Male and female development
As a sexed species, humans develop as either male or female.
The reason sex exists is to serve as a mechanism for producing young. Humans are anisogamous, i.e. our method of sexual reproduction involves the fusion of a small gamete with a large gamete. Thus the sexes are defined by the gamete type that their reproductive anatomies are organised around. Male bodies are organised around the production of small gametes (sperm); female bodies around the production of large gametes (eggs). As there only two gametes, there are two sexes, and our species is sexually dimorphic (from ancient Greek meaning ‘two forms’).
There is of course enormous variation within these two types, creating a spectrum of body types. This is sometimes claimed as evidence that sex is not binary or even that sex itself is on a spectrum. But it is incorrect to define the sexes in terms of these variable bundles of characteristics. Sex is not defined by chromosomes, hormones, or secondary sexual characteristics but by gamete type.
The sex of a human being is decided at conception, i.e. when the sperm fuses with the egg to form a zygote with a complete genome. The egg always supplies an X chromosome. The sperm provides either an X or a Y: a 50% chance of each. In 99.8% of cases the resulting zygote has the typical sex chromosomes (so-called) of either XY (male) or XX (female) and goes down a typical pathway of phenotypic development. People with rare DSDs (the other 0.2%) may have atypical karyotypes or phenotypes but are still male or female; to claim they are neither, or some mixture of the two, is false and dehumanising.
Sex differentiation
No sexual differences can be observed in the fetus until the sixth or seventh week of gestation. The key to sex determination is the activation or non-activation of the SRY-gene on the Y chromosome (though other genes also come into play). If/when this gene is activated, the fetus becomes male and develops testes; in the absence of SRY activation the fetus becomes female and develops ovaries. For this reason biologists sometimes call the SRY gene a ‘master switch’ since the fetus will develop into a female unless the gene is activated.
Thus chromosomes determine sex – they supply the instructions for how it should develop – but are not the same as sex. We can clarify this with a couple of examples of DSDs:
- If the fetus has XXY, the presence of the Y chromosome still leads to SRY activation and the fetus becomes male. The variation in karyotype is not a new sex; it merely produces an atypical male.
- A fetus with XY in whom the SRY gene does not activate will develop as a female. Despite her XY chromosomes she is not a male but an atypical female.
Note this process also depends upon the fetus’s cells being able to respond to androgens (the male sex hormones required for male sexual development). If the cells are insensitive to those androgens (as in the DSD known as Complete Androgen Insensitivity Syndrome or CAIS, in which cells’ androgen receptors are rendered inactive by a mutation) then the fetus won’t respond to the masculinisation process and will become female despite having XY chromosomes.
In summary: to become male, a fetus needs 1) a Y chromosome with an activating SRY-gene in combination with 2) functioning androgen receptors. Failing this, the fetus will be female.
Pathways of development
The sex of an individual is defined by his or her pathway of development. Before sexual differentiation, an embryo possesses both Müllerian and Wolffian ducts: precursor structures that will develop into the reproductive organs. [1] Once sex differentiation kicks in, it retains one and loses the other.
- Müllerian ducts develop into the female reproductive system, organised around large gametes (eggs)
- Wolffian ducts develop into the male reproductive system, organised around small gametes (sperm)
These two pathways of sexual development are mutually antagonistic and cannot functionally co-exist, as humans are not hermaphrodites. If the embryo is sent down the male pathway, it produces anti-Müllerian hormones that actively suppress the female structures.
Even if a given person’s reproductive anatomy is not fully developed or fully functional, e.g. s/he is infertile and does not actually produce any gametes, they are still male or female as their body developed down one pathway or the other. It would be most offensive for example to tell a woman who was born without a cervix, or has had her ovaries removed due to cancer, or has gone through menopause and thus no longer produces eggs, that she is therefore not female.
Gonads
They also secrete hormones responsible for the development of primary and secondary sex characteristics, and are thus considered to be part of the endocrine system. I’ll discuss that separately.
Testes
The testes are a pair of oval organs that have two functions: to produce sperm, and to produce hormones, especially testosterone.
In humans they are descended, i.e. they hang between the legs in a sack of skin called the scrotum. This is to distance them from the rest of the body, because sperm production requires a slightly cooler temperature, about two or three degrees Celsius lower (it’s not known for certain why, or how the curious phenomenon of descended testicles evolved).[2]
Sperm are created (the scientific term is spermatogenesis) in a system of tightly coiled tubes called seminiferous tubules, where cells known as germ cells divide and develop to form organisms resembling tadpoles, with a head and tail – namely sperm. The process takes about three months. Afterwards the sperm are stored for a few days in a long, coiled tube behind the testicle called the epididymis where they mature and learn to swim. Once mobile, they are ready to attempt fertilisation.
Boys start producing sperm when they hit puberty (on average around age 13), a milestone called ‘spermarche’ for what it’s worth. A man produces millions of sperm cells a day, and about 525 billion over his lifetime.
Ovaries
The ovaries, too, are a pair of oval organs with two functions: again, to produce gametes and to produce hormones. This time, the gametes are eggs (or ova, singular ovum) and the hormones are oestrogen and progesterone.
The term ‘egg’ is a little vague and gets used for different stages of the process. To be precise, the ovaries produce oocytes, or immature egg cells. These oocytes are created from germ cells by a process called oogenesis which takes place when the baby girl is still in the womb. Most of these 7 million oocytes die before she is even born. Whereas the testes produce new sperm continuously, females are born with about two million oocytes, which in principle is the maximum number of eggs she can produce in a lifetime. By puberty she is already down to about 300-400,000, of which maybe 300-500 will actually get ovulated during a woman’s reproductive lifetime. The number and quality/viability decline with age.
The oocytes are found in structures inside the ovaries called ovarian follicles. There are hundreds of thousands of these, the great majority of them with an oocyte in the centre. Once a month an oocyte breaks out of its follicle as part of ovulation, which we’ll get to in a second.
Meiosis
The gonads create gametes through a process of cell division called meiosis.
A cell has a life cycle: it comes into existence when it divides from a so-called ‘mother’ cell, it reproduces by dividing into two, and at some point it will die or be replaced.[3] In a process called mitosis, a cell divides itself into two identical cells, with an exact copy of its DNA in each. All the cells involved are ‘diploid’.
- Diploid: a cell with two sets/copies of chromosomes in the nucleus (46 in humans).
Meiosis is a bit different and more complex, as a gamete by definition has only half the genetic information. So meiosis needs to halve the 46 chromosomes to 23. This division requires a two-step process (we needn’t go into detail about the reasons why, but they are explained in this video if you are interested). Whereas in mitosis the original diploid cell divides into two new diploid cells, in meiosis it divides into two new ‘haploid’ cells.
- Haploid: a cell with just one set/copy of chromosomes (23 in humans). Gametes (egg or sperm cells) are the only haploid cells in the human body.
Then the two new haploid (23-chromosome) cells themselves duplicate, mitosis-fashion, into two further haploid cells, and these are the gametes. Thus one starting cell can produce four gametes.
Meiosis therefore serves just one purpose: to produce gametes, with only half the chromosomes of the original cell, i.e. a reduction from diploid to haploid. To return to the diploid state, a male and a female gamete must fuse via fertilisation.
An important process that takes place during meiosis is recombination. This is the reshuffling process by which, when creating the gamete’s genetic material, each chromosome pair swaps pieces from one chromosome with pieces from the other chromosome. Thus a father and a mother each has material from both their parents in their gametes. In this way recombination ensures genetic diversity: a child created by the father and mother inherits their genetic material, which thanks to recombination will include genetic material from all four grandparents. The child does not however receive carbon copies: there is still some variation, which means two siblings do not inherit the exact same DNA unless they are identical twins.
Gametes therefore are the haploid reproductive cells or sex cells, which come from germ cells. In humans, once again,
Both are incredibly tiny single cells that each contain only half the genetic information required to create a new human being.
Gametes
Gametes therefore are the haploid reproductive cells or sex cells, which come from germ cells. In humans, once again,
- the male gametes are sperm produced by the testes
- the female gametes are eggs produced by the ovaries
Both are incredibly tiny single cells that each contain only half the genetic information required to create a new human being.
The fact that each gamete contains half means that there need only be two. This is why there are two sexes. No third gamete exists, or could have any role to play, and thus there is no third sex (let alone a fourth, fifth or more). Although many concepts in biology have fuzzy boundaries (notoriously the concept of species), there is no room for fuzziness with gametes. One simply produces one or the other (or in some cases, none at all). There are no intermediate forms.
Sperm is short for ‘spermatozoa’, singular ‘spermatozoon’. It is an independent, single-celled living organism, about 0.05mm long, making it much too small to see with the naked eye. The plant equivalent is pollen.
The sole purpose of the tiny, torpedo-like sperm cell is to deliver a genetic package to fertilise an egg. The DNA is carried in the nucleus in the sperm’s head. It has some mitochondria in the middle to provide the energy it needs to swim through the female’s body, and it is propelled by a tail.
During sexual activity, the sperm are mixed with a white-ish fluid to form semen, which allows the sperm cells to be propelled up the urethra (the tube inside the penis, the same tube pee comes out of), and travel into the female’s body. The penis is a delivery mechanism to get the male’s gametes within travelling distance of the female’s.
Whereas the male strategy is to hurl out a vast number of cheaply produced contenders in the hope that one of them wins the prize, the female strategy is to make far fewer, much more expensive investments. The round egg cell is 10,000 times the size of a sperm cell. At about a tenth of a millimetre it is just about visible to the naked eye – about the size of a full stop. This makes it a giant among cells, and the largest in the human body. This is to maximise the likelihood of the offspring surviving: while the sperm only passes on its nucleus, the egg cell has to provide enough energy for the new human being it will develop into.
The core of the cell is the nucleus, which contains the 23 chromosomes. The cell’s structures are held together by a kind of gel called cytoplasm. Then there are some outer layers: a cell wall or membrane called the zona pellucida, then a surrounding layer called the corona radiata that provides proteins to the cell.
We have seen that gametes are created by meiosis and that meiosis has two stages. The oocytes enter the first stage of meiosis before the girl is born, then stop before completing it. They are still stuck at this point when the girl is born, and stay that way until puberty.
Once the girl hits puberty her reproductive cycle begins, or what is actually two concurrent cycles: firstly the ovarian cycle which matures and releases eggs, and secondly the menstrual or uterine cycle, which prepares the uterus to handle any eggs. One egg is activated each month in a process called ovulation: some of the ovarian follicles along with their oocytes will begin to grow, until one of them wins the race by growing faster than the others. That oocyte finally completes the first stage of meiosis and breaks out of the follicle, leaving the ovary to travel down the fallopian tube, which serves as a passageway to the uterus.
If the egg gets fertilised, it undergoes the second phase of meiosis to become, briefly, an ovum (i.e. a mature female gamete or sex cell) – but only until the sperm nucleus fuses with the egg nucleus, whereupon it becomes a ‘zygote’. The terms can be a bit confusing, because technically the cell is an ovum for barely any time at all, but you will often hear the term ‘ovum’ used more loosely, and ‘egg’ more loosely still.
After ovulation the egg lives for 12-24 hours. It may or may not get fertilised by a sperm during that time, but either way, it travels on into the uterus.
Since gametes are haploid cells with only half the genetic information required to make a new human being, two (one male, one female) have to fuse together to complete the set. This is the role of sexual intercourse: to bring gametes from two individuals together. The successful joining of the sperm and the egg is called conception.
Once ejaculated during intercourse, sperm swim up the vagina, through the cervix (the opening of the uterus), and through the uterus to the fallopian tube where the egg awaits. This is a relatively long and hazardous 14-hour journey, where the sperm’s swimming is heavily assisted by contractions of the uterine muscles. The sperm need to push through the corona radiata and zona pellucida to attach to the egg. The first sperm to make contact will fertilise the egg. Out of the millions of sperm released into the woman’s body during sex, only one can succeed.
Once a sperm succeeds, the egg releases proteins and enzymes that ensure that no other sperm is allowed in, and the two gametes fuse within minutes.
Fertilisation is the key moment in sex: the moment when the genetic material of the male and female parents is combined or fused. This is the whole point of sexual as opposed to asexual reproduction. In asexual reproduction, as we’ve discussed, there is only a single parent and thus no fusing of gametes i.e. of genetic material.
The genetic material of the sperm uncoils to form a male pronucleus inside the egg, i.e. at this point there are two (pro)nuclei, one from either cell. The egg at this point completes meiosis. The genetic material of the two nuclei joins together, completing the fertilisation process: a unique genetic code is created, deciding the characteristics of the new human being.
This includes its sex. As I mentioned above, sex is determined at fertilisation, because that is when the 23rd pair, the ‘sex’ chromosomes, are determined as (normally) either XX (female) or XY (male). However, the fetus does not develop its sexual characteristics until it is about seven weeks old. By the time a baby is born, its phenotype is (again, normally) fully male or female.
Sperm
Sperm is short for ‘spermatozoa’, singular ‘spermatozoon’. It is an independent, single-celled living organism, about 0.05mm long, making it much too small to see with the naked eye. The plant equivalent is pollen.
The sole purpose of the tiny, torpedo-like sperm cell is to deliver a genetic package to fertilise an egg. The DNA is carried in the nucleus in the sperm’s head. It has some mitochondria in the middle to provide the energy it needs to swim through the female’s body, and it is propelled by a tail.
During sexual activity, the sperm are mixed with a white-ish fluid to form semen, which allows the sperm cells to be propelled up the urethra (the tube inside the penis, the same tube pee comes out of), and travel into the female’s body. The penis is a delivery mechanism to get the male’s gametes within travelling distance of the female’s.
Egg
Whereas the male strategy is to hurl out a vast number of cheaply produced contenders in the hope that one of them wins the prize, the female strategy is to make far fewer, much more expensive investments. The round egg cell is 10,000 times the size of a sperm cell. At about a tenth of a millimetre it is just about visible to the naked eye – about the size of a full stop. This makes it a giant among cells, and the largest in the human body. This is to maximise the likelihood of the offspring surviving: while the sperm only passes on its nucleus, the egg cell has to provide enough energy for the new human being it will develop into.
The core of the cell is the nucleus, which contains the 23 chromosomes. The cell’s structures are held together by a kind of gel called cytoplasm. Then there are some outer layers: a cell wall or membrane called the zona pellucida, then a surrounding layer called the corona radiata that provides proteins to the cell.
We have seen that gametes are created by meiosis and that meiosis has two stages. The oocytes enter the first stage of meiosis before the girl is born, then stop before completing it. They are still stuck at this point when the girl is born, and stay that way until puberty.
Once the girl hits puberty her reproductive cycle begins, or what is actually two concurrent cycles: firstly the ovarian cycle which matures and releases eggs, and secondly the menstrual or uterine cycle, which prepares the uterus to handle any eggs. One egg is activated each month in a process called ovulation: some of the ovarian follicles along with their oocytes will begin to grow, until one of them wins the race by growing faster than the others. That oocyte finally completes the first stage of meiosis and breaks out of the follicle, leaving the ovary to travel down the fallopian tube, which serves as a passageway to the uterus.
 |
| NB: the oocyte is not to scale. |
If the egg gets fertilised, it undergoes the second phase of meiosis to become, briefly, an ovum (i.e. a mature female gamete or sex cell) – but only until the sperm nucleus fuses with the egg nucleus, whereupon it becomes a ‘zygote’. The terms can be a bit confusing, because technically the cell is an ovum for barely any time at all, but you will often hear the term ‘ovum’ used more loosely, and ‘egg’ more loosely still.
After ovulation the egg lives for 12-24 hours. It may or may not get fertilised by a sperm during that time, but either way, it travels on into the uterus.
- If fertilisation did not happen, the egg disintegrates and is ejected in menstruation.
- If fertilisation does happen, the egg implants itself in the lining or wall of the uterus where it will develop, eventually, into a baby.
Fertilisation
Since gametes are haploid cells with only half the genetic information required to make a new human being, two (one male, one female) have to fuse together to complete the set. This is the role of sexual intercourse: to bring gametes from two individuals together. The successful joining of the sperm and the egg is called conception.
Once ejaculated during intercourse, sperm swim up the vagina, through the cervix (the opening of the uterus), and through the uterus to the fallopian tube where the egg awaits. This is a relatively long and hazardous 14-hour journey, where the sperm’s swimming is heavily assisted by contractions of the uterine muscles. The sperm need to push through the corona radiata and zona pellucida to attach to the egg. The first sperm to make contact will fertilise the egg. Out of the millions of sperm released into the woman’s body during sex, only one can succeed.
Once a sperm succeeds, the egg releases proteins and enzymes that ensure that no other sperm is allowed in, and the two gametes fuse within minutes.
Fertilisation is the key moment in sex: the moment when the genetic material of the male and female parents is combined or fused. This is the whole point of sexual as opposed to asexual reproduction. In asexual reproduction, as we’ve discussed, there is only a single parent and thus no fusing of gametes i.e. of genetic material.
The genetic material of the sperm uncoils to form a male pronucleus inside the egg, i.e. at this point there are two (pro)nuclei, one from either cell. The egg at this point completes meiosis. The genetic material of the two nuclei joins together, completing the fertilisation process: a unique genetic code is created, deciding the characteristics of the new human being.
This includes its sex. As I mentioned above, sex is determined at fertilisation, because that is when the 23rd pair, the ‘sex’ chromosomes, are determined as (normally) either XX (female) or XY (male). However, the fetus does not develop its sexual characteristics until it is about seven weeks old. By the time a baby is born, its phenotype is (again, normally) fully male or female.
Chromosomes
Let us now return to the subject of chromosomes.
X chromosome: the X chromosome contains information essential to both sexes – at least one copy must be present in all human beings. It contains about 800-5000 (depending on who you ask) of the human genome’s 20,000+ genes. It’s generally said to contain 5% of a person’s total DNA.
Y chromosome: the Y chromosome is male-determining. It has about 55-78 genes (depending on who you ask), and only about 27 unique ones, most of which are related to creating sperm. The key gene is called SRY. If you have this gene and it activates, you develop into a male. If you don’t, or you do but it doesn’t activate, you develop into a female.
The egg always carries an X chromosome, so sex is determined by the sperm: 50% carry an X chromosome and 50% a Y, so when the gametes fuse, the zygote will end with either an XX pair or an XY pair. Everyone therefore inherits one X from their mother, plus either a Y or an additional X from their father.
Zygote
The fertilised egg now contains 46 chromosomes, half from the sperm (father) and half from the egg (mother), and thus contains all the genetic instructions needed to make a baby. This new, diploid kind of cell is called a zygote – the beginning of a new human being.
This cell then divides multiple times and goes through various named stages (I won’t list them all). First it divides into two cells to become multicellular, i.e. an embryo, then the embryo develops into a foetus and eventually (after nine months) a baby.
Conclusion
I am not aware of any peer-reviewed paper in the entire scientific literature that disputes that there are two gametes and therefore two sexes. If someone could produce proof that humanity has been wrong for thousands of years and that there are in fact more (or less) than two sexes in human beings, it would be one of the most astonishing scientific discoveries of all time.
Footnotes
[1] Fei Zhao, Humphrey Hung-Chang Yao, ‘A tale of two tracts: history, current advances, and future directions of research on sexual differentiation of reproductive tracts’ (2019).
[2] This incidentally means that the testes – unlike the ovaries which are safely tucked away inside the body – are exposed and vulnerable, putting a male’s genetic legacy at risk, which is why they have extra pain-sensitive nerve endings to ensure their owner protects them.
[3] You will sometimes read that the human body replaces itself every seven years, but the seven years figure is meaningless. Cells die and are replaced all the time.
I don't see why it's "dehumanizing" to say that adult humans with DSD who don't make recognizable sperm or eggs (e.g. those with gonadal dysgenesis) are not necessarily "male" or "female" in a biological sense.
ReplyDeleteIn one direction, sexual dimorphism is hardly a distinctively human trait. In the other, the "dehumanizing" claim itself seems to invoke the premise that individuals whose sex cannot be confidently classified are somehow inferior to those who successfully make large or small gametes, which I'm sure you'd agree is incorrect. Why not simply say that it is frequently useful in biology and medicine to assume that everyone's reproductive biology follows one of two functionally complementary patterns called "female" and "male", but that obviously it makes no difference whatsoever to one's humanity whether one's body follows either, neither, or a combination?
All humans are either male or female, including people with DSDs and irrespective of whether they make gametes or not. Obviously their humanity should be respected regardless.
DeleteIf someone is male and you say they aren't, or if they are female and you say they aren't, you're denying a fundamental part of who they are. That's what I meant.
To your conclusion: there are not two but quadrillions of human gametes out there, and the question of whether we should assign each of them to one of two categories is a theoretical one, not an empirical one. That said, there has certainly been peer-reviewed work describing atypical gamete development in DSD at the morphological, functional, and genetic levels. A sterling recent example of the latter is Wang 2021 (https://www.nature.com/articles/s41419-021-03676-x), describing tissue that produces non-functional cells resembling eggs and immature spermatozoa:
ReplyDelete>Infertile ovotestis (mixture of ovary and testis) often occurs in intersex individuals under certain pathological and physiological conditions. [...] Here, we report the first comprehensive single-cell developmental atlas of the model ovotestis. [...] We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells.
By 'two gametes' I mean two gamete types, not that there are only two actually existing gametes in the world - I should have thought that was obvious. And their categorisation is not purely a 'theoretical' matter because the material world including sex very definitely exists. Take this sophistical nonsense elsewhere.
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