|Cell. 2009 Dec 11;139(6):1051-3. |
Females battle to suppress their inner male.
Sinclair A, Smith C.
Murdoch Children's Research Institute, Melbourne, Victoria 3052, Australia. email@example.com
Conventional wisdom holds that the ovary and testis are terminally differentiated organs in adult mammals. However, Uhlenhaut et al. (2009) now report that deletion of a single gene, Foxl2, is sufficient to induce transdifferentiation of ovary into testis in adult mice, suggesting that testicular development is actively repressed throughout the life of females.
|Cell. 2009 Dec 11;139(6):1130-42. |
Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.
Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier AC, Klugmann C, Klasen C, Holter NI, Riethmacher D, Schütz G, Cooney AJ, Lovell-Badge R, Treier M.
Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
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.