosis, renders these transcription factors indispensable for cyclic tissue remodelling in the reproductive tract. Aberrant expression or perturbed activity of FOXO transcription factors are increasingly linked to prevalent reproductive disorders, such as endometriosis, endometrial cancer, primary ovarian insufficiency and pregnancy failure, which in turn highlights their potential as therapeutic targets.
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Cite this article as:
Christian Mark, W.-F. Lam Eric, S.C. Wilson Miranda and J. Brosens Jan, FOXO Transcription Factors and their Role in Disorders of the Female Reproductive Tract, Current Drug Targets 2011; 12 (9) . https://dx.doi.org/10.2174/138945011796150253
DOI https://dx.doi.org/10.2174/138945011796150253 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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