Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
Cell. 2009 Dec 11;139(6):1130-42. doi: 10.1016/j.cell.2009.11.021.
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.
在哺乳动物中，Y 染色体编码的转录因子 SRY 通常负责促使未分化的性腺发育为睾丸而不是卵巢。然而，在其缺失的情况下，睾丸也可以分化。在这里，我们在小鼠中证明，单一因子叉头转录调节因子 FOXL2 是防止成年卵巢向睾丸转分化所必需的。在成年卵巢滤泡中诱导性删除 Foxl2 会立即上调睾丸特异性基因，包括关键的 SRY 靶基因 Sox9。相应地，颗粒细胞和膜细胞谱系向类似于 Sertoli 细胞和 Leydig 细胞的谱系重编程伴随着与正常 XY 雄性同窝仔相似的睾酮水平。我们的结果表明，卵巢表型的维持是一个贯穿一生的主动过程。它们对于理解和治疗儿童某些性发育障碍和女性过早绝经也可能具有重要的医学意义。
