The Truth About Biological Sex

Abiya Syed
Jul 5, 2024
4 min read

Updated: Jul 29, 2024

We all have the letter on our passports, identification cards, and half a dozen documents—F for female and M for male. This is our assigned sex at birth, and while it may seem like a simple and static reality, it isn't as straightforward as we are led to believe. There are hundreds of delicate processes involved in creating biological sex, starting from birth and continuing for the rest of our lives, which may go "wrong" at any moment and veer off the prescribed path, often without our knowledge or understanding.[1]

Chromosomal Sex

Your entire sequence of genes—your genotype—is created during fertilization. This is when your father's sperm cell fused with your mother's egg cell to create the zygote, which multiplied rapidly to create all the cells in your body. The sperm cell and egg cell contain half of each parent's genotype, which includes sex chromosomes.

In placental mammals, a sex chromosome can be either shaped like an X or Y. Femaleness is indicated by two X chromosomes, and maleness by one X chromosome and one Y chromosome. This means you always receive an X chromosome from your mother, and your sex, known more specifically as your chromosomal sex, is usually dependent on whether you receive an X or Y chromosome from your father.

Two sets of sex chromosomes are depicted - female (XX) and male (XY). — The sex chromosomes on a karyotype

From Socratic Q&A Biology [2]

Aneuploidies, or an issue with the distribution of the X and Y chromosomes, can result in the chromosomal sex being irregular.[3] For example, monosomy X (or having only one X chromosome) results in Turner syndrome, which has symptoms such as short stature, delayed puberty, and infertility.[4] Various trisomies (having more than two sex chromosomes) result in Klinefelter syndrome (XXY), XYY syndrome, and XXX syndrome. Klinefelter syndrome, which is the most common of the three, occurring in roughly 1 in 500 births, results in male children with low testosterone, and reduced muscle mass, facial hair and body hair.[5]

Genetic Sex

At six weeks of development in the womb, the fetus differentiates into either a male or a female fetus. Up until this point, both ovaries and testes were being developed, but the activation of either testosterone in the case of a male or estrogen in the case of a female withers away the undesirable sex organs and promotes the growth of the desired organs.

A single gene, the SRY gene in the Y chromosome, triggers the development of male sex organs and the male hormonal cocktail. Sometimes, this portion of the Y chromosome can be present in an XX fetus, causing the fetus to develop as male. At other times, this gene can be absent in Y chromosomes, causing an XY fetus to develop as female. This phenomenon can mean an inconsistency between the chromosomal sex and genetic sex, which often goes undiscovered unless a full genotype analysis is done.

A similar malfunction can occur with the WNT4 gene, a gene that promotes the development of female sex organs and hormones. This gene, when doubly present in an XY fetus, can cause the development of atypical male genitals and gonads, as well as a rudimentary uterus and Fallopian tubes. Phenomena such as these are called disorders of sexual development, and occur in as many as 1 in 100 individuals.

Researchers have found over 25 genes that contribute to disorders of sexual development. For example, congenital adrenal hyperplasia (CAH) as a result of a 21-hydroxylase deficiency, a genetic condition, results in the excessive production of male hormones in XX individuals. It can result in effects as severe as abnormal genitalia that resemble a cross between male and female genitals, or as mild as body hair patterns resembling biological males. It can also result in irregular periods and infertility, which is often how those with this condition discover they have it.

Anatomical or Biological Sex

Studies in mice have led to the discovery that sex does not remain static after birth. The deactivation of Fox12, an ovarian gene present in mice, resulted in a shift of cells from those that supported egg development to those that supported sperm development. Similarly, the deactivation of Dmrt1, a testicular gene, resulted in the shift of the mice’s cells to ovarian ones. It is possible that epigenetic changes can result in changes in anatomical sex.

Disorders of sexual development can also be caused by malfunctions in organs, hormones, or glands. For example, complete androgen insensitivity syndrome is a result of body cells being unable to process testosterone, which results in an entirely female body despite the presence of male hormones.[6] This syndrome often goes unnoticed until puberty, where the lack of menstruation and other sexual development indicates irregularity in development. Similarly, partial androgen insensitivity syndrome can result in abnormal genitalia and other effects on anatomical and sexual development.

Cellular Sex

Biological sex is further complicated when we look at individual cells, as many people do not have the same genetic material in all their cells.

Some individuals have an unequal distribution of sex chromosomes, known as mosaicism. During division, the Y chromosome can be lost in XY cells, resulting in X cells. If the X cells make up a large portion of the embryonic cells, then the child is born a female with Turner syndrome. This causes a restriction in processes associated with puberty, such as an increase in height and the development of ovaries.

Another possibility is fraternal twins of different sexes fusing in the womb to create one baby, resulting in a genetic chimera, or microchimerism, where stem cells from a mother's body are exchanged with those from the fetus. This results in variation in cellular sex, which can, in rare cases, result in a disorder of sexual development.

In conclusion, biological sex is a combination of many aspects—chromosomes, genes, hormones, anatomy, cells—and the line between male and female is not as discrete as it seems. The real facts and figures on how many individuals have a disparity in the sexual identity of different parts of their body is unknown, and it is possible that with further study our understanding of biological sex will be completely and permanently altered. Perhaps, someday in the future, the M/F question will be eradicated entirely.