Transgender Visibility Day: What is Transgender?

Today is Transgender Visibility Day, March 31, 2024. It has occurred on March 31 since 2009.

In short, transgender (sexual dysphoria) occurs when external anatomy looks like one sex, and the brain structures associated with gender identity demonstrate patterning and function of the other sex.

Let’s shed some light on what transgender is, biologically.

Fetal development, simplified:

• Much of anatomical development, including both internal sex organs and external sexual anatomy, occurs during the first half of fetal development.
• Brain development of areas that differ from female to male develop during the second half of fetal development.
• Male patterning of both anatomy and brain structures occurs to the degree to which a fetus is exposed to male hormones at the time of their development.
• Absent male hormones, female patterning occurs.
• At about 6 weeks into an embryo’s growth, the SRY gene on the Y chromosome activates additional genes, which in concert produce male hormones and kickstart male development.
• Sexual differentiation is not driven directly by the presence or absence of a Y chromosome, but rather is driven by the hormones and proteins produced by the SRY and other genes that influence sexual development.

A consequence of this last bullet item is that endocrine disruptors that either mimic or disrupt sex hormones in the fetus can drive the sexual differentiation of organs and brain structures that are developing at that point in time. Disrupting factors can include:

• Endocrine disruptors present in environmental toxins, PFAS, phthalates such as those present in many plastics, DDT, PCBs, dioxins, etc.
• Prescription or other drugs taken by the pregnant mother, such as DES (diethylstilbestrol, a synthetic estrogen sometimes given to pregnant women), nicotine, amphetamines, and others.
• More than 2 sex chromosomes (XXY, XYY, XXXY and others), or, more rarely, only one X (XO, Turner syndrome).
• Congenital Adrenal Hyperplasia (CAH), aka Adrenogenital Syndrome
• Maternal stress

If the sum of hormones and disrupting factors to which a fetus is exposed differs in level from first to second half of development, then the physical anatomy can develop as one sex, and brain structures can develop as the other. Depending on timing, this can result in gender dysphoria – feeling transgender.

Brain structures associated with gender identity and sexual orientation, with the exception of the INAH-3, don’t all develop simultaneously. Those currently determined to be associated with gender identity:

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

Brain structures associated with sexual orientation:

• INAH-3
• SCN (suprachiasmatic nucleus)
• Anterior commissure

It should be emphasized that fetal sexual development, even within a particular phase, does not occur in a simple binary state like an on-off light switch. It begins at about 6 weeks in the embryo, and proceeds like a dimmer switch, sliding toward male to the degree to which male hormones and other factors, such as those above, push male development. From six weeks to birth, those hormones, endocrine disruptors, and other factors, can change and push that sliding switch back and forth to varying degrees. When somewhere toward the middle, whatever is developing at that time can be sexually vague, ambiguous, neutral, or bi.

External sexual anatomy, internal sex organs, brain structures associated with gender identity, and brain structures associated with sexual orientation develop in the fetus at different times, each on a sliding-scale, or continuum, resulting in a mosaic of sexual differentiation across those areas, and even within a specific structure, sex organ, or sexual anatomy. (In female-male differentiating brain structures, the difference is identifiable by structure size and/or its density of neurons.)

In short, transgender (sexual dysphoria) occurs when external anatomy looks like one sex, and the brain structures associated with gender identity demonstrate patterning and function of the other sex.