I want to rescue this from my account on the birdsite but I once got into arguing with TERFs (it happens, try not to judge me too harshly) and as a biologist I just wanted to push back a little on the "it's just biology" line, so I wrote the following:
Okay, sex determination in humans.
This shit is COMPLICATED and this will probably be a longish thread. Sorry. But I've seen a lot of people claim that "biology says" that everyone is either male or female, full stop, and it's just not true. 1/22
So human fertilized eggs develop into embryos with a pair of "indeterminate gonads" and TWO full sets of tubes. The Wolffian ducts can develop into the epididymis (omg spelled FROM MEMORY) & vas deferens, and the Müllerian ducts can develop into uterus and fallopian tubes. 2/22
Most embryos that get a Y chromosome will have a working copy of a gene called SRY (for Sex-determining Region on the Y). The product of the SRY gene is a protein that can control when other genes are turned on. If the cells of a gonad start making working SRY protein … 3/22
… then they start to develop into a testis. Some of those cells produce high levels of testosterone, and some make a protein called Müllerian-Inhibiting Substance. The Wolffian ducts need high testosterone to survive and develop; Müllerian ducts do by default UNLESS … 4/22
… MIS is around to stop them. So SRY can coordinate a program that shunts the default female development into male development.
Chromosomes can break and pieces can rearrange, so some people get a Y chromosome without an SRY gene, and are usually seen as female at birth. 5/22
Humans didn't evolve to have Y chromosomes in the females, or only 1 X, so these people generally have abnormal sexual development and tend not to be fertile. Likewise, the rearrangement can mean that SRY winds up on another chromosome, so someone can be XX and "male." 6/22
Without some other genes on the Y chromosome, and with 2 Xs, these people do not exactly develop the "normal" male program.
But it's a LOT more complicated that that, even. 7/22
I was careful to say "a working copy" of SRY above, because genes mutate sometimes. A change of a single DNA "letter" (out of >800) can make a completely broken protein that's like not having an SRY gene at all. OR, it can make a partially changed protein. 8/22
SRY controls a lot of things, so a partial change in the protein can mean activation of some crazy subset of the genetic program it normally activates. The result is an embryo not really developing as male, exactly, or as female, exactly. 9/22
Consider, too, that the enzymes that make testosterone are made from genes (controlled by SRY) different from the gene for MIS. One of those and not the other can be broken, and you can develop with unusual combinations of Wollfian/Müllerian duct products. 10/22
And just like SRY, the enzymes that make testosterone can be partially changed, and you can make intermediate levels, that don't exactly direct male development but don't exactly direct female development either. 11/22
For other parts of the body to become "male" or "female," they have to respond to these signals. That early embryo has tissues that can either become a penis and scrotum or a clitoris and labia. Mostly the difference is in how much testosterone they see. 12/22
But responding to it requires another protein that controls other genes, this one called the Androgen Receptor. People with AR mutations can be XY with a working SRY gene, but will generally be viewed as female because their cells don't know that testosterone is high. 13/22
At puberty, lots of other cells become responsive to these signals. Breasts and beards may develop. When different cells in an animal all turn on a gene, it's often the case that different DNA sequences near that gene control that process in different cells. 14/22
(These sequences, called "enhancers" and "silencers," are what I actually work on myself.) Just like the parts of genes that make proteins, these can be different between people, so the subprograms that make up the broader genetic program of sex can differ. 15/22
Most complex and controversial of all of this, it is *likely* the case that part of this program happens in the brain.
No one really knows what "masculinization" or "feminization" of a human brain means! (Though very smart people are earnestly trying to figure it out.) 16/22
@stevegis_ssg Yes, there is a model called "four core genotypes" in mice where the gonadal sex is not correlated with the genetic sex (XX with testes and XY with ovaries) to study whether behaviors are dicted by the sex chromosomes or the gonadal hormones. However, to make XY females we mutate Sry, but we know Sry is also expressed in the brain. As such the model is imperfect. People currently work on a better model 👌
Steve Gisselbrecht
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