Castrillon Diego H, Miao Lili, Kollipara Ramya, Horner James W, DePinho Ronald A
Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Science. 2003 Jul 11;301(5630):215-8. doi: 10.1126/science.1086336.
Foxo transcription factors have been implicated in diverse biological processes, including metabolism, cellular stress responses, and aging. Here, we show that Foxo3a-/- female mice exhibit a distinctive ovarian phenotype of global follicular activation leading to oocyte death, early depletion of functional ovarian follicles, and secondary infertility. Foxo3a thus functions at the earliest stages of follicular growth as a suppressor of follicular activation. In addition to providing a molecular entry point for studying the regulation of follicular growth, these results raise the possibility that accelerated follicular initiation plays a role in premature ovarian failure, a common cause of infertility and premature aging in women.
叉头框O转录因子（Foxo）已被证明参与多种生物学过程，包括新陈代谢、细胞应激反应和衰老。在此，我们发现Foxo3a基因敲除的雌性小鼠表现出一种独特的卵巢表型，即整体卵泡激活，导致卵母细胞死亡、功能性卵巢卵泡早期耗竭和继发性不孕。因此，Foxo3a在卵泡生长的最早阶段作为卵泡激活的抑制因子发挥作用。这些结果不仅为研究卵泡生长调控提供了一个分子切入点，还提出了加速卵泡起始在卵巢早衰中起作用的可能性，卵巢早衰是女性不孕和早衰的常见原因。
