Forget love, biological sex is a battlefield

By Maggie Koerth-Baker at 2:49 pm Thu, Nov 17, 2011

Gender isn’t a simple thing. A person can be male, female, both, neither, and more—and that identity doesn’t have to have anything to do with the particular genital plumbing they were born with.

But the plumbing itself—the biological sex, rather than gender or socio-cultural sex—is also a lot more complicated (and interesting) than we often give it credit for. Don’t believe me? Then check out “DMRT1 prevents female reprogramming in the postnatal mammalian testis,” a research letter published in September in the journal Nature.

That title is full of typical peer-reviewed paper jargon, but let me break it down for you: There’s a genetic factor, present in male mammals, that is vital to making sure those mammals develop male sex characteristics. But it’s not only important during embryonic development. Oh, no. Turns out, this factor must be active in order for a male’s gonads to stay 100% male. Turn it off, even in an adult male, and the cells in his testes will start to take on more feminine characteristics.

The genetic factor is called DMRT1, and it is not the only thing responsible for maintaining a mammal’s biological sex throughout life. There’s another factor, called FoxL2, that does the same job in females. Scientists already knew about the lifelong necessity of FoxL2. This new research, performed by a team led by Drs. David Zarkower and Vivian Bardwell of the University of Minnesota, confirmed that DMRT1 is FoxL2’s male counterpart.

It all begins in utero. Mammals—both the mice used in this study, and larger creatures like us—start out effectively sexless, with gonadal organs that aren’t yet either ovaries or testicles. The chromosomes the embryo has determine how the gonads develop, and the hormones produced by the gonads determine a lot of other physical sex characteristics. If the embryo is XY, the gonads will develop into testicles. If it’s XX, the gonads will become ovaries. I’m simplifying a lot here, but this will give you the basic jist.*

Both DMRT1 and FoxL2 are transcription factors, proteins that control how genetic information gets copied and expressed. They both exist in gonad cells, but the presence or absence of a Y chromosome determines which factor gets to take charge, and which genetic information is put to use. With a Y chromosome, DMRT1 is activated, and it turns undifferentiated gonadal cells into sperm-nurturing Sertoli cells. Without a Y chromosome, FoxL2 takes over, and those same undifferentiated gonadal cells become granulosa cells, which play several important roles in the ovaries. These transcription factors aren’t the only things governing the expression of sex characteristics, but they are important.

Zarkower and Bardwell’s team compared normal male mice to mutant males that were born lacking a DMRT1 transcription factor. On the surface, the mutant males looked physically male. They had testicles and a penis. But the cells that made up their testicles weren’t normal. By 28 days after birth, most of the testicular cells were expressing FoxL2. The mice looked male on the outside, but inside their gonadal cells were more like those of a female.

Next, the team tried deleting the DMRT1 transcription factor in adult male mice that had been born normal. Over time, these mice also began to show cellular changes toward FoxL2 expression and cells that behaved more like female granulosa cells than male Sertoli cells. Previous research by other scientists demonstrated that the same basic thing is true for females and FoxL2, Dr. Zarkower told me. Just reversed.

Turns out, biological sex determination in mice is kind of an ongoing battle. It doesn’t end during fetal development. It doesn’t even end at birth.

What’s that mean for humans? This part isn’t really clear yet. Naturally-occuring DMRT1 deletions are rare, but they do happen. They can end in a range of effects. Some genetic males born without DMRT1 have small or underdeveloped testes. Others are born with indeterminate physical sex. About 30% of the time, Zarkower said, a natural DMRT1 deletion leads to an XY female—someone who looks physically female on the outside, but who has male genes and nonfunctional gonads instead of either testicles or ovaries. Usually, nobody notices the difference until the person doesn’t experience a normal female puberty.

Because of that, I wondered whether DMRT1 could be useful for women whose biological sex doesn’t match their female gender identity. If deleting DMRT1 can make an adult male body become more feminized, could doctors someday use that trick to intentionally help transition a biologically male body into a more female one?

Unfortunately, Zarkower doubts that would work. “This is very new and there’s a lot we don’t know yet, but the external genitalia didn’t change,” he said. “DMRT1 null mice were born physically male, they just didn’t go through puberty properly. In adults, this was basically the same as removing the testes. There would be hormonal changes, but it wouldn’t have an appreciable effect for external genitalia.”

Beyond that, he said, what happens in mice may or may not translate to humans. For instance, because of the way our genes work, all male mammals have two copies of DMRT1. Mice don’t seem to need both. If you delete one of the copies in a male mouse, the mouse will be essentially normal. Humans, on the other hand, have to have both copies for normal development. More problematic, in humans, mutations of DMRT1 are strongly linked to testicular cancer. “I’d be reluctant to mess around with this in humans,” Zarkower said.

For now, the main thing we can take away from this discovery is a gentle reminder that our bodies really are weird and wonderful. Even if you’re already used to thinking about gender as a fluid concept, it can be strange to realize how flexible biological sex is, as well. Don’t get too hung up on the idea that “male” and “female” must be set-in-stone categories. Nature certainly doesn’t treat sex that way.

*Interestingly, other species of animals have very different processes of determining biological sex. For instance, while those gonadal hormones are key for mammals, birds have cells that are individually male or female from the beginning. Because of that, it’s actually possible to have a chicken whose sex is split down the middle of its body—with one side made up of female cells that produce female sexual characteristics and the other side full of male cells that produce male sexual characteristics. When that happens, the bird is called a gyndandromorph. You can read more about that on Ed Yong’s Not Exactly Rocket Science.

Image: Fig leaves, a Creative Commons Attribution (2.0) image from epredator's photostream

Published 2:49 pm Thu, Nov 17, 2011

About the Author

Maggie Koerth-Baker is the science editor at BoingBoing.net. From August 2014-May 2015, she will be a Nieman-Berkman Fellow at Harvard University. You can follow Maggie's adventures in the Ivory Tower by subscribing to The Fellowship of Three Things newsletter.

More at Boing Boing

The Graffiti Rock TV Pilot

Part 1 of a strip detailing the infamous dance television show that never became a series. The latest from Ed Piskor's Hip Hop Family Tree.

The limits of animal life on Tatooine

Maggie Koerth-Baker on why the megafauna of George Lucas' parched desert world makes no sense. It's not the dry heat that's the problem; it's the food supply.

38 Responses to “Forget love, biological sex is a battlefield”

  1. Stay_Sane_Inside_Insanity says:

    Typo: “For now, the main thing we can take away from this discovery is a gentle
    reminder that are bodies really are weird and wonderful.”

    Should be “our.” 

    Carry on. 

  2. Andrea James says:

    This is a great overview. Most humans’ sex is assigned based on phenotype at birth. Now and then they need to bring in “experts” who enforce the existing paradigm by forcing those with “ambiguous” genitalia into one category or the other. Humans do the same thing to other animals (look up “chick sexing”). The chromosomal concept of XX and XY has come into public consciousness because it reifies the existing binary for a society organized around reproduction, but it’s clear that all animals, including humans, have much more nuance and shading than a simple either/or binary allows.

  3. thebelgianpanda says:

    Because of that, I wondered whether DMRT1 could be useful for women whose biological sex doesn’t match their female gender identity. If deleting DMRT1 can make an adult male body become more feminized, could doctors someday use that trick to intentionally help transition a biologically male body into a more female one?

    I’ve been trying to write a coherent, thoughtful post about this for, I dunno, fifteen minutes.  I just can’t.  So I guess I’ll just say ‘good for people that can use this information to make their lives better’, and ‘fuck those assholes that use this information to oppress people further’. 

    • Daen de Leon says:

      I can imagine developing small interfering RNA (siRNA) elements to bl0ck DMRT1 expression … but you’d probably need to keep those topped up, or you’d turn male again …

  4. Daen de Leon says:

    Thanks for this Maggie!  Cogent, coherent, and thought-provoking – the best of boingboing!

  5. Gordon McMillan says:

    A standing ovation for Maggie. This is an excellent piece of writing. And fascinating as well.

  6. Tess says:

    This is beautifully written, thoughtful, and nuanced, Maggie.  <3

  7. Tom Finland says:

    Interesting article but the use of the word ‘normal’ was a bit off-putting. 

    • Totally understand that. I tried to write this story without using the word “normal”, but it was making the explanation of the research really confusing. I needed a word to quickly explain which mice I was talking about in context, and that was the only one that made sense. My apologies. 

      • Matt Valley says:

        There is nothing wrong with using the word “normal” in a scientific context.  In this case, the norm was the unperturbed group (or control or baseline), and if they were not normal the experiment would not be properly designed.  With a concept like gender, people are justifiably wrong to use this word since a continuum is inaccurately described as normal, but please don’t dismiss a useful word when it is used properly.

        *edit* sorry to see that this has become the thread topic. It was a great article and a fine piece of scientific writing for laypeople.

  8. Sean McKibbon says:

    Ok, so beyond the question of external physical gender , does DMRT1 or  FoxL2 play a role in brain structure or the mental perception of one’s own gender? Is “late onset” transitioning a product of psychological factors such learning to accept yourself or are there hormonal factors?

    • Sean, I don’t think DMRT1 or FoxL2 is a brain or mental perception thing, except to the extent that they help trigger hormone release which might play a role in gendering the brain. 

      Is “late onset” transitioning a product of learning to accept yourself or are thre biological factors?

      I’m not quite sure what you’re asking here, but I am pretty sure it’s outside the purview of this particular research paper. Like I said, we can’t read a whole lot into this paper when it comes to humans. Other than to just say, “Hey, biological sex is more complicated than we give it credit for.” 

  9. Alan Ball says:

    See this is why I decided to stay away from biology. Even the stuff we thought were PRETTY SURE OF, is totally wrong. Great article, very interesting. 

  10. Fantastic, now I can have something interesting to talk about in my Genetics class tomorrow morning.

  11. what_do_you_care says:

    Thanks for this. To me this is one of the many ways in which maleness is more tenuous than is rhetorically known or appreciated due to the non-gendered status of males for so long. While genetic arguments aren’t as easily introduced into rhetoric (though Latour is helping with that), the “surprise” of it is not so surprising.

    I catalog this along with a couple other “secret” factors that had lead to male dominance such as:

    The male need to identify progeny as their own (now irrelevant due to DNA testing) – leads to control of women, and property

    The male need to be fully aroused to reproduce (this is the irony of having to get convincingly excited or else die [generatively speaking], also increasingly irrelevant albeit less rapidly) – leads to rampantly reinforcing sexualized identities of women

    Who knows what else is out there?

    Btw, in case you are the macho police reading this, I’m a straight cis-gendered macho man that just happens to know things. As it turns out it knowing things doesn’t make you different from who you already are. Another surprise perhaps.

  12. Kimmo says:

    There’s nothing wrong with the term normal other than stupid positive connotations created by a culture that considered weird a perjorative.

    I’ve always disregarded those connotations like I disregard any conformist propaganda – don’t let a pack of small-minded fuckwits ruin a perfectly good word.

    There is no value judgment associated with proper use of it, and complaining about it in a scientific context, for crying out loud, is exactly the sort of crap that gave political correctness a bad name.

    Shame, Maggie, for apologising.

    • Antinous / Moderator says:

      You realize that people worldwide are being imprisoned, assaulted, tortured and murdered, sometimes by the medical profession, for being not normal?

      • Tess says:

        Yeah, I’m fine with using it in a statistical sense but otherwise, whether Kimmo there likes it or not, those connotations exist.  Normal equals good, right, fine, the way things ought to be.  Abnormal implies bad or wrong.  Individuals can choose to ignore those depths of meaning but they still exist. 

        I wish it was possible to wave a magic wand and have no one persecuted for reasons of abnormality – whatever abnormality that is.  Don’t live in that world now, though, and we don’t get to redefine the language willy-nilly.  The meaning attached to language is a shared thing.

        That said, I wouldn’t have corrected Maggie on the usage.  It wasn’t in a particularly awful context, in my opinion, and most other words would probably have seemed clunky or detracted from readability.  I suppose “unaltered” might have worked? 

        • Kimmo says:

          Yeah, I’m fine with using it in a statistical sense but otherwise, whether Kimmo there likes it or not, those connotations exist.  Normal equals good, right, fine, the way things ought to be.  Abnormal implies bad or wrong.  Individuals can choose to ignore those depths of meaning but they still exist. 

          IME, and this is an Australian experience, people who’ve used the term in that sense are generally stupid and/or religious. As far as I was aware, normal pretty much only equals those things as far as the feeble-minded are concerned.

          Of course, general usage is more likely to have been more thoroughly corrupted over the pond, where 1950s ‘educational films’ instructed youngsters in the dangers of non-conformism…

          I wish it was possible to wave a magic wand and have no one persecuted for reasons of abnormality – whatever abnormality that is.  Don’t live in that world now, though, and we don’t get to redefine the language willy-nilly.  The meaning attached to
          language is a shared thing. 

          We do get to redefine language – at least collectively. How else did we arrive at this position? I’m merely advocating correction. The time is ripe to grind those oppressive connotations into the dust.

      • Kimmo says:

        Sure I do. But that diminishes my point not a jot. Maggie didn’t misuse the term, or contribute in any meaningful way to the persecution of the abnormal, so why should she apologise?

        Normal still means normal, and nothing else. To say someone (let alone a bloody mouse, FFS) isn’t normal isn’t an insult, it’s (hopefully) a statement of fact.

        If someone’s stabbed, do you imprison the sociopath, or ban knives?

        Instead of moaning about statistical realities, maybe we’d be better off directing our attention to actual problems like those you mention… then we won’t have to tread on eggshells around those who’d have us tearing pages out of the dictionary.

        • Well, for starters, you’re already perpetuating a callous and inaccurate stereotype that conflates sociopaths with murderous impulses, so I’m inclined to believe maybe you do need a good long discussion about the more *subtle* forms of discrimination against the “abnormal” after all.

          FWIW, I’m not a sociopath myself, but I’ve had people in my circle of friends afflicted with it who were good people honest people, trying to deal with both their impairment and the damaged caused by people’s prejudice. And I think that might be a fine example of an “actual problem.”

          (I’m still inclined to agree with you that Maggie committed no great sin.)

        • LaGrange says:

          If someone’s stabbed, do you imprison the sociopath, or ban knives?

          Your analogy would be valid if 90% of knives were used to stab people, and yeah, in that case, ban knives. Also never mind, by that point civilization is dead anyway. Thankfully, right now most knives appear to be used to slice bread.

          Less thankfully, the word “normal” is used, most of the time, to separate the “okay” people from the “not okay” people. 

          We do get to redefine language — at least collectively.

          Unless there’s 3.5 billion of you, no you don’t.

  13. SomeGuyNamedMark says:

    Gender is a survival strategy eukaryotic species (multicellular colonies of them in our case) developed in the precambrian period as a way to combat bacteria, parasites, viruses and the environment.  There is also the benefit of DNA and mitochondrial refreshing.  We made up the rest.  That’s all.

    • Tess says:

      Gender is a survival strategy eukaryotic species (multicellular colonies of them in our case) developed in the precambrian period as a way to combat bacteria, parasites, viruses and the environment.  There is also the benefit of DNA and mitochondrial refreshing.  We made up the rest.  That’s all. 

      Nah, dude, that’s sex.  Or, more accurately, that’s sexual reproduction.  We could totally have sexual reproduction without having what we think of as biological sexes, or with more than two.  Or whatever – we could be like the people of Winter and go into kemmer once in a while.  We could also have sexual reproduction without gender.  I’m a huge fan of the ability of many species to mix the genes up in hopes of coming up with something better, I really am, but that’s not the same thing as gender.  Or even sex. 

  14. dafyvr says:

    Many years ago the New York Academy of Sciences published a magazine called The Sciences. One issue had an article on the number of possible genders. Nine, if I recall correctly. Every so often I kick myself for not keeping every copy of that magazine, and that issue in particular.

    Maggie, thanks for reminding me of that.

  15. valeriekeefe says:

    It’s a shame that Zarkower doesn’t realize that about half of trans women (Your mileage may vary) would be very happy with a pair of external ovaries. Not every woman needs or wants a vagina, and if you don’t believe me, I have some cis female-identified friends who would love for phalloplasty to be affordable and available to women without having to take testosterone to show you.

  16. awjt says:

    Normal carries so many conformist ideologies with it.  And so do outliers. But outliers often say just as much about the data as all the normal values do.

  17. Lobster says:

    Interesting article.

    *crosses legs, folds hands over crotch*

  18. Kimmo says:

    Lots of people have murderous impulses, I bet (I’m not one of them)… far fewer actually act on them.

    I’d say being able to be willing to take another’s life is a fairly sociopathic headspace by definition, but then I’m no psychologist.

    But speaking of conflation, I hardly implied all sociopaths are murderous, did I? I merely implied all murderers were sociopaths.

    Which from a certain angle (obviously not a clinical one) seems pretty valid to me. If you can walk around killing people, there’s some sort of pathology in your socialisation, no?

    It’s basic etymology. Which is pretty much the crux of this digression. Surely people have the right to employ words in their most ovbious sense without people coming from whatever angle demanding their own special case be reflected in everybody’s general terms.

    Everybody’s normal in some ways and abnormal in others. Different modes of abnormality are intrinsically associated with varying degrees of inconvenience, mitigated only by society’s willingness to go out of its way to accomodate it. I know about that; I had to watch a large amount of my potential glacially pissed away over thirteen years by an education childminding system that did absolutely nothing to accommodate any intelligence a couple of SDs above the mean. And society stands a lot more to gain by doing something about that issue than redefining words, I’ll hazard.

    If you’re in a position where you find the general use of certain words harmful, by all means attempt to introduce a new word; I have no problem with that. But you better have a damn fine reason if you want to make any of the old words verboten.

  19. Marko Raos says:

    Jeez, giving negative connotations to the word “normal”… how touchy can you get?
    There are such things as “normal homosexuals,” “normal heterosexuals,” “normal hipsters,” and “normal penguins.”
    “Normal” means conforming to the norm of a given group (or class, what have you.) Nothing more or nothing less.
    In some things I’m “normal” in others I’m “abnormal” for the categories I can be said to belong to. I can’t see anything wrong with this label unless it is used as a way to repress groups or individuals. In fact, there are groups where being labeled “abnormal” in the context of the society as a whole ensures your “normality” within the group.
    Just because some morons abuse a perfectly normal (heh) and useful word is no reason for banning or vilifying it. An idiot can destroy pretty much any idea. Hitler used Darwin’s theory of evolution to justify mass murder of congenitally ill as well as elderly AND homosexuals. Is that the reason to ban the theory of evolution? Please, politically correct people, don’t play into the idiots hands.
    Great article, btw.

  20. Ant says:

    I thought all chickens were females before becoming hens.

  21. Tom Finland says:

    Yep, I found the word “normal” a bit off-putting. But this doesn’t make me some overly-sensitive person who imposes political correctness on others, nor does it make me an out-and-out assimilationist (nor feeble-minded, nor religious…). But I am a transgender man who has, like many people, been on the wrong end of normative ideas of gender. Such norms wield immense social and cultural influence (e.g. they’re influential enough that, even just in Maggie’s case, she found it difficult to avoid using the word “normal” in writing this article). Given this influence, unsurprisingly, I did find the use of “normal” a bit off-putting (although I was aware of Maggie’s good intentions in writing the piece).
     
    I’m all for attempting to revise opinions around the word “normal” but this doesn’t mean we should devalue valid emotional reactions to widely-held ideas around what’s considered “normal”. And, really, if you want to attempt to reclaim the word “normal”, it would seem important to consider these very sorts of burdens that norms place on people. Considering this doesn’t require excessive political correctness… but, hey, a little sensitivity goes a long way. 

    PS Maggie – thanks for your kind and reasonable reply.

Leave a Reply