Sex Determination

With a stroke of his magic Sharpie, Donald Trump tried to change biology on the first day of his second presidency.

He signed an executive order that the federal government will henceforth recognize only two sexes – male and female. The order then defined “female” as a person who at conception belongs to the sex that produces the large reproductive cell, and “male” as a person who at conception belongs to the sex that produces the small reproductive cell.

Whoever drafted this order was not a reproductive biologist (but they did get the relative sizes of the egg and sperm correct). The phrase “at conception” was no doubt inserted to further their anti-abortion agenda but has an unintentional humorous effect. All fetuses are female for the first 6 weeks of life before the presence of the SRY gene starts turning some into males. So according to this executive order all Americans must be female.

Trump also signed a flurry of other orders attacking the LGBTQ+ population of Americans, based on the belief that sex is binary. But is it always? Let’s take a closer look at the biology of sex determination.

First I’ll define some terms as I use them here.

Sex has to do with a) the primary or reproductive sexual traits – presence of ovaries or testes, and b) the external genitalia – uterus, labia, vagina and clitoris or scrotum, prostate and penis.

Gender is an expression of social and sexual identity in human cultures [Chakrabarty]

Sexual orientation is the physical, mental, emotional or sexual attraction to a particular sex [Wikipedia].

Intersex – having a combination of female and male sexual traits

Chakrabarty puts it this way: “Sex is in your pants; gender is in your head.”

Here are two quotes from Carole Hooven’s book T:

In humans, sex is usually determined at conception based on whether the sperm has an X or Y chromosome.

An individual’s sex isn’t always consistent with its sex chromosomes. What matters most is the particular pattern of gene expressions that leads to the development of testes or ovaries.

There are three main stages of sex development.

1.      Conception – chromosomes

2.      Fetal – development of sex glands and sexual anatomy

3.      Puberty – development of secondary sexual traits

Changes can occur at any of these stages preventing the pure development of one sex or the other. The general term for these is Disorders of Sexual Development or DSDs. The chart here shows the complexity of gender development and DSDs.

Typically, an individual with two X chromosomes will develop into a female; an individual with an X and a Y chromosome will develop into a male. But there are exceptions.

The critical part of the Y chromosome is a gene called SRY. In rare cases during meiosis the gene may migrate onto the X chromosome in either the egg or sperm. Without the activation of the SRY gene, the fetus will continue as female, therefore an XY individual without the SRY gene can develop into a female and an XX individual with one can develop into a male. Whether you identify as a man or woman, you have no way of telling which sex chromosomes you have without doing a DNA test.

One DSD in which a genotypic male (with XY chromosomes) develops into a phenotypic female is Complete Androgen Insensitivity Syndrome (CAIS). The fetus develops testes which produce testosterone but the testosterone receptors don’t work, resulting in a phenotypic female. More on this disorder later.

By the sixth week in a developing fetus, a cluster of cells has formed on each kidney that will develop into the sex glands. At this point they could become either ovaries or testes. That is why Trump’s definition of sex at conception was mocked – we are all female at conception. What triggers the differentiation in the gland development is the presence of the SRY gene (which as I have shown is usually but not always on the Y chromosome). The SRY gene creates SRY protein which turns on and upregulates (increases the activity of) another gene called SOX9 on Chromosome 17. The SOX9 gene creates SOX9 protein which in turn upregulates a number of other genes which cause the cell cluster to develop into testes. Without the SRY gene the cells will develop into ovaries; the default sex is female. If the SOX9 or other genes in the testes-making pathway don’t function normally the fetus will likely develop into a female but with some male traits.

Two weeks later at 8 weeks the internal sexual organs differentiate. By this time the fetus has developed two sets of primordial ducts: Wolffian ducts and Mullerian ducts. The Wolffian ducts will develop into the male internal plumbing – the epididymis, the vas deferens and the seminal vesicles. The Mullerian duct will develop into the uterus, fallopian tubes and cervix. Only one set of ducts will develop, the other will degenerate. Which one wins the contest depends on the presence of testes. The testes produce two different hormonal signals – the Mullerian inhibiting hormone to cause the Mullerian duct to degenerate, and testosterone which causes the Wolffian duct to develop. Without the signals from the testes the Wolffian duct will degenerate and the Mullerian duct will develop – here again female is the default.

At 9 weeks the external sexual organs differentiate. In the absence of testosterone, or testosterone receptors, the genital tubercle and folds develop into the clitoris and labia. In the presence of testosterone, the same genital tubercle and folds develop into the penis and scrotum. Much later, in the third trimester, the testicles descend from near the kidneys into the scrotum.

In the case of CAIS where the testosterone receptors don’t function, but the Mullerian inhibiting hormone does, both the Wolffian and Mullerian ducts will degenerate leaving them with no scrotum, no uterus, and a “blind” vagina. Their testes will remain hidden in their abdomen, undescended. Most people with CAIS grow up as a girl and don’t realize they are different until they fail to begin menstruating. They go through adolescence much the same as other girls, developing breasts and hips, because enzymes convert the testosterone their testes produce into estrogen. They live a fairly normal life and often marry but of course can’t get pregnant with no uterus or ovaries.

Androgen inhibition isn’t always complete. Partial inhibition, called PAIS results in a combination of male and female characteristics to varying degrees. Such people are described as intersex.

A different example of DSD that shows up at puberty is often called Guevedoces, Spanish for “testicles at twelve”. With this condition a genotypic male (with XY chromosomes) is deficient in the enzyme 5a-reductase which is required for the conversion of testosterone to dihydrotestosterone (DHT). DHT is necessary for fetal development of primary sex organs so the child will appear female. At puberty increased testosterone production promotes secondary male sex characteristics (deeper voice, muscle growth, facial hair) and belated development and growth of male genitalia, turning girls into boys.

There are many more Disorders of Sexual Development – see the above chart. DSDs can occur at the chromosome level at conception; at the differentiation of the sex glands and the development of internal and external sex organs at the fetal stage; and at the development of secondary sex traits at puberty.

So sex isn’t so binary after all.

A recent survey found that about 7.1% of Americans self-identify as gay, lesbian, bisexual or trans. This is a small but significant population of America, amounting to about 24 million people.  It is estimated that around 2% of the population (about the same percentage as redheads) are intersex, although many are not aware of it. While some intersex people cannot have children, others can.

Donald Trump is telling these people that they don’t exist.

 

Sources

T – the Story of Testosterone, the Hormone that Dominates and Divides Us. Carole Hooven, 2021.

Explaining Life Through Evolution, Prosanta Chakrabarty, 2023

A simiilar post by my brother in November 2024

https://dablogfodder.blogspot.com/2024/11/transforming-identity-bigotrys-war.html