Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation

N. Henriette Uhlenhaut, Susanne Jakob, Katrin Anlag, Tobias Eisenberger, Ryohei Sekido, Jana Kress, Anna-Corina Treier, Claudia Klugmann, Christian Klasen, Nadine I. Holter, Dieter Riethmacher, Guenther Schutz, Austin J. Cooney, Robin Lovell-Badge, Mathias Treier*

*Corresponding author for this work

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553 Citations (Scopus)

Abstract

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.

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Original languageEnglish
Pages (from-to)1130-1142
Number of pages13
JournalCell
Volume139
Issue number6
DOIs
Publication statusPublished - 11 Dec 2009

Keywords

  • beta-catenin
  • transcription factor FOXL2
  • germ-cells
  • reversal
  • mammalian gonad
  • sry action
  • pre-sertoli cells
  • SOX9
  • differentiation
  • gene-transcription

Cite this

Uhlenhaut, N. H., Jakob, S., Anlag, K., Eisenberger, T., Sekido, R., Kress, J., Treier, A-C., Klugmann, C., Klasen, C., Holter, N. I., Riethmacher, D., Schutz, G., Cooney, A. J., Lovell-Badge, R., & Treier, M. (2009). Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell, 139(6), 1130-1142. https://doi.org/10.1016/j.cell.2009.11.021