When we hear that a friend’s family has a baby, naturally, our first question may be, “Is it a boy or a girl?” Sometimes in the street, there is a stranger and you pass by, you may be in the heart of the question: “male or female ah?” Sex, consciously or unconsciously, is a mysterious topic that concerns people. But I say, the actual situation is far more complicated than we think. You may say, “What’s so hard about it? Listen to the voice, look at the movement. Look at the throat knot, look at the chest ah. The most accurate or just look at the bottom (a little embarrassed). Show you the following (see below): above: my phone captured in four children, both male and female, please identify you how? Dumbfounded it. Did you know? External genitalia can look like this series (see below). There are times when the identification of men and women by external genitalia is not reliable. Above: Prader staging The world of sex is really not simple. I’m just going to take a quick look at it today. Chinese is very simple, only one word “gender”, but in English there are two words “sex” and “gender”. Do you know the difference between them? It refers to what is identified in the mind above and not what is expressed below. Sex refers to the biological concept of gender. The key is the existence or non-existence of the Y chromosome. 2, gonadal sex, is the testes or ovaries of the problem. In the early embryonic stage, there is only primitive gonadal tissue, whether it is developed into ovaries or testes, it is crucial to see whether there is a sex determination gene, which is usually on the Y chromosome. 3. Phenotypic sex, including external genitalia and internal ducts. It is the same when the embryo starts, and whether the internal and external reproductive structures develop into male or female is again determined by the hormones secreted by the gonads. Believe it or not, a sex can make people dizzy. First of all, the chromosome, a “normal” person, I added quotation marks, because no one in the world is normal, more or less have a variety of genetic defects. Well, let’s talk about a “normal” chromosome, as we all know, there should be 46 (23 pairs) of chromosomes, half from the father and the other half from the mother. The pair that determines gender is called the sex chromosomes, which are (XX) for women and (XY) for men. Above: A chromosome diagram of a man. The first 22 pairs are called autosomes. The sex chromosomes are one X and one Y. If the sex chromosomes are two X’s, it is a woman. The problem is that in rare cases, the sperm of the father or the egg of the mother can have some division errors, resulting in an increase or decrease of some chromosomes in the sperm or egg, such as the famous 21-trisomy syndrome is that people with this syndrome have an extra chromosome 21. Similarly, such errors can occur with sex chromosomes, where a sperm or egg can get two sex chromosomes, or zero sex chromosomes, resulting in a fertilized egg with 47 or 45 chromosomes. By this logic, there is even a chance of 48 or 44 chromosomes, or even more or less. It’s a bit hard to understand at first, isn’t it? That is, there may be more than one chromosome type in the population: 45, X; 47, XXY; 47, XYY; 47, XXX; or even more than one in the same individual, chimeric like 46, XX / 47, XXY, or even heterozygous chimeric like XX / XY. Some of these people may have abnormalities that are immediately apparent, but others can lurk among us “normal” people and remain undetected for the rest of our lives. Maybe you, who think you are normal, are one of them (too scary, right?). Are you now starting to feel unsure of what is normal and what is not? Let’s get to know the X and Y chromosomes. The X chromosome is big and carries about 2,000 genes, while the Y chromosome is small and has only about 86 genes. there are no life-threatening genes on the Y chromosome, and I say that for a reason. Did you know? About half of the world’s population is without a Y chromosome and actually lives to tell the tale. (Oops, whoops, answer: women, don’t forget the XX). And without the X chromosome, a fertilized egg cannot survive, and then you can understand: 45, Y and 46, YY and even 47, YYY are not then. Why is the Y so short? Some studies have shown that the Y chromosome is losing genes at a rate of 4.6 genes per million years, and at this rate, it is inconceivable that there will not be a man for 20 million years, which is a bit worrying. Generally speaking, people who have Y will behave as men. So how does the Y chromosome determine gender? The most important thing is that there is a sex-determining gene called SRY on it, and the SRY has to be functional to do so. Without SRY or if SRY is not functional, even if there is a Y, it must appear as a female. So it is easy to understand that there are 46, XY females in this world because there is no SRY on Y or SRY is not activated. Although the SRY gene is usually on Y, it is occasionally transferred to X, and this SRY is still functional, so it is not hard to understand that there would still be 46, XX males in this world. The problem seems to be starting to get complicated. 46, XX is usually a woman, but can also be a man. 46, XY is usually a man, but can also be a woman. Are you starting to get confused about what a man and a woman are? Let’s talk about the gonads and ductal system. The gonads are not differentiated until 6-7 weeks of embryonic life: they are neither male nor female, and there are two sets of ducts waiting to evolve. Below: green is the primitive gonad; blue is the mesonephric duct, which mainly forms the male reproductive duct; red is the paramedian duct, which mainly forms the female reproductive duct. After gonadal differentiation, one of the two sets of ducts will continue to develop while the other will degenerate. At 6 weeks of gonadal differentiation, if SRY is present, it is activated, and then the other genes are activated in turn, and the undifferentiated gonads are transformed into testes. If SRY is not present, different genes are activated and the undifferentiated gonads are transformed into ovaries. But it takes two X chromosomes to have normal ovarian development. Due to the strong maternal estrogen levels during pregnancy, the female fetus has a rather weak role for the little estrogen secreted by the ovaries and will continue to develop into a female, following the female route set by the system by default. The newly formed testes of the male fetus, on the other hand, can produce testosterone at about 16 weeks at levels even comparable to adult males. Testosterone promotes the development of the mesonephric duct, while another hormone secreted by the testes degrades the paramedian duct, and only after such a struggle does it develop into a male. Above: Eventually the origin of the ducts of the genitourinary system in men and women (blue mesonephric duct, red paramedian duct, green urogenital sinus). This process, if disturbed, can lead to developmental stagnation or confusion, masculinization of the female or feminization of the male, such as a male with residual paramedian tubules and a pseudovagina or small uterus, while a female with residual mesonephric tubules can form cysts in the body. The external genital development is the same for both sexes, with the default state for females: if there is no dihydrotestosterone (converted from testosterone), the external genital structures will develop along female lines; if there is dihydrotestosterone, they will develop along male lines. Females with abnormal androgens will exhibit clitoral hypertrophy, whereas males with insufficient androgens, or with insensitive receptors for androgens, will exhibit hypospadias, vulvar obscuration, or female vulva. During childhood, sex hormone levels are very low in both boys and girls. In both boys and girls, there is a period of elevated sex hormones during the first few weeks of life. This period is called “mini-puberty”. In the teenage years, the brain and hypothalamus begin to produce neurohormones, and the ovaries and testes begin to produce large amounts of sex hormones, causing the child to enter “puberty,” when the body changes dramatically to complete the stereotype of male and female. Some children’s gender issues only become apparent at this time. Therefore, sometimes it is not that easy to identify sex, but we need to look at gonads, external genitalia, internal genital ducts, hormone levels, chromosomes and genetic tests together. Gender, is not black or white, nor is it a gray scale, it is color. But again, we always have to try to segregate into male and female. Perhaps it is more important for us to accept, recognize, tolerate, and respect. As a simple-minded surgeon, these questions about abnormalities in sexual development are often beyond one’s intelligence, so it is often necessary to call in a few professors from the pediatric endocrinology department to do the thinking. If lifelong hormone replacement therapy is needed, the professors of pediatric endocrinology must also be consulted. As a simple-minded surgeon, I do the physical work, such as surgical exploration of the gonads and internal ducts, gonadal biopsy if necessary, gonadectomy or testicular drop if necessary, and other minor things. Once you’ve decided to be male or female, you can also do some tinkering to make the internal and external genitalia a little more gender-appropriate. If it can be checked out and treated with targeted medication or surgery, it is still possible for many children to lead a relatively normal life. It is better to deal with abnormalities in sexual development sooner rather than later! Unfortunately, chromosomal and genetic problems are currently impossible to solve. This also determines the limitations of certain current treatments. To make such a science, it is especially important to remind that it is important to think that a child may have abnormal sexual development if: Neonatal period: 1. external genitalia are vague and plausible; 2. female in appearance, but with an enlarged clitoris and swelling in the groin or below the labia; 3. male in appearance, with untouched testes bilaterally, hypospadias with cryptorchidism, and a very small penis; 4. external genitalia and karyotype of chromosomes inconsistent. Older children: 1. blurred external genitalia; 2. bilateral inguinal hernia in girls; 3. delayed or incomplete puberty, e.g., masculinization in girls, girls who should have but did not have menstruation, breast development in boys, intermittent meatus hematuria in males. If you have a child like this around you, I hope you will remember that I have spoken to you about abnormal sexual development. The patient’s needs are always the starting point for the doctor’s exploration, and the patient is always the doctor’s truest teacher.