Apparently, I have become a leading expert on human and sex development. Basically, I am a doctor that has spent a lot of time reviewing medical literature on physiology, genetics, development, psychiatry, neurology and speaking up. I can nerd talk about this stuff for hours. I've spent time studying various world cultures and history regarding intersex and transgender individuals. I work with both intersex and transgender individuals. I also collaborate with other doctors and research centers across the country and world. I have also worked with various government entities, large medical organizations, and religious entities. I would dare to venture "I've done my research" and "I know my s***."
In its simplest terms, biologic sex is more complicated than we give credit. Our current definition, as penned in Webster's dictionary, is woefully inadequate and part of the problem. I will slightly paraphrase, "of, or related to the sex that produces sperm or eggs." Obviously, male and female, respectively. According to most, those are two definitions, in reality, it is four. Those who produce sperm. Those who produce eggs. Those that produce neither and the rare occasion where someone can produce both. The "neither" is far more common than we think. That definition, BTW, is consistent across the English speaking world and other languages and cultures. Historically, however, the definition has evolved. There are various historical dictionaries online, but I ordered a few to watch the evolution of the definitions. My all time favorite was this definition of female, "not male."
When I ask medical students what the "of, or related to" means in those definitions I get blank stares. Most will say chromosomes. Others will say external anatomy. We divide sex biologic sex based on primary and secondary attributes. The primary attributes are identified as gametes, gonads, internal anatomy, external anatomy, genetics (not just chromosomes), hormones, the adrenal gland, and the pituitary gland. Eight characteristics that must work together to make the "of, or related to." The secondary characteristics develop as a consequence of the primary. These are the attributes we see from day to day and are the consequence of puberty. These include face structure, body fat composition, breast growth, hair distribution, skeletal growth and so on. Each one of the above characteristics have an infinite number of variations. It's not just the sequences of DNA or genes, we now look at the function and development of those genes over time. Called epigenetics.
To help put this in perspective, we can look at genetics as layers:
1) The chromosomal layer - this is where most people's education lies. They think simple Mendelian genetics and is frequently where they make their arguments
2) the gene layer - this layer has been developing since about 1995, but the first gene sequencers came about in the 1980s and were ridiculously slow.
3) the epigenetic layer - this is a new scientific research focus that has evolved from about the 2010s. This layer studies are the genes behave over time and includes concepts like "imprinting"
4) the phenotypic layer - this is what is the effect of the above
This is just looking at the body development and status. The brain develops semi-independently of gonadal development. The genes involved in brain development are different than gonadal development. There is communication between the two with hormonal signals and cell-to-cell communication, but they are otherwise independent.
In utero, a fetus has both male and female structures at the gonadal ridge. The mesonephros and paramesonephros ducts. (Wolffian and Mullerian ducts or typically male and female development pathways, respectively). In reality, both males and females have remnant structures of these processes. For males, they have the remnant "female" structure, the appendix testes and for females, they have the Gartner ducts. Genetic pathways of human development requires advancing the expected biologic sex and suppression of the alternate. Since, there are 100s of genes involved, the process can and does go awry of what is expected. This is where we get intersex conditions or variations of sexual development. This is also where and why we get individuals with gender dysphoria and are transgender.
Want a cool example of genetic imprinting? Angelman and Prader-Willi.
25% of Turner's patient are mosaic XO/XY
10% of miscarriages are fetuses with Turner's genetics
There are over 4000 congenital conditions like Down's, Turner's and Klinefelter's
There are over 65 "disorders" of sexual development - like CAIS, PAIS, CAH, CHH, Kallman's, Swyer, De la Chappelle, etc
50% of XY individuals with ambiguous genitalia do not have a discernible genetic cause
3% of worldwide individuals born, according to the World Health Organization, have a congenital condition, sometimes multiple
It is estimated that variations of sexual development affect 1-2% of the world population