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Hornless goats. A mutation of the FOXL2 gene induces a sex reversal in female goats that are born with male attributes and no horns.. © INRA, Eric Pailhoux

A guardian gene for female sex

Researchers at INRA have just uncovered one of the major genes responsible for female differentiation: FOXL2. Not only does this gene activate differentiation in the ovary, but it also blocks the expression of male genes within the developing ovary. These results, published in the 30 January 2014 online issue of Current Biology, will help further understanding with regards to certain cases of infertility in female livestock and women.

Updated on 02/27/2014
Published on 01/31/2014

Studying sex reversals for answers

During normal development, the formation of testes or ovaries in a foetus depends on the presence or absence of the SRY gene, carried by the Y chromosome. However, instances of sex reversal have been observed, where foetuses carrying two X chromosomes, which are programmed to develop an ovary, are actually born with all of the characteristics of a male. For more than a decade, researchers at INRA’s Developmental Biology and Reproduction unit in Jouy-en-Josas have been studying and characterising the mutations responsible for XX males in domesticated animal species such as goats, exposing the importance of a gene (FOXL2) carried by an autosome (not a sex chromosome).

To demonstrate this gene's role in determining gender, the researchers successfully silenced the FOXL2 gene in goat embryos using new genetic modification techniques. The XX foetuses that no longer had the FOXL2 gene developed testes instead of ovaries.

Ovaries: to exist, a double front to fight

The female development process was long considered the “default” differentiation process. The experiments carried out by the INRA team prove the opposite: that for ovaries to form, feminine genes must be activated and an active process of silencing must take place to override male development. The FOXL2 gene acts as a defender of the ovary; as the essential female gene, it silences male genes from the moment the ovary begins to form and a priori throughout development and until adulthood.

A model for studying for female fertility

The FOXL2 gene was already thought to play an important role in ovarian function in women. The inactivation of one of the two copies of this gene (heterozygous mutation) can in fact cause premature menopause in young women. Thanks to the techniques elaborated by the Developmental Biology and Reproduction unit, a goat model is currently being created to develop innovative therapies (gene or cell) to treat certain causes of female infertility.

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Animal Physiology and Livestock Systems
Associated Centre(s):
Jouy-en-Josas

Reference

Laurent Boulanger, Maëlle Pannetier, Laurence Gall, Aurélie Allais-Bonnet, Maëva Elzaiat, Daniel Le Bourhis, Nathalie Daniel, Christophe Richard, Corinne Cotinot, Norbert B. Ghyselinck & Eric Pailhoux. FOXL2 is a female sex-determining gene in the goat. Current Biology, 30 January 2014 online issue. DOI: 10.1016/j.cub.2013.12.039