There Are More Than Two Human Sexes

https://www.youtube.com/watch?v=kT0HJkr1jj4

In high school biology, we usually learn that the sexes in humans are fixed and concrete.
Whether you’re male or female is black-and-white and rooted in you DNA: your 23 rd pair of
chromosomes is either two X chromosomes or an X and a Y. That’s it. End of story. And that’s
essentially what scientists thought too. But it turns out that sex isn’t that straightforward. In
fact, biologists today are saying sex is a spectrum, and the scientific community is still working
on understanding and respecting the people who fall in the middle of that spectrum. To get this
out of the way right up front: we’re not talking about gender or sexuality here. Gender refers to
__social____ and __culture___ attributes and understandings of men and women and their
roles, though not every culture has only two categories, and it’s increasingly seen as a
spectrum. Plus, the gender you identify as may or may not be the same as what you express
with things like your clothing and behaviour, all of which can also be on a spectrum.
__sexuality___ describes who you are attracted to, and it can be equally complicated and on a
spectrum. Where you are on these spectrums isn’t necessarily fixed!
But what we are talking about today is your biology, including your chromosomes, your
hormones, your gonads, and your genitals. The catch is that these biological features don’t
always agree with each other. And they certainly don’t always conform to those high school
health class diagrams that tell us there is a single, universally correct pathway to being male or
female. In fact, it’s estimated that nearly 2% of live births are born with __congenital____
conditions of atypical sex development. That basically means that something in their
chromosomes, hormones, gonads, or genitals is different from what many people expect of a
“boy” or a “girl”. This used to be known as being intersex, but these days, it’s better described
as having ___Difference of sexual Development___, or DSDs. While nearly 2% might not sound
like a lot, it means there could be 130 million people or more with DSDs. If all those people
were in one country, it’d be among the top ten most populous countries in the world. Plus,
DSDs are not always something you can see. People can spend their whole lives thinking they’re
one sex based on anatomy, only to find at least part of them tells a different story. You see,
your sex is the result of both ___sexual determination__ and _sexual differentiation______.
Sexual determination has to do with what chromosomes you get. Those largely
determine what happens to your body during sexual differentiation – the process by which you
develop the __physiological characteristics___ associated with your sex. Contrary to what you
might think that differentiation doesn’t stop when you’re born – it continues throughout your
life. That means that there are a lot of moments where differences between people can happen
– so of course, there are a ton of different outcomes! We tend to put these outcomes into two
boxes based on visible anatomy, or what scientists call __phenotypes___. Phenotypical males
have testicles and a penis, while phenotypical females have ovaries, a uterus, a vagina, and
vulva. But in reality, none of the traits we use to discriminate between the sexes are truly
binary. There’s a lot of variation within what we call male or female, and there’s a lot of overlap
that’s normal, too. Anatomically, someone might look phenotypically female on the outside but
not have ovaries or a uterus or have tissue from both ovaries and testes. Genetics aren’t any
clearer, because when it comes to chromosomes, people don’t always just get two Xs or an X
and a Y. Xs and Ys contain genes that help determine sex, with the Y chromosome conferring
the genes that enable you to develop male reproductive parts. But the processes for producing
sperm and eggs are really complicated, and they can lead to lots of different results. In this
process (abbreviated version), specialized cells basically duplicate themselves, then undergo
two rounds of division to produce reproductive cells, or gametes, that have half of the parent’s
genetic material. So, it makes one set of 23 chromosomes. But sometimes, the chromosomes
don’t split into exact sets of 23 – and that means there are a whole bunch of possible
combinations of Xs and Ys that a person can end up with. For instance, people can inherit three
Xs or an X and two Ys. These folks are normally taller than average. Those with three Xs have
slender builds, and sometimes have minor learning disorders. The people who have an X and
two Ys, on the other hand, tend to have more acne because of the extra testosterone in their
systems. In both cases, people retain full fertility. Then, there’s __turner syndrome_____, which
happens when you get just one X. That results in female characteristics, but the people who
have it tend to be shorter, don’t really go through puberty, may have mental disabilities, and
are sterile. ___Klinefelter syndrome, which results from two Xs and a Y, is the most common
chromosomal sex anomaly. It happens in one in 600 males births and can cause lower
__testosterone____ production and cause incomplete testicular development, though the
symptoms can be minor enough that a person isn’t diagnosed until later in life. Now there’s
also the fact that all your cells in your body don’t necessarily have the same chromosomal
makeup. Which like, what? Did I learn nothing but lies in high school? But it’s true – someone
with mosaicism can develop from a single fertilized egg, but have a patchwork of genetically
different cells. Someone who’s a genetic chimera has different cells because they develop from
two different fertilized eggs that merge in the womb. In both cases, it’s possible to end up with
a mix of cells with different sex chromosomes. And depending on the distribution of those cells,
mosaicism and chimerism can result in ambiguous sexual characteristics or both male and
female reproductive body parts. It’s even been shown that pregnant people and their fetuses
frequently swap stem cells through the placenta in a phenomenon known as
___microchimerism___. That means a chromosomal “female” can be carrying around XY cells,
and her son can have XX ones. In some studies, these cells have been shown to stick around in
the mother for several decades.
But all that said… there are also plenty of people with double-X or XY chromosomes that
also have differences of sexual development. That’s in part because at least __25__ genes play
a role in sex differentiation. So both ___mutations____ and __relocations___ of these genes
can result in a range of differences. Genes necessary for male development can be swapped
onto the X chromosome, for example, or someone can end up with multiple or mutated
versions of other sex-determining genes. Some of these are on other chromosomes and are
inherited as run-of-the-mill __recessive__ traits. All of these genes really start to be influential
around six weeks of development. You see, at six weeks, the fetus has a pair of bulges called
the __gonadal ridges____ next to its kidneys – and they have the potential to develop into
ovaries or testes. The fetus at this point also has two sets of __ducts___. One set can develop
into the uterus and fallopian tubes, while the other set has the potential to become the
epididymis, vas deferens, and seminal vesicles. What happens from there is somewhat of a
balancing act of different genes working in concert. Essentially, different networks of genes
shout MALE and FEMALE, and when that balance gets knocked slightly askew, it can move a
person along the sex spectrum. Take SRY, discovered in the 1990s. This is the male
programming gene, and it has a big effect on development. If it ends up on the chromosome of
someone who is XX, it can cause them to develop testes instead of ovaries. This can happen
because there’s a step in sperm and egg production when chromosomes swap some DNA with
their partner chromosomes. Even though the X and Y chromosomes generally don’t join in on
this DNA swapping process, they sometimes do. Plus, other mutations that occur during the
production of gametes can result in multiple or mutated versions of SRY or other sex-
determining genes because it’s not the only gene that matters. There are also other genes that
actively encourage the fetus to develop female characteristics. For instance, the gene
__WNT4__ suppresses testicular development and promotes ovarian development, and
multiple copies of it can cause incomplete female gonads to develop in people who are XY.
Gonad development also triggers the production of sex-specific hormones, which results in
further sex-specific development. But some people have differences of sex differentiation that
limit their ability to respond to those hormones. ___Complete Androgen Insensitivity ___
syndrome is one of these. People who have it are unaffected by male sex hormones, because
they have some kind of mutation to the protein that these hormones bind to, called the
Androgen Receptor. That means that while they have testes and a Y chromosome, their exterior
genitals appear female or in between. There’s also __Congenital Adrenal Hyperplasia_ , the
most common DSD out there. That’s when the adrenal glands underproduce cortisol and
overproduce androgens, the male hormone group that includes testosterone. The
underproduction of cortisol can lead to health problems, while the overproduction of
androgens can lead to external __male genitalia__ paired with internal ___female gonads___ in
people with XX chromosomes. Some of these conditions don’t fully present themselves until
puberty or later. In fact, some aren’t realized at all until a person seeks some kind of medical
care that reveals them. For instance, in 2014, doctors reported one case of a 70-year-old father
of four whose “hernia” turned out to be a uterus with fallopian tubes.
In many cases, differences in sexual development are notable from birth; for those
newborns, it may be possible to assign a gender based on what they are more likely to identify
as, as they grow up. The thing is, with all of the things that can happen during sexual
development, when a child is born with an obvious difference of sex development, it’s not
always clear why. Looking at chromosomes often isn’t enough, and sometimes a hormonal test
isn’t either. Even if the child’s doctors have a sense of what’s going on, determining what, if
any, treatment is necessary can be challenging. Back in the 1960s, it was thought that growing
up without clearly defined sexual organs would cause ___emotional trauma___. So, there was a
push towards performing surgery on infants to clearly assign them a sex. Due to social stigmas
surrounding DSDs, parents were often encouraged to keep all of this a secret, even from the
child. So people grew up without knowing kind of important details about their own bodies. It’s
hard to get numbers on how many of these surgeries were – or even are being – performed. It’s
also hard to know exactly how these surgeries affect patients, but as adults, many report pain,
scarring, and a loss of sensation. Also, people with DSDs do report high rates of ___gender
dysphoria__, where their chosen gender does not align with their assigned sex. There is also an
association between gender dysphoria and mental health issues, like self-harm behaviours, so
these surgeries may contribute to mental health problems later in life. Though, it’s important to
note that such issues are less likely if people have supportive and affirming parents who accept
them as they are. Sometimes, surgery is medically necessary, such as to unblock the urethra.
Also, surgery can help to __fertility___ or, in the case of complete androgen insensitivity
syndrome, to reduce the risk of ___testicular cancer____. But from a medical perspective,
those surgeries don’t need to be performed on infants. In fact, most of the time, differences in
genital anatomy at birth aren’t something that needs to be fixed. At least, not until the person
is old enough to make their own choices about what they want their bodies to look like.
Nowadays, healthcare is moving away from a surgical approach. If a DSD is identified at
birth, treatment is more likely to include therapy and ___hormonal replacement___than
surgery. Often, a DSD team is involved in care, which can include geneticists, endocrinologists,
and psychologists or psychiatrists. They help the family decide if any interventions are
immediately and medically necessary and help provide care and support to the child with DSD
and their family throughout childhood. Unfortunately, this kind of care still isn’t available
everywhere. For now, researchers are working to better understand the development of both
sex and gender over time, and to gain a clearer sense of when kids begin to understand their
own gender identity. The problem, of course, is the fact that from clothes to restrooms to
organized sports, they are raised in a society that is set up around a binary that just… isn’t
binary. But researchers are thinking about how we can make our overall discussions and
understanding of sex even more inclusive – and more accurate. Because even though biological
sex may seem like one of those things that is relatively straightforward in a very, very
complicated world. it’s not! While there’s probably still a long way to go to understand it, we
are making progress.