Components include:
gonads: in the male these are two testes.
[note: the testes then produce testosterone from the Leydig cells of the interstitial tissue; and MIS or mullerian inhibiting substance from the Sertoli cells of the seminiferous tubules of the testes. The testes form because the SRY (sex regulatory region of the Y chromosome) gene in the Y chromosome converts neutral gonads into testes].
internal genital development
Components include:
gonads: in the female these are two ovaries
[note: the ovaries do NOT produce testosterone and they do NOT produce MIS. Nor do they produce a special female differentiating hormone. It is the absence of these two male hormones that lead to female development of the embryo]
internal genital development
[note: the rest of the vagina comes from the urethra; and the rest of the passageway in males from the ejaculatory duct to the tip of the penis comes from the urethra].
Your gonads are your testes or your ovaries. Let me state that another way. On exam after exam students who do not read the notes, do not go to class, or just don't pay attention, make a stupid mistake. They don't know the difference between genitals and gonads. Do they think they are the same thing? Come on, does a penis look like a testis? Does an ovary look like a woman's vulva?
When I use the term internal genital development or structures, I am talking about the fate of wolffian and mullerian ducts.
When I use the term external genital development or structures, I am talking about the fate of the genital tubercle, folds, and swellings.
One more point to nag you about. When I ask for the fate of a structure in a syndrome, I am looking for specific things that happen. The gonad either becomes an ovary or testis (or in rare anomalies, an ovotestis). You don't just write "female" or "male" or "normal" as your response without further qualification.
The following syndromes are described in each case and the fate of all the pertinent structures is provided.
The probable origin is loss or mutation of the SRY gene in the Yp (the short or p arm of the Y chromosome). The SRY gene converts neutral gonads into testes. Hence if there are ovaries there will be NO testosterone and NO MIS.
gonads: ovaries but they become streak ovaries after birth and in the adult female
internal genital development
External genital development
Are there other features of note that you could be tested on here? Yes, they will not enter puberty (and will require medical supply of them to induce pubertal changes). They do not show Turner symptoms of height, swelling or webbed neck because they have both the X and Y pseudoautosomal regions.
They may arise from a piece of the Yp bearing the SRY gene being stuck in one of the X chromosomes at the time a sperm is being made during meiosis. Thus one X is normal and the other X has a bit of Y bearing SRY. The overall effect is like Klinefelter syndrome but without the triplication of the pseudoautosomal region.
gonads: testes
[note: if there are testes there will be testosterone from the Leydig cells and MIS from the Sertoli cells]
internal genital development
External genital development
Are there other features of note that you could be tested on here? Yes, they will be sterile. The testes make no spermatozoa because the DAZ region of Y q (the long arm of the Y chromosome) is absent. They will otherwise be as robust as any male taking this course.
In this condition one of the sex chromosomes is absent and only a single X is present. There is no SRY gene and thus development will go in the female direction. But a normal female has two X chromosomes and when there is only one X the ovaries fail to maintain their tissues and degenerate into streak ovaries. Since this is an ovary we get no testosterone and no MIS and thus female development.
gonads: streak ovaries
internal genitalia: no testosterone and no MIS, thus ....
wolffian ducts undergo apoptosis
mullerian ducts form the oviducts, uterus, and upper vagina
external genitalia: there is no testosterone, thus....
Genital tubercle forms clitoris; genital folds form labia minora; and genital swellings form labia major
Additional findings: If given hormonal treatment about the time of puberty these females can menstruate (but do not have eggs). They can become mothers through a donated egg or embryo using in vitro fertilization technology. They are usually of normal intelloigence.
For this karyotype the pseudoautosomal region is in triplicate and this leads to taller than average height. The Y has its SRY gene and thus gonadal differentiation will form testes. They are usually normal at birth. For reasons unknown a triplicate pseudoautosomal region leads to mild mental retardation (also seen in 47,XXX females and 47,XYY males)
gonads: testes but as adults they do not develop in puberty and are called pea-sized testes
internal genitalia: in the embryonic form the testes release enough MIS and testosterone to function normally, thus
wolffian ducts form the sperm transport system
mullerian ducts undergo apoptosis
external genitalia: testosterone is present in embryo in normal amounts and thus
genital tubercle forms glans; genital folds forms penile shaft, and genital swellings form scrotum.
Other features: at puberty breast development may occur in males and require breast reduction through surgery. The small testes are sterile and azoospermic.
Note that this term tells you several things. A true hermaphrodite by definition has both ovarian and testicular tissue. It also tells you that a chimera is composed of two different zygotic lines, one having been a potential male twin and the other a potential female twin. Instead the two zygotes somehow got together to form one embryo that is a mixture of these two genotypically different zygotes.
gonads: both ovarian and testicular tissue are present.
[Note: This can be any combination of ovary plus testis or either gonad plus an ovotestis or two ovotestes. This will lead to problems of differentiation depending on what gonadal tissue is near the wolffian or mullerian duct].
Internal genital development
wolffian: on the side that has a testis or mostly testicular tissue, you might get parts of the sperm transport system (such as epididymis or vas deferens, etc.). On the side that has an ovary or mostly ovarian tissue you might get apoptosis of the wolffian duct.
mullerian: on the side that has a testis or mostly testicular tissue, you might get apoptosis and thus NO mullerian derivatives. On the side that has an ovary or mostly ovarian tissue you might not get MIS and thus the duct becomes am oviduct, deformed uterus, and upper vagina.
External genital development:
depending on the amount of testosterone that reaches the external genital rudiments, you will either get a normal female vulva (virtually no testosterone reaching this region) or more likely an ambiguous external genitalia consisting of penis and split or bifid scrotum with a vaginal opening between the two parts of the open scrotum.
In this condition a gene on the X is involved in forming receptors to testosterone. These are absent in most or all of the target tissue when that gene is mutated. They are of karyotype 46,XY and should not be confused with 46,XY sex reversal which has a different mechanism and outcome. In CIAS the SRY gene function is normal and testes form and produce both testosterone and MIS.
gonads: testes
internal genitalia: no receptors to testosterone and thus it acts as if no testosterone is present; MIS function is perfectly OK.
Wolffian ducts may not respond to testosterone if receptors are absent and thus no sperm transport system
mullerian ducts: will undergo apoptosis in presence of MIS
external genitalia: no receptors to testosterone so it's as if there were no testosterone present, hence....
Genital tubercle forms clitoris; genital folds form labia minora; and genital swellings form labia majora.
Additional features: These are female at birth and look like baby infant girls; they are raised as females and respond to life as females. They lack a uterus, oviducts, and upper vagina hence their lower vagina (urethal in origin) is short and surgical correction may be needed for normal sexual intercourse. They develop normal sized breasts at puberty but do not develop public or axillary hair. They lack a menarche, of course, because they have testes, not ovaries. The internal testes are removed once the condition is diagnosed because internal testes lead to gonadoblastoma a potentially lethal cancer. These females have normal male levels of testosterone. They cannot become mothers by IVF because they lack a uterus.
In this condition a mutation leads to failure of receptors for the MIS hormone. It is an X-linked trait and thus appears in 46,XY males. The SRY leads to testes formation and both testosterone and MIS are produced. The defect is one of response to the MIS. Testosterone function is perfectly OK.
gonads: testes
internal genital development: testosterone function is normal; MIS is produced but cannot enter the mullerian ducts....
Wolffian ducts form a sperm transport system due to the testosterone
mullerian ducts fail to bring in MIS and thus develop as if it were not there resulting in fallopian tubes, uterus, and an upper vagina.
External genitalia responds normally to testosterone and thus...
genital tubercle is penile glans; genital folds form penile shaft; and genital swellings form scrotum.
Additional features: may lead to hernias with uterus entering inguinal canal or scrotum; may lead to abdominal illnesses such as endometriosis later in life. They can be healthy virile males who are fathers. They may die before autopsy reveals they had a uterus and oviducts.
There are many forms of this autosomal recessive condition. About 10 or more genes have been identified for the pathway in the adrenal cortex that converts cholesterol into steroid hormones. The two major hormones are cortisol and aldosterone. Aldosterone is a salt regulator. If in excess, salt is retained and leads to hypertension. If in deficit (i.e., absent) it leads to salt wasting and shock or death as in "heat stroke." Some of the conditions involve both a salt imbalance and a cortisol imbalance. Some are just cortisol abnormalities.
For the XX zygote with CAHS: This is a classical case of a female pseudohermaphrodite
gonads: are ovaries. [Thus in the early sexual differentiation things will go in a female direction. There will be no MIS nor will there be testosterone at this early stage].
Hence for the internal genitalia (formed shortly after the gonads differentiate):
wolffian ducts undergo apoptosis
mullerian ducts develop into the uterus oviducts and upper vagina.
External genitalia [these form after the internal genitalia form and about the time that the adrenal glands have enlarged in the CAHS embryo]. These will feel the influence of rising testosterone levels coming from the adrenal cortex because testosterone is a precursor to cortisol formation (testosterone is normally converted into cortisol in the adrenal cortex).
genital tubercle enlarges to form a penile glans
genital folds begin to turn into a tube and resemble a penile
shaft
genital swellings may form an incomplete scrotum that is split (bifid) with a vaginal entry between the two halves of the split scrotum.
Additional considerations: At puberty menarche will occur. If the individual had a penis and full scrotum menstruation will be cyclic and through the penis. If the child had surgery as an infant and raised female she will likely become a mother. There is a higher risk of lesbian orientation in CAHS females. Infants with salt wasting or salt retention may die if not treated for the aldosterone deficit or excess. Children with this condition are usually patients of endocrine specialists for life. Girls raised after surgery as infants usually are identified as "tomboys" by their normal sisters or other girls.
For the XY embryo with CAHS [known as Infant Hercules or Macrogenitosomia praecox] [note that he is not a pseudohermaphrodite]
Since these are males who will experience extra amounts of testosterone in late organogenesis and later in childhood, they will have exaggerated effects of testosterone and normal consequences of their MIS.
Gonads are testes
internal genitalia:
the wolffian ducts form a sperm transport system
the mullerian ducts undergo apoptosis
external genitalia - the extra testosterone exaggerates their development
genital tubercle forms penile head
genital folds form penile shaft
genital swellings form scrotum
But these look much more like an adult and are larger at birth than other baby boys. They also are likely to be melanized (darker) and to be accompanied by pubic hair.
Additional findings: The boys will be more muscular and aggressive and may end u[p bullying other kids in elementary school and will be taller than other boys. But their bones will mineralize faster and stop growing so that at puberty they will be left behind in growth and end up as the smallest boy in class.
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