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Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation

Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation
Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation
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.
0092-8674
1130-1142
Uhlenhaut, N. Henriette
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Jacob, Susanne
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Anlag, Katrin
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Eisenberger, Tobias
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Sekido, Ryohei
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Kress, Jana
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Treier, Anna-Corina
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Klugmann, Claudia
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Klasen, Christian
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Holter, Nadine I.
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Riethmacher, Dieter
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Schütz, Günther
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Cooney, Austin J.
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Lovell-Badge, Robin
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Treier, Mathias
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Uhlenhaut, N. Henriette
2c4eebd8-7095-40c9-94db-d27e4ff9e52f
Jacob, Susanne
f0f35454-12e7-4de4-bcd9-5ecb4bbff112
Anlag, Katrin
6343b0e8-2e48-41ce-84ec-1c947877aaad
Eisenberger, Tobias
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Sekido, Ryohei
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Kress, Jana
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Treier, Anna-Corina
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Klugmann, Claudia
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Klasen, Christian
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Holter, Nadine I.
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Riethmacher, Dieter
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Schütz, Günther
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Cooney, Austin J.
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Lovell-Badge, Robin
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Treier, Mathias
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Uhlenhaut, N. Henriette, Jacob, Susanne, Anlag, Katrin, Eisenberger, Tobias, Sekido, Ryohei, Kress, Jana, Treier, Anna-Corina, Klugmann, Claudia, Klasen, Christian, Holter, Nadine I., Riethmacher, Dieter, Schütz, Günther, Cooney, Austin J., Lovell-Badge, Robin and Treier, Mathias (2009) Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell, 139 (6), 1130-1142. (doi:10.1016/j.cell.2009.11.021). (PMID:20005806)

Record type: Article

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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More information

Submitted date: 19 July 2009
Published date: 11 December 2009
Organisations: Human Genetics

Identifiers

Local EPrints ID: 71591
URI: http://eprints.soton.ac.uk/id/eprint/71591
ISSN: 0092-8674
PURE UUID: 02cabf80-2576-4279-8112-4ba01e61fe40
ORCID for Dieter Riethmacher: ORCID iD orcid.org/0000-0002-4206-5529

Catalogue record

Date deposited: 15 Dec 2009
Last modified: 14 Mar 2024 02:53

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Contributors

Author: N. Henriette Uhlenhaut
Author: Susanne Jacob
Author: Katrin Anlag
Author: Tobias Eisenberger
Author: Ryohei Sekido
Author: Jana Kress
Author: Anna-Corina Treier
Author: Claudia Klugmann
Author: Christian Klasen
Author: Nadine I. Holter
Author: Dieter Riethmacher ORCID iD
Author: Günther Schütz
Author: Austin J. Cooney
Author: Robin Lovell-Badge
Author: Mathias Treier

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