Somatic Sex Reprogramming of Adult Ovaries to Testes by FOXL2 Ablation
Somatic Sex Reprogramming of Adult Ovaries to Testes by FOXL2 Ablation
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DOI：
10.1016/j.cell.2009.11.021
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发表时间：
2009-12-11
期刊：
影响因子：
64.5
通讯作者：
Treier, Mathias
中科院分区：
文献类型：
--
作者：
Uhlenhaut, N. Henriette;Jakob, Susanne;Treier, Mathias
在哺乳动物中，由Y染色体编码的转录因子SRY通常负责触发中性性腺发育为睾丸而不是卵巢。然而，睾丸分化可以在其缺失的情况下发生。在这里，我们证明在小鼠中，一个单一的因素，叉头转录调节FOXL2，需要防止转分化的成年卵巢睾丸。成年卵泡中Foxl2的诱导性缺失导致睾丸特异性基因的立即上调，包括关键SRY靶基因Sox 9。一致地，颗粒细胞和卵泡膜细胞谱系重编程为支持样细胞谱系和间质样细胞谱系，其睾酮水平与正常XY雄性同窝仔的睾酮水平相当。我们的研究结果表明，卵巢表型的维持是一个活跃的过程，在整个生命。它们也可能对理解和治疗儿童性发育障碍和女性过早绝经具有重要的医学意义。有关本文的视频摘要，请参阅PaperFlick文件和在线补充数据。
In mammals, the transcription factor SRY, encoded by the Y chromosome, is normally responsible for triggering the indifferent gonads to develop as testes rather than ovaries. However, testis differentiation can occur in its absence. Here we demonstrate in the mouse that a single factor, the forkhead transcriptional regulator FOXL2, is required to prevent transdifferentiation of an adult ovary to a testis. Inducible deletion of Foxl2 in adult ovarian follicles leads to immediate upregulation of testis-specific genes including the critical SRY target gene Sox9. Concordantly, reprogramming of granulosa and theca cell lineages into Sertoli-like and Leydig-like cell lineages occurs with testosterone levels comparable to those of normal XY male littermates. Our results show that maintenance of the ovarian phenotype is an active process throughout life. They might also have important medical implications for the understanding and treatment of some disorders of sexual development in children and premature menopause in women.For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.