FOXO transcription factors: from cell fate decisions to regulation of human female reproduction.
All key reproductive events in the human ovary and uterus, including follicle activation, ovulation, implantation, decidualization, luteolysis and menstruation, are dependent upon profound tissue remodelling, characterised by cyclical waves of cell proliferation, differentiation, apoptosis, tissue breakdown and regeneration. FOXO transcription factors, an evolutionarily conserved subfamily of the forkhead transcription factors, have emerged as master regulators of cell fate decision capable of integrating avariety of stress, growth factor and cytokine signaling pathways with the transcription machinery. 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 female reproduction. Conversely, perturbations in the expression or activity of FOXO transcription factors are increasingly linked to common reproductive disorders, such as pregnancy loss, endometriosis, endometrial cancer and primary ovarian insufficiency.
Brosens
Jan J
JJ
Institute of Reproductive and Developmental Biology Imperial College London, Hammersmith Campus, London W12 0NN, UK. j.brosens@imperial.ac.uk
Wilson
Miranda S C
MS
Lam
Eric W F
EW
D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D005260:Female; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006801:Humans; D011247:Pregnancy; D012098:Reproduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D018797:Cell Cycle Proteins; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; C108803:FOXO4 protein, human; C478770:FOXO6 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D014157:Transcription Factors