title: FOXO transcription factors and their role in disorders of the female reproductive tract.
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.
authors: Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
authors: Mark
authors: M
authors: Christian
authors: Eric W-F
authors: EW
authors: Lam
authors: Miranda S C
authors: MS
authors: Wilson
authors: Jan J
authors: JJ
authors: Brosens
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D016503:Drug Delivery Systems; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005831:Genital Diseases, Female / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D018384:Oxidative Stress; D011247:Pregnancy; D012098:Reproduction / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors