Careful with that X, you gene

December 28, 2009

A couple of weeks ago, Cell magazine published an article (Somatic Sex Reprogramming of Adult Ovaries to Testes by FOXL2 Ablation) by a group of scientists confirming that their research on mice has revealed that “the activity of a single gene, FOXL2, is all that prevents adult ovary cells turning into cells found in testes”.

In other words, sex is not determined by chromosomes alone; genes in the autosomes play a significant part in the process.

From the News section of the National Institute of Medical Research (NIMR) website:

The decision as to whether a developing embryo will become a male or a female is taken at an early stage during the formation of the gonads. In an XY embryo, the Y chromosome gene Sry triggers the formation of testes. Substances made by the testes, particularly the hormone testosterone, then cause the development of male characteristics throughout the rest of the embryo. In an XX embryo Sry is not present, so ovaries will develop instead of testes, and female characteristics will develop because the male-promoting substances are absent. However, Sry is only active for a brief period in the early embryonic gonads, and it works by activating a gene that is neither on the X or Y chromosome but on one of the other pairs of chromosomes common to males and females. This gene, termed Sox9, functions to promote and then maintain the formation of Sertoli cells in the testes, cells that support and nourish developing sperm. Sox9 is active in Sertoli cells throughout life. If Sry is absent and Sox9 fails to be activated, then cells of the same original type become follicle cells, which serve to support growing eggs (oocytes) in the ovary. Because Sry, Sox9 and testosterone are all male-promoting, so that in their absence female characteristics will develop, it had been considered that female development happens by default.

Robin Lovell-Badge from NIMR’s Division of Stem Cell Biology and Developmental Genetics, in collaboration with Matthias Treier and colleagues at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have shown that the activity of a single gene, Foxl2, is all that is required to prevent cells typical of an adult ovary from turning into those present in testes. When the gene is deleted from adult female mice, the cells rapidly change and begin to make male-specific factors including the male hormone testosterone. Moreover, these cells organize themselves into structures resembling sperm producing tubules – although these tubules are empty because the eggs cannot change to become sperm. This work shows very clearly that the male pathway needs to be actively suppressed in the adult.

That’s the science, but what of the implications? Assuming that the same findings hold true for humans as they do for mice, then there are potentially several advances in the field of reproductive medicine. From the NIMR report again:

[…] For example, [these findings] may help to understand and treat some of the masculinising effects of menopause seen in some women, and some cases of premature ovarian failure where women lose all their oocytes early. It also offers for the first time the suggestion, although one that is still very speculative, that it might eventually be feasible to help treat some disorders of sex differentiation in children, for example, when XY individuals develop ovaries or perhaps when XX individuals develop testes or in intersex conditions. In some such cases it may be possible to retain fertility, which is otherwise inevitably compromised. Similarly, if it is possible to change adult gonad type from ovary to testes or even the reverse, it may eventually allow individuals with gender dysphoria, who feel they are trapped in the wrong sex, to change their gonads appropriately rather than having them removed surgically as part of their treatment to undergo gender reassignment. In such cases, however, while the new gonads might make the right hormones for their new sex, these individuals will lose their fertility.

To be honest, the only immediate benefit of this discovery that I can see is that, to quote Sophia Siedlberg at Intersex News:

the unholy dictatorship of “XX or XY” is over

I’ve no great wish to get bogged down in another interminable discussion of the nature/nurture dichotomy as applied to transsexual women, even so, it seems obvious that being able to ‘flip the FOXL2 switch’ would not instantly end an individual’s gender dysphoria. Unlike stem cell research, where I can imagine that – eventually – there may be the possibility of a body developing appropriate genitalia, it seems that with any FOXL2 therapy, surgery would still be required. And, of course, it would still not be a matter of ‘taking the blue pill’ and instantly becoming a woman; questions still remain around such factors as socialisation, gender roles and presentation, etc. And it seems likely that gender dissonance will still be invisible to an obstetrician, so the opportunity to activate the FOXL2 gene in utero, when it might, arguably, be most effective, will be lost.

Finally, there’s the ever-present risk that any benefits of such an emerging biotechnology will be co-opted by politicians and other vested interests, to advance the cause of eugenics as a tool for greater enforcement of a heteronormative gender binary whilst simultaneously permitting drug companies to increase their profits still further.

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Cross-posted at Questioning Transphobia

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6 Responses to “Careful with that X, you gene”


  1. I’d like a pink pill pleeezz:)

  2. earwicga Says:

    Wow at the video. Relics is the only album I bought in 3 formats (LP/tape/CD) and now I have discovered there is a re-mastered version so I will have to go buy that now!

  3. Helen G Says:

    I think the vid is from ‘Live At Pompeii’ and I know there’s another version on the ‘Ummagumma’ album. Spot the old hippy, eh? :)

  4. earwicga Says:

    I’m more of an old rocker. It’s easier to go through YouTube for a reminisce than all the old LP’s I hang on for god knows what reason!?!

  5. Sophia Says:

    I suppose you don’t want to hear about the involvement with lager above the car entrance ? No ? Very wise…


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