05 - Disorders Associated with AMH/MIS

Question 1

(Persistent Mullerian Duct Syndrome in Males)

1. A heterogenous disorder resulting in what?
2. Affected individuals are relatively normal males thay may have cryporchidism, but also have what?
3. This can be the result of either what or what?
4. Most human cases are autosomal recessive… so only what are affected?

Answer 1

1. male pseudohermaphroditism
2. a uterus and oviducts
3. deficiency in MIS or end-organ unresponsiveness

(ih humans see both etiologies… some have no MIS, some have normal MIS and a receptor defect)

4. homozygous males (not heterozygous males or homozygous females)

Question 2

(Persistent Mullerian Duct Syndrome in Males)

Cryptorchidism in patients with PMDA may have different mechanisms for failure of testicular descent than those previously discussed

1. how are these different?
2. What happens most often?
3. Is often unilateral… why?
4. bilateral cryptorchidism also occurs less frequently… how does it happen?

Answer 2

1. testis tightly linked to retained oviducts (phenotype depends on how mobile these are)
2. they are fairly mobile and the testes descend, dragging the oviducts and part of the uterus into inguinal canal.
3. 1 testis enters dragging everything along, the opposite testis attached to associated oviduct pulled towar midline and can’t descend
4. round ligament restrains the uterus and oviducts (and thus the testes)

Question 3

(MIS Excesses)

1. Exposure of female fetuses to MIS during early embryogenesis causes what? why?
2. Immature ovaries exposed to MIS have reduced aromatase activity and hence produce more what?

Answer 3

1. regression or agenesis of Mullerian structures and later potentially an “endocrine sex reversal” of the ovaries (because MIS inhibits aromatase)
2. testosterone (it builds up cause they can’t convert to testosterone)

(look at pic on 40)

Question 4

(Syndromes assocaiated with aneuploidy)

(Turners Syndrome)

1. chromosome structure?
2. how common?
3. tend to have what?
4. Ovaries are normal early in gestation but have an accelerated rate of what?

Answer 4

1. single X chromosome (in humans 45,XO)
2. most common in humans (1/100 conception… but 98-99 abort so 1/10,000)
3. streak gonads
4. atresia (the XO germ cells are lost at an increased rate as they enter meiosis)

Question 5

(Syndromes assocaiated with aneuploidy)

(Turners Syndrome)

1. By the time of birth there are few oocytes left in the ovaries… why?
2. Why are there few secondary sex characteristics?

Answer 5

1. two x chromosomes are functional in femal germ cells during oogenesis, this is required for normal completion
2. ovaries of XO individuals degenerate to “streaks” of fibrous connective tissue, unable to generate follicles or perform sterod synth

(Most of these individuals have a juvenile repro tract and 97% have primary amenorrhea)

Question 6

(Syndromes assocaiated with aneuploidy)

(Turners Syndrome)

1. the cause of most Turner’s syndrome cases is what?
2. what exactly?
3. In what percentage of human XO individuals is the x chromosome of maternal origin?
4. What animal species gets this most often?

Answer 6

1. paternal (defective sperm)
2. sperm devoid of a sex chromosome due to erroris in meisosi or mitosis
3. 80%
4. horses (short, longer ears, small ovaries and uterus)

Question 7

(Kleinfelter’s Syndrome)

1. what is this?
2. affects how many newbord males?
3. more mother or father’s fault?
4. germ cells present in lower numbers during infancy… losses accelerate when? acompanied by what?
5. What do these boys look like?

Answer 7

1. males have extra X
2. 1/250 - 1/1,000 (47, XXY)
3. equal (errors in meiosis)
4. puberty (degeneration of seminiferous tubules)
5. tall, have delayed puberty, low testosterone production, sparse pubic and body hair, small penis (all secondary to reduced testosterone)

Question 8

(Kleinfelter’s Syndrome - cont)

1. following when are males usually sterile?
2. What do testes look like? seminiferous tubules?
3. Do they form Barr body’s?
4. So why is there any effect?
5. occur in other species?

Answer 8

1. puberty
2. small, atrophied, few or no germ cells; atrophied
3. yes
4. so X-linked genes escape X-inacivation
5. occasionally….