The complexity of defining someone’s “sex”

With so much trans vs anti-trans conversation of late, exhortations to “go with the genetics” or “go with the birth sex” are unfortunately off the mark. These folks likely aren’t intentionally incorrect, but rather just uninformed. Most of us were taught in school that a person will have two sex chromosomes, sex chromosomes being designated “X” or “Y”. We were taught that having two X chromosomes (XX) makes a person a woman, and that having one X and one Y (XY) makes a person a man.

The problem with that simple and binary summary is that it’s oversimplified, incomplete, and has led to shameful persecution of those who don’t fit into that incorrect and misleading coin-flip of a definition.

How do you define sex?

When thinking about how to identify someone’s sex, what do you think of first – sex chromosomes or “private parts”? By high school, we probably know that having two X sex chromosomes makes a person a woman, and an X and Y together make a person a man. A woman will have female external genitalia and accompanying internal sex organs. A man will have male genitalia and accompanying internal structures to aid in development of sperm.

The problem with this information is that it is oversimplified and incomplete. Not everyone has two sex chromosomes – some have more, and a few have only one.

We’re taught that male body parts produce male hormones (such as testosterone and other androgens) and that female body parts produce female hormones (such as progesterone and estrogen).

If you’re lucky, you also learned that males produce small amounts of female hormones, and females produce small amounts of male hormones. These low levels of opposite-sex hormones have been considered insubstantial in most discussions of male-female differentiation in the literature I have read. However, it’s likely that they play a role in the findings that it is extremely rare for the currently-known sexually differentiated structures of the brain to all follow either male patterning or female patterning – they almost always present a mosaic comprised of both.

Yes, there are structures within the brain that are sexually differentiated. Just by looking at those specific areas of the brain, a researcher can determine with 80% accuracy the sex of that individual. That said, a person’s sex isn’t really so easy to define, and that’s what you’re here to discover!

The genetics of sex

To start with, the genetics we’ve learned in school are incomplete. People have been found to have as many as five (and potentially more) sex chromosomes, and it’s possible for a female to have only one functioning X (designated XO). There are XXY, XYY, XXYY, XXXY, and so on. Having more than two sex chromosomes can not only make sexual development more complex, but can also affect broader development of the fetus.

Key things to remember about the genetics of sex:

• The presence of a Y chromosome is considered to define an individual as a genetic male.
• Absence of a Y chromosome is considered to define an individual as a genetic female.
• When multiple X chromosomes are present, only one of them is left fully activated in each cell of the body, and the one left activated can differ from cell to cell.

Think of a calico or tortoiseshell cat, which is a sex-linked female color pattern. If the orange fur color comes from the father’s X and the black fur color comes from the mother’s X, about half of the cells leave the mother’s X activated and produce black fur; the other half leave the father’s X activated and produce orange fur. The mix produces the calico (which includes base white areas) or tortoiseshell pattern.

Even this is oversimplified, as about 15% of the genes in each inactivated X chromosome remain active. Multiples of the same genes remaining active across multiple X chromosomes can produce too much of certain gene-related proteins and become problematic.

So far, we’re talking about genetic sex, not anatomy. Even basing genetic sex on the presence or absence of a Y chromosome isn’t always that straightforward.

What’s the deal with sex chromosomes?

It is an oversimplification to draw the conclusion that anyone possessing a Y chromosome will develop as a male, and that anyone not possessing a Y chromosome will develop as a female.

First of all, when only one intact X is present, or when an individual possesses more than two sex chromosomes, sexual development can become additionally complex. With more than two X chromosomes, some of the proteins associated with genes on the X chromosome will not be adequately suppressed via X-inactivation – but don’t worry about that detail; just be aware that additional sex chromosomes affect sexual development.

Various combinations of sex chromosomes and their effects have been well documented. One of the best free resources to learn about them is the website of the Association for X and Y Chromosome Variations (AXYS): https://genetic.org/. The site’s Variations tab is here: https://genetic.org/variations/. Several of these documented variations are listed with high-level overviews in the book Not a Choice: What you weren’t taught about the biology of sex and gender.

Sticking with the genetics, you may recall that about half the father’s sperm carry X chromosomes, and about half carry Y chromosomes; all of the mother’s eggs carry an X chromosome.

It’s the SRY gene on the Y chromosome that pushes fetal development on the male path. During sperm production in the father, it’s possible for the SRY gene to become translocated from its Y chromosome to an X chromosome.

If a sperm carrying the Y chromosome that is missing the SRY gene fertilizes an egg, the resulting fetus is genetically an XY male who lacks the gene that initiates male development, and may develop partial or complete female anatomy.

If the sperm carrying an X chromosome that picked up an SRY gene fertilizes an egg, the resulting genetic XX female fetus has picked up an SRY gene from her father’s Y chromosome, and may develop partial or complete male anatomy.

More information about how the SRY gene can become translocated from its Y chromosome to an X chromosome is provided in the author’s book Not a Choice: What you weren’t taught about the biology of sex and gender.

What’s magic about the SRY gene?

What’s the magic in the role of the SRY gene? It kickstarts production of androgens at about six weeks into the development of the embryo. These androgens push fetal development from female patterning into male patterning.

The SRY gene influences the SOX9 and other genes to bring about male development.

Beyond genetics

Sex chromosomes and their genes influence sexual development, including anatomy, sexual orientation, and gender identity, but there’s more to human sexual development than just genetics. There’s still room to sway fetal development in one direction or the other.

Certain conditions can vary the amounts of sex hormones that direct male or female patterns in the developing fetus. Exposure to drugs administered to the mother, endocrine disruptors in plastics and other products, environmental toxins, congenital adrenal hyperplasia (CAH), gene mutations (to SOX9 and other genes involved in sexual development), and other factors can vary the amounts of sex hormones or chemicals mimicking them that direct sexual development of the fetus. Certain gene mutations affect production of proteins or function of the endocrine system. Any of these influencing factors can vary over the nine months in which a fetus develops.

Fetal development

Key points to consider regarding fetal development:

• Greater exposure to androgens or chemicals that mimic them pushes development toward male patterning in the anatomy or brain structures developing at that moment in time.
• Sexual anatomy of the fetus develops during the first half of pregnancy.
• Sexually-differentiating structures in the fetal brain develop during the second half of pregnancy.
• Sex hormones (or mimicking chemicals and other factors) to which the fetus is exposed can vary at different times throughout its development.
• Sexual differentiation of brain structures and sexual anatomy occur on a continuum, or spectrum; sexual development is not an either-or coin-flip. While most lean toward female patterning or male patterning, any of them may be ambiguous or a combination of the two.

Internal anatomy, external anatomy, and sexually differentiating brain structures all develop at different stages during pregnancy, and most develop independently of one another. Subject to different genetic, hormonal, drug, toxin, or chemical influences in varying amounts at different times, a door is opened to considerable variation on the continuum of sexual development.

Sexual differentiation in the brain

Certain areas within the brain have been found to differ between females and males. Differences are measurable in the size, density, and number of neurons, with specific structures being larger and denser in men and others larger and denser in women. Structural differences drive functional differences in these areas:

• Hypothalamus
• Hippocampus
• Amygdala
• Corpus callosum
• Cerebral cortex

A subset of these structures within and near the hypothalamus have been found to determine gender identity and sexual orientation. Gender identity is the feeling of maleness-femaleness, which occurs on a spectrum rather than as a female-or-male flip of a coin. Sexual orientation determines whether an individual is attracted to men, to women, to both, or to neither.

These brain structures, which are patterned in the womb and determine gender identity and sexual orientation, are set during fetal development. Exposure to sex hormones later in life does not alter their patterning. Each occurs on a spectrum of female-male development. An individual whose gender identity patterning occurs toward the central portion of the continuum may not feel strongly male or female. An individual whose brain structures associated with sexual orientation tend toward the middle of the spectrum may not feel strongly attracted to those of a particular sex, but rather feel ambiguous, attracted to both men and women, or to neither. With the exception of the INAH-3, the identified brain structures affecting gender identity and sexual orientation develop independently of one another.

Gender identity and the brain

Specific structures associated with gender identity:

• Central nucleus of the bed nucleus of the stria terminalis (BSTc)
• Interstitial nucleus of the anterior hypothalamus, subdivision 3 (INAH-3)
• Infundibulum nucleus

People feel male or female to the degree to which their BSTc, INAH-3, infundibulum nucleus, and potentially additional structures yet to be determined, develop on the female-male continuum.

Sexual orientation and the brain

Specific structures associated with sexual orientation:

• Suprachiasmatic nucleus (SCN)
• Interstitial nucleus of the anterior hypothalamus, subdivision 3 (INAH-3)
• Anterior commissure

People are attracted to men or women, to both, or to neither, to the degree to which their SCN, INAH-3, anterior commissure, and potentially additional structures yet to be determined, develop on the female-male continuum.

Then how do you determine sex?

Since internal sex organs, external genitalia, and the differentiating brain structures develop at different times and independently of one another, their hormone and chemical exposure may differ.

Therefore, the degree to which sexually-differentiating anatomy and brain structures develop toward a female or male pattern can differ from one another. These include:

• internal sex organs;
• external genitalia; and
• sexually-differentiating brain structures, including those that determine gender identity and sexual orientation

Development of each occurs on a continuum, or spectrum. This presents a mosaic of varying degrees of female and male patterning, both within the brain, and potentially in sexual anatomy.

Mixed and/or ambiguous genitalia is the most obvious representation of anatomical “intersex” development. However, the term “intersex” also may be used in the broader sense to include any non-binary sexual development, including homosexuality, bisexuality, gender dysphoria, and so on.

How does one determine sex, then? That’s a really good question, isn’t it? If so many factors – brain structures, internal anatomy, and external anatomy – all develop independently of one another, and each can vary according to different degrees of both internal and external factors, then sex really is a mosaic that creates a female-to-male spectrum. It’s not a binary coin-flip at all.

So, what’s the answer?

The point is that a person’s sex is much more difficult to define than we have been taught in school.

You can’t simply define sex by genetics, because a person with a Y chromosome, while genetically male, may to all appearances be a woman.

Similarly, a person with no Y chromosome, while genetically female, may to all appearances be a man.

A person’s internal sex organs may represent a different sex than their external genitalia, so you can’t simply judge by a person’s genitals. Besides, either may differ from the representation of their sex chromosomes.

Then there are the brain structures that tell a person what gender they are, which may differ from the internal organs, the external genitalia, or the sex chromosomes. The same holds true for brain structures associated with sexual orientation.

To top it all off, any of these potentially sex-determining factors can develop ambiguously, toward the middle of the female-male spectrum. And they may be inconsistent with one another.

In the context of providing legal and civil rights protections for everyone based on “sex”, it is impossible to select one single criterion to define a person’s sex. With near-infinite possibilities for sexual development, we need to protect everyone, and not allow anyone to be discriminated against, regardless of how their sexual mosaic has developed.

###

This content is available in ebook format on Amazon at https://www.amazon.com/dp/B0B3SM7GKW

We’re currently working on broader distribution and reducing the price from 99 cents to free.

Note: Terminology can be a moving target between what is socially acceptable and what may be considered offensive. Even some scientific terms in published articles have become considered pejorative. Since the author’s focus is biology rather than sociology, please notify the publisher here if something printed in the article is offensive to the LGBTQI community. Thank you.

Want to learn more?

You can browse more at https://notachoice.net and optionally sign up for a free pdf file of content from the website.

Check out Not a Choice: What you weren’t taught about the biology of sex and gender on Amazon at https://www.amazon.com/dp/B07XK8HKQT or at Barnes and Noble.

Or visit the publisher’s website at https://www.handselpublishers.ltd.

The extensive list of references for the material presented here is available on the website and in the Not a Choice book.