Thread by @enn_nafnlaus

Since Elon went and stirred up a hornet's nest by sharing a tweet that (falsely) implied that clinics give hormones to 4-year-olds, I think it's time for a biology thread on what *sex* (let alone gender) actually *is*. Beginning from fetal development.

https://twitter.com/marc_benton/status/1571884298839683073

It should go without saying, though apparently needs to be reiterated, that humans are all the same species. Indeed, while it's often said that it's "chromosomes" that define sex, this is not entirely accurate either - the difference comes down to just a handful of genes.

Up until about six weeks into development, male and female embryos develop identically. However, the presence [or absence] of a gene cluster called "SRY" (Sex Region Y) initiates [or not] a virilization cascade.

That's the tiny blue line on this Y chromosome.

Less than 1000 base pairs, this tiny region is key to starting [or not] the cascade. It's also highly evolutionarily mutable, varying greatly between species. This leaves it not only vulnerable to "breaking", but also to occasional transfer between X and Y.

So why don't these transfers (which create full cross-sex phenotype) persist in the population? The short of it is "infertility". XX males lack the needed azoospermia factor in the Y's long arm. XY females (Swyer Syndrome) have underdeveloped ("streak") gonads.

Otherwise they're generally phenotypically normal for a single sex and may not suspect anything until investigating a lack of fertility (or in the case of XY women, a lack of puberty due to the nonfunctional streak gonads).

Back to normal development. Up to the start of the virilization cascade, all fetuses are structurally identical. Key organs include the urogenital sinus, the paramesonephric (Müllerian) ducts, & the mesonephric (Wolffian) duct- to form common, female, & male organs, respectively.

The paramesonephric (Müllerian) ducts, in the presence of anti-Müllerian hormone (AMH) (and lacking "problems" - more later) degenerate into small vestigial tissues. Barring it, they develop into the uterus, fallopean tubes, cervix and upper 1/3rd of the vagina.

The mesonephric (Wolffian) duct does the inverse, developing in the presence of testosterone (becoming the epididymis, vas deferens, & the seminal vesicle), and degenerating in their absence.

Note: different hormone (AMH vs. testosterone). More later.

Most external genitals however form from the common urogenital sinus, and thus come in pairs from the same origin: labia-scrotum, clitoris-glans, prostate/paraurethral glands (as well as the lower 2/3rds of the vagina).

There is a smooth linear interpolation between the two.

To reiterate, the pairs *are* the same organ, just grown to different sizes/shapes. A glans IS a large clitoris. The scrotum IS fused labia. Etc. Prenatal hormone exposure changed their shape but not the nature of their existence.

To those paying attention, there's lots of places accumulating where things can go wrong.

* Defective SRY
* Transferred SRY
* Unusual karyotypes
* Presence / absense of AMH without absence / presence of testosterone
* Insensitivity to AMH or testosterone.

And so on.

Using a very broad definition of "intersex" (including e.g. Kleinfelter syndrome - XXY), up to 1,7% of the population deviates from the normal development process. For visibly ambiguous genital phenotype, it's 1 in 5500.

A couple examples:

1) Androgen Insensitivity Syndrome (AIS): a largely (PAIS) or completely (CAIS) phenotypically female, but XY. Generally infertile. They're exposed to androgens in the womb but do not react sufficiently (or at all) to them. Generally identify as female.

2) 5-alpha reductase 2 deficiency: XY, but body does not produce much/any 5αR2D, which converts testosterone to the more potent DHT. Born largely phenotypically female, but at puberty the testes descend, the voice deepens, the clitoris enlarges, & they undergo a normal male...

...puberty - leading to the nickname in the Dominican Republic (where it is most common) of "güevedoces" – "balls at twelve". Despite being raised female, they generally identify as male, and with medical assistance can sometimes father children.

The phenotype at birth provides what is known as "primary sex characteristics". Atop this," secondary sex characteristics develop" at puberty, due to the impacts of whatever hormones they are exposed to (e.g. regardless of genotype), and of course, from the same shared tissues.

Some of the older people among you may remember a joke in the 2000 movie "Meet The Parents" where Grey, trying to impress his would-be father-in-law describes milking a cat, and says anything with nipples can be milked. To which the father-in-law replies:

Except the answer to that is, "yes". "Male nipples" are not atavisms; they're undeveloped base tissue, never exposed to estrogen. Expose his breasts to the estrogen his body never encountered to develop the tissue, then to prolactin, and they will lactate. Exact same organ.

But if so much of the difference between male and female bodies is just mapped pairs, determining what they are by what hormones they're exposed to, then how does "transgender surgery" even come into the picture? Well, the short of it is: humans are not clownfish.

An animal evolved for midlife transitions between sexes needs complex *reversible* pathways, but ones not adapted for that only need *irreversible* pathways. While some human changes (such as fat distribution or skin properties) are fully reversible, most are not.

The presence of hormones never-before-encountered thus can trigger the start of cascades that did not go off previously (for example, breast growth, voice deepening, hair growth) but not reverse them if they have already occurred.

Capacity for response can also be altered by past hormone exposure. For example, a transman on testosterone will experience the clitoris developing into a micropenis glans, but will not reach the size of a man born that way. Timing affects potential.

Since pubertal impacts are mostly irreversible, and gender identity changes after the onset of puberty are quite rare, normally puberty blockers (GnRH agonists) are sometimes provided to delay any decisions until trans youth are older. When ceased, puberty starts as normal.

GnRH agonists have long been given to non-trans children who experience precocious puberty to delay it to a normal time. They temporarily block the receptor for GnRH, the hormone that triggers sex hormone production. Side effects are generally simply those of low sex hormones.

In the mid-teens, usually around age 16 or so, teens with persistent gender dysphoria may begin taking hormones, starting a late puberty. Unlike hormone blockers, changes from hormones can be permanent, but take time to accumulate.

For changes that cannot be reversed, surgery is an option (only to adults, and not all choose it). Much of this is just remapping identical tissues (glans/clitoris, scrotum/labia, etc). However, where tissue growth is insufficient or atrophy of the mapping organ occurred,

...grafts are required. Note that this also applies to intersex individuals who - as adults - seek surgical treatments.

To sum up sex:
* We are one species
* An amazingly small difference in gene expression triggers the sex cascade
* The sex cascade diverts from the binary...

plenty on its own
* Untriggered cascade events can be triggered later with hormones.
* Irreversible cascade elements require surgery - simple remapping when dealing with analogues, grafts otherwise.

One final topic is worth discussion: sex vs. gender.

As we all know, when we meet someone for the first time, the first thing we do is karyotype them, then do a blood test of their hormone levels, and lastly a genital check, before deciding what pronouns to use with them and how to interact, right?

In terms of social reactions, we respond to the reality in which the person *lives* - their appearance, their behavior, etc. The nature of their genitals come into play in few situations, and their chromosomes, in virtually no situations.

If you encountered these women with AIS, who were born phenotypically female, raised female, and lived their whole lives as female, are you going to call them "sir" and demand they go to a men's restroom because they're XY? Of course not. Their chromosomes are irrelevant.

While sex - whether you're talking chromosomal, hormonal, or phenotypic, which do not necessarily match - involves physical measurements, gender defines how a person interacts with the world - how they present / act, and are treated in response. The day-to-day.

Now, one certainly can choose to misgender someone - to take the unambiguous social gender of the individual, presented and lived - but refer to and treat them as the opposite gender because of "hidden" knowledge about certain sex characteristics.

But the question is: WHY?

I know a guy named Elim. Real name John Henry. Hates the name, goes by Elim. Do I interact with him, "NO! I have knowledge that your legal name is not Elim, it's JOHN HENRY! You're JOHN HENRY! Stop pretending!"

No. Because I'm not an asshole. And because *it doesn't matter*.

If one wants to go off on some campaign about the "realities of sex", the short of it for trans people is, "it's complicated, and their bodies lie somewhere on a continuum, how far depending on a wide range of factors, but up to "pretty close to normal" for matching their gender.

Aka: if someone melted down a crowbar and forged it into a sword, don't insist to me that it's still a crowbar just because the smith wasn't able to get rid of 100% of the crowbar's original crystal grain structure.

It's a friggin' sword.

But whether it is or not, that has nothing to do with whether you should treat a human being with basic respect rather than using hidden knowledge about ***their very existence*** for politically motivated target practice.

Anyway, end of thread.

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