04 - Disorders of Sexual Development (intersexes)

Question 1

1. Disorders of sexual development: any congenital condition in which what?
2. What is intersex?

Answer 1

1. the development of chromosomal, gonadal or antatomical sex is atypical
2. shows ne or more anatomical features of both sexes

Question 2

(Chimeras)

1. an animal composed of a mixture of what?
2. Thought to occur by amalgamation of what?

can also occur by (less commonly)

3. a readily detectable chimera would have what combo of cels ?
4. Can you have XX/XX or XY/XY? would they result in abnormal sex differenation?
5. Can XX/XY chimeras be fertile?
6. Males generally outnumber females by what margin?

(true hermaphrodites occur but are less common)

Answer 2

1. genetically different cells which originate from different zygotes
2. usually 2 different early embryos which then continue development as single individual

fertilization of an oocyte contating 2 nuclei

(rare in nature but do occur.. mostly in labs - sometimes across species)

3. XX/XY
4. yes… but these are more difficult to detect ; no
5. yes… depends on balance of XX and XY somatic cells in early gonad
6. 3 to 1

Question 3

(Mosaic)

1. These are also composed of 2 (or more) cells lines… but what?
2. So what happens?
3. They arise from what?
4. Most likely to be seen in sex chromosomes… why is this?
5. What are three possible examples? could these also be chimeras?

Answer 3

1. arise from single zygote
2. early in embryonic development chromosome lost from one cell and all cells in lineage will be missing same chromosome (the chromosome may be added to another line of cells)
3. disorders of mitosis during cell division (mitotic non-disjuction) where chromosomes don’t separate normally
4. all autosomal monosomies and most trisomies are lethal during embryonic development (resulting in death of cell lines/embryos)
5. XY/XO, XX/XO, XY/XXY; yes (further genetic studies (banding) needed to be done to know)

Question 4

Will all chimeras and mosaics present as intersexes?

depends on what?

Answer 4

no

chromosomal constitution and proportion of gonadal cells involved

Question 5

(Hermaphrodite)

1. combo of male/female in greek myth

(true hermaphrodite)

1. What do true hermaphrodites have?
2. What are possible combos?
3. how common in males?

Answer 5

1. both ovarian and testicular tissue
2. one ovary and one testicle, ovotestis, or any combo
3. rare

Question 6

(true hermaphrodite cont)

1-2 under what two conditions can they occur?

3. will resultant sexual phenotype be male, female, or hermaphrodite?

depending on what?

Answer 6

1. when timing of expression of SRY is shifted later so that it overlaps with ovarian development
2. when male/female supporting cells are simultaneously present in developing gonad

example XX/XY chimeras and XY/XO mosaics

3. could be any

ratio of Y contating cells to other types in gonad

Question 7

(Define these)

1. abnormality of phenotypic sex… chromosomal and gonadal sex are the same but the phenotype of the internal and/or external genitalia show some features of the opposite sex

classified on what basis?

2. Has XY chromosomes and testes but female characteristics of internal or external genitalia
3. Has XX chromosomes and ovaries but masculinized genitalia

how common?

(Though they are the traditional way of classification, not all intersexes will fit neatly into the above categories. This is especially true in sex-reversal, where genetic sex does not agree with gonadal)

and phenotypic sex.

Answer 7

1. pseudohermaphrodite

their GONADAL sex

2. male pseudohermaphrodite
3. female pseudohermaphrodite

rare

Question 8

(Sex Reversal - XX males and XY females)

1. What occurs in these syndromes?

(in both XX and XY sex reversal, true hermaphrodites may also occur - can also get an intersex appearance to the genitalia)

Answer 8

1. both gonadal and phenotype sex agree - but are at oods with chromosomal sex

aka disorders of gonadal sex (cause gonadal sex at odds with chromosomal)

Question 9

(Sex Reversal)

(XX sex reversed males - XX Testicular DD)

1. what are these?
2. why sterile?
3. how common in humans?

(Ddx)

1-2. what happens? two options

Answer 9

1. have testes and are phenotypically male though sterile
2. XX germ cells can’t survive in testes
3. fairly - 1/20,000
4. transolcation of SRY to X or an autosome
5. mutation of a downstream gene in testis cascade that permits activity in absence of SRY

Question 10

(XY Sex Reversed Females - XY Gonadal Dysgenesis)

1. what is this?
2. in humans ovaries degenerate to what?
3. genetic cause unkown in what percentage of human cases?

(DDx)

1. what happens?

Answer 10

1. female phenotype an ovaries but chromosomally XY
2. streak gonads
3. 75%
4. deletion of Sry from the Y chromosome or mutation causing its inactiation (20 mutations in SRY have been desribed)

(doesn’t have to be SRY, mutation of various genes in testis determining cascae could give simlar phenotype)

Question 11

(SEX REVERSAL)

LOOK AT PICS ON p37

Question 12

(Androgen Based Disorders)

1. Genetic defects that decrease androgen action in genetic males or increase it in genetic females are the most frequently diagnosed causes of disorders in sexual differentiation in humans.

Question 13

(Androgen Based Disorders)

(Androgen Receptor Defects)

1. androgen receptor is product of what gene in humans?
2. What does complete deficiency (no AR) lead to?
3. Affected individuals are XX or XY? do they have testicles? how compare to normal females size wise?

Answer 13

1. X-linked
2. testicular feminization/complete androgen insensitivity (complete androgen insensitivy syndrome: CAIS)
3. XY, yes, phenotypically taller than females and have larger male teeth

Question 14

(Androgen Based Disorders)

(Androgen Receptor Defects)

1. No T-AR –> ?
2. No DHT-AR –> ?
3. Normal MIS –> ?
4. Testes are located where?

(Some mutations of the receptor cause only partial inactivation –> partial masculinization = variable phenotype

(partial androgen insensitivity syndrome: PAIS ~ 10% of androgen insensitivity cases are partial)

Answer 14

1. Wolffian duct regression (have T but it won’t work)
2. female external genitalia (have DHT but it can’t work)
3. Mullerian Duct regression (have MIS and MIS receptor so it does work)
4. inguinnally (occasionally labial)

Question 15

(5alpha-REductase Defects)

1. also part of testicular feminization syndrome
2. Have T but can’t make what?
3. normal androgen receptor –> can T function normally?
4. Patients are XY, have bilateral testes and normally virilized wolffian structures but these terminate where?
5. often the brain sex is what?
6. testes may be descended to where?
7. Very common in some inbred groups -in one New Guinea tribe affected children are not raised as male or female but assigned a third sex.

Increases in T after puberty can result in virilization and desire to change assigned sex to male.

LOOK AT PAGE 39

Answer 15

2. DHT
3. yes
4. at a blind vagina (the external genitalia is female)
5. male brain sex
6. labia majora