SEX IS ALWAYS COMPLICATED, OR CAN YOU REALLY KNOW IF YOU ARE A BOY OR A GIRL?

You walk into a bar on a night out in search of an individual to lay your eyes on, whichever sexual orientation you may be, a key strategy in your search will be singling out the sex of the target of your affection. Asked on the street, most would surely say identifying male from female is not a difficult task, however, recent research suggests that our long held belief that sex is dichotomised is in fact a fallacy.  Typically, we think of sex as defined by the presence or absence of two X chromosomes, simple; yet, a cohort of extreme cases with disorders of sexual development, such as with transsexual persons with abnormal genitals, have shown physicians that we may walk the line of male/female sex.

Delimiting male and female becomes more than a complex question of how to raise a transsexual child when we consider the genetic data underpinning this boundary (For the review paper, click here). For instance, a case study of a woman receiving a test for genetic abnormalities in her foetus found that although her baby was fine, she was composed of two distinct groups of cells, one male and the other female – only in her late forties had she discovered she was perhaps not entirely female! These finding are increasingly common and lead to the conclusion that we are a cellular patchwork quilt of genetically heterogeneous cells. What is more interesting is that there is some evidence to suggest that the sex of these cells may be informative for function and behaviour. These microchimaeric cell populations appear in mice models not be idle in their "foreign" environment, and infant adapt and adopt specialised functions for the host. Unfortunately, it is, as yet unknown whether these sex differences have a deleterious effect on the tissue behaviour, sexually dimorphic immune responses, for example.

However, my immediate question is “is this just another academic nicety, or does this variation actually have an impact on how we should understand physiology?”. One answer is, yes, regardless of these cellular variations, there is a very well-understood process from foetus to baby that defines whether a child will one day carry a baby to term or will just contribute the building blocks in the form of sperm.

Yet, even the common belief that  we are born female and develop from there in to males from  a series of endocrine cascades has recently been challenged. Although initial findings of the SRY gene that alone may induce testicles to develop over the seemingly default ovaries, recent genes that actively suppress testicular development and favour ovaries call this into question. This subtle genetic trade-off appears to paint a more complex picture than we may expect, more of a battle between the male and female phenotypes.

We might expect that the male and female phenotype struggle against each other in early, in utero, development, or even perhaps for some sensitive period in early life, however, it is possible that the battle of the sexes persists long into adulthood. Evidence from mice studies show that by activating or deactivating a particular set of genes, the cells that initially supported the production of female eggs transform to those cells that produce sperm and visa versa - we can see post-natal cell regulatory effects on the sex of our physiology! Yet, this may not be as shocking as you or I first perceive it; there are epigenetic (within-lifetime genetic regulatory) effects in at least 25 genes typically associated with disorders of sexual development, found in "normal" individuals, which suggests that even for the average person sex is on a continuum, and that differences need not be as dramatic as in disorders such as hermaphrodites. Nonetheless, it will often be the shocking examples, such as the elderly man who discovered at the age of 70 that he had womb!

If we step back a little form the catchy headlines for a minute these finding present a profound question "can we assume that each cell contains the same set of genes"? A core tenet of even high school biology, it appears this may not be the case! In fact, this  may be the take-away point of the question of sex defined as binary. However, we should also ruminate on the social implications of sex as a spectrum. What will it mean if this line of research gains enough momentum to make us truly question what it means to be female or male; must we then alter our attitudes on the questions of equality; should we re-examine the legal and cultural boundaries that centre on what seems an immovable basis of our understanding of ourselves? Whichever we choose, what exists in the literature at present is at the very least food for thought, but I hope it has made you question how you think of sex!

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https://ia601506.us.archive.org/7/items/SexRedifined/sx.mp3