Sex Isn’t All About Chromosomes
People on all sides of the sex and gender debate are confused about sex chromosomes.

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Few people could have predicted that contemporary society would become embroiled in polarizing debates over basic biological concepts concerning sex. Are males and females real and natural categories, or are they social constructs? If sexes are real, do they conform to a binary or a spectrum? Somehow such inquiries have recently ignited fierce controversies, abruptly ending an age-old consensus. While these debates are almost entirely a result of new fashionable ideologies rooted in Queer Theory, a discipline that views categorization as inherently oppressive, confusion about the science of sex is not entirely relegated to one side of the political divide.
One of the most persistent and widespread misunderstanding of biological sex, especially among those rightfully striving to uphold the distinction between males and females as discrete categories, is the oversimplified belief that XX chromosomes unequivocally denote a female, and XY chromosomes is what it means to be male. The End. No ifs or buts.
This exact viewpoint was recently put forth in an article titled “Let’s talk about sex – accurately” by a retired medical professional who goes by the pseudonym “La Scapigliata” on Twitter. Despite the title of her article, she inaccurately posits the perplexing notion that individuals with complete female reproductive systems must be deemed male should they happen to possess a Y chromosome, and conversely, that individuals with complete male reproductive systems must be considered female should they happen to lack a Y chromosome.
While it is commendable that La Scapigliata recognizes the real harm in gender activists’ attempts to strip sex of all tangible meaning, it is crucial that the biological facts be correctly represented.
All biological systems have structure and function.¹ Eyes are specialized tissues that produce sight. Hearts are specialized tissues that pump blood. And the nervous system is a complex network of specialized cells that send and receive signals throughout the body. The same applies to the male and female sexes, which also have specific structures and a specific function. The male sex is the reproductive anatomy that produces sperm, and the female sex is the reproductive anatomy that produces eggs.² The development of all these systems is determined by genetics.
In embryonic development, genes orchestrate the progression of these systems towards their specific functions; this process extends to sexual development. For most mammals, the presence of the SRY gene on the Y chromosome governs male development.³ The SRY gene triggers a cascade of genetic events that differentiates the gonads into testes, the factories for sperm production. From there, the male internal and external genital systems develop. Therefore, barring genetic mutations, if an embryo is conceived with a Y chromosome, it develops as a male; no Y chromosome, it develops as a female.⁴
When it comes to defining sex, many people on all sides of the sex and gender debate mistakenly conflate chromosomes with sex. Some use chromosomes to argue that sex is not binary, and others use chromosomes to argue that sex is binary. But using chromosomes to argue either case results in absurd conclusions.
For example, some argue that sex is not binary because there are atypical sex chromosome combinations beyond XX and XY. They label people with atypical combinations like X, XXY, XYY, or XXX as neither male nor female. This argument, however, ignores the fact that despite these chromosomal irregularities, embryos still develop distinctly male or female systems built around either sperm or egg production. Here, an overemphasis on chromosomes obscures the primacy of structure and function.
On the other hand, others argue that sex IS binary because all embryos with a Y chromosome are male, and all embryos without a Y chromosome are female, no exceptions. In doing so, they mislabel individuals with certain genetic disorders, assigning them a sex contradictory to their clear physical development. This too is incorrect because embryos with fully developed male systems are labeled as female, and embryos with fully developed female systems are labeled as male. Like the first argument, this view also erroneously places chromosomes as the sole determiner, neglecting structure and function.
There are two primary reasons why the chromosomal definition of sex is flawed, which I will outline below.
First, many species do not have the X-Y chromosomal system, and yet males and females are still produced. Across the plant and animal kingdom, nature has evolved many mechanisms for developing individual organisms into males or females.⁵
For instance, birds use Z and W chromosomes, where the females develop with ZW and the males develop with ZZ.⁶ Reptiles, however, don’t have sex chromosomes and rely instead on environmental factors such as temperature for sex determination. A specific temperature range triggers male development, whereas a different range promotes female development.⁷
Evolution continues to refine these mechanisms, offering fascinating examples like the two species of rat that have lost their Y chromosome entirely. In these species, sex determination hinges on the dosage of a single gene, which directs embryonic development down either the male or female path.⁸
This diversity in sex determination mechanisms illuminates a key understanding: sex is not defined by chromosomes or the temperatures at which they develop. Instead, it is distinguished by the anatomical capacity to produce either sperm or eggs.
Second, genetic disorders can result in a sex opposite of what one would expect from the chromosomes. Three case studies help illustrate this fact:
1. XX male syndrome: This condition, occurring in 1 out of 20,000 births, produces males with XX chromosomes. It arises due to the translocation of the SRY gene (a male sex-determining region located on the Y chromosome) onto an X chromosome during cell division in the father's reproductive cells. The fetus, as a result, is conceived with an XX [SRY] chromosomal composition. The presence of SRY initiates a cascade of gene activation that prompts male development: the differentiation of gonads into testes followed by the formation of male internal and external genitalia.⁹
Despite their inability to produce mature sperm—a function that requires the AZF region from the Y chromosome—XX males are classified as male because they develop the phenotype associated with sperm production, a trait determined genetically. LaScap, however, argues that these unambiguous males must be considered females solely because of the absence of the Y chromosome. This ignores anatomy, physiology, and even genetics.
2. XXY SRY-negative female: This case involves a woman with XXY chromosomes who developed a complete female reproductive system, ovulated, gestated, and gave birth.¹⁰ At conception, the lack of an SRY gene on the Y chromosome and the presence of two X chromosomes allowed genes like WNT4 and RSPO1 to differentiate the gonads into ovaries.¹¹ The lack of testes and the subsequent lack of anti-Mullerian hormone and testicular testosterone then allowed for full development of female internal and external genitalia (oviducts, uterus, cervix, vagina, and vulva).
This woman is female, despite the presence of the Y chromosome, because she developed the phenotype that produces large gametes (determined by genetics). LaScap acknowledges this person has a “complete female phenotype” who is also “fertile as a female,” yet refers to her as a “biological male.”¹² This is a clear contradiction in terms.
3. XY CBX2 negative female: This case involves a girl with a normal female reproductive system (ovaries, Fallopian tubes, uterus, cervix, and vagina). Her case is unique in the medical literature because she has XY chromosomes with no mosaicism and an SRY gene! But why didn’t she develop as a male?
Clinicians discovered she was missing a gene known as CBX2, which suppresses ovarian development and helps SRY do its job.¹³ A mutation in this gene during the XY zygote stage incapacitates SRY, allowing for the development of ovaries instead of testes, and the formation of a female reproductive system: Fallopian tubes, cervix, uterus, and vagina. Despite the presence of a Y chromosome with an SRY gene, this girl is classified as female because she developed the phenotype associated with egg production, as determined genetically. This intriguing genetic phenomenon has been replicated in mouse studies.
As we can see from the cases above, claiming that Y = male and no Y = female, without exceptions, creates a host of logical absurdities. Consider this: if we categorize an XX male as female solely based on the absence of a Y chromosome, it would imply that some females possess testes, Wolffian structures, and a penis. If we define the pregnant XXY female or the XY female as males purely by the presence of the Y chromosome, one must conclude that some males can have ovaries, a uterus, cervix, vagina, and a vulva, produce eggs, and bear children.
In both scenarios, the reliance on chromosomes as the sole determinant of sex, ignoring the genetically determined phenotype related to gamete type, leads to illogical and contradictory conclusions. After all, how can a male develop a full female reproductive system and produce eggs? Likewise, how could a female develop a full male reproductive system and produce sperm? This is as paradoxical as saying that a piece of gold is iron and vice versa. However, gold is never iron and iron is never gold. Likewise, males can never produce eggs and give birth, and females can never produce sperm and impregnate. These reproductive capabilities are distinctly separate and exclusive to each sex.
The claim that chromosomes solely define biological sex is both misleading and has large and wide-ranging implications.
Activists who argue that males can be females and females can be males would love to use this reasoning to deconstruct the definition of sex for sociopolitical ends. Moreover, individuals with atypical development might find themselves inaccurately categorized: individuals with fully developed male bodies could be placed in female spaces and vice versa. This potential misclassification could profoundly affect medical treatment. For instance, a person with a fully developed female reproductive system might be inappropriately treated as a male by medical professionals, and the reverse could also occur. Such an oversimplified view, which reduces one’s sex to the mere presence or absence of a Y chromosome and ignores their structure and function, can cause critical sex-based differences in anatomy and physiology, determined by genetics, to be overlooked.
Because of this, it’s best we maintain the distinction between chromosomes and sex. Males and females are not defined as the presence or absence of the Y chromosome. Like all other biological systems, the sexes are defined by their structure and function: the reproductive anatomy that produces sperm or eggs.
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Thank you for this very informative essay. In principle, I agree with you. However, with all due respect, I think that many of the assertions are too simplistic (and some inaccurate) to move the conversation along. That's much of the problem with the ongoing debate. For instance, "eyes are specialized tissues that produce sight" is not sufficiently nuanced to make the point that sight is an emergent property of an intact functioning brain (eyes don't ''produce" sight). And, reptiles DO have sex chromosomes. Likewise, drawing analogies to the genetics of other animals is beside the point... even though I've been teaching biology and physiology for decades, I've always wondered how precisely to define the sex of the hydrozoan Obelia, but that has nothing to do with the sex of my children. Similarly, the two species of rat about which you wrote apparently have 10 genes that function in gonadal differentiation. They're just not on a 'Y' chromosome. I would also like to point out that the issue about aneuploidies has been discussed ad infinitum (even I put in my 2 cents)...
"If Aneuploidies = Sexes, Then Two-Headed Turtles Aren’t Turtles"
https://everythingisbiology.substack.com/p/if-aneuploidies-sexes-then-two-headed
...and simply reiterating these explanations will not change people's points of view. None of the broader arguments will ever resolve until people on both sides openly recognize the ambiguities of the edge cases, and there are some. That's just biology. As I tell my students, life is full ambiguities… get over it. However — and I want to make this quite clear, as I did in the article cited above — the ambiguities do not mean that the basic categories are illegitimate (Homo sapiens have two sexes). It just means there are rare ambiguities. So, in short, until the discussion becomes more nuanced and biologically accurate, it will simply remain an ongoing back-and-forth. Thank you again for this very interesting read. As I said, I do agree with you in principle. Sincerely Frederick
This is yet another unreasonably overly complicated view.
1) No one cares about other species. The debate about male and female is exclusively about human male and human female.
2) No one cares about the small number of exceptions. Yes, there are exceptions - but these are errors of development and construction. No one should confuse the categorization of male and female by these errors.
Chromosomes do set up the male and female categories.