Institute of Reproductive and Developmental Biology Imperial College London, Hammersmith Campus, London W12 0NN, UK.
Adv Exp Med Biol. 2009;665:227-41. doi: 10.1007/978-1-4419-1599-3_17.
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.
人类卵巢和子宫中的所有关键生殖事件，包括卵泡激活、排卵、着床、蜕膜化、黄体溶解和月经，都依赖于深刻的组织重塑，其特征是细胞增殖、分化、凋亡、组织分解和再生的周期性波动。FOXO 转录因子是叉头转录因子进化上保守的亚家族，已成为细胞命运决定的主要调节剂，能够将各种应激、生长因子和细胞因子信号通路与转录机制整合在一起。FOXOs 调节看似相反的细胞反应的能力，从细胞周期停滞和氧化应激反应到分化和凋亡，使这些转录因子在女性生殖的周期性组织重塑中不可或缺。相反，FOXO 转录因子的表达或活性的改变与常见的生殖障碍有关，如流产、子宫内膜异位症、子宫内膜癌和原发性卵巢功能不全。
