03 - Inguinoscrotal Descent

Question 1

(Gonadal Descent)

1. onlly occurs in mammals
2. in species where it does occur it requires what for successful spermatogenesis?
3. not known why this isnt the case for all mammals - what is an animal that doesen’t have external testes?

Answer 1

2. lower temp (in scrotum)
3. elephants

Question 2

(Gonadal Descent)

(Biphasic model)

1-2 What are the two stages?

Answer 2

1. transabdominal descent
2. inguino-scrotal descent

Question 3

(Gonadal Descent)

(Biphasic model)

(Transabdominal Testicular Descent)

1. In the early embryo the gonad on the urogenital ridge is anchored to the body wall by what?
2. What is the caudal suspensory ligament called?

connectss the gonad to the future what?

3. During embryonic development the crainal suspensory ligament regresses in what sex? mediated by what?
4. What happens to gubernaculum in females?

Answer 3

1. cranial and caudal suspensory ligaments
2. the gubernaculum (or genito-inguinal ligament)

future inguinal region

3. the male (not the female); testosterone
4. regress to long thin band of tissue

Question 4

(Gonadal Descent)

(Transabdominal Testicular Descent)

1. In the male the gubernaculum thickens - forming what as the cranial suspensory ligament regresses?

this anchors what to what?

2. What hormone is responsible for this gubernacular growth?
3. What does INSL3 bind to?

Answer 4

1. the gubernacular bulb

the testicle to the internal inguinal region

2. Insulin like factor 3 (INSL3) (secreted by Leydig cells of fetal testis)
3. its receptor, GREAT (G protein-copuled receptor affecting testicular descent) (aka LGR8)

(It appears that the effect of INSL3 can be augmented by MIS and testosterone but that these are of relatively minor importance. So ratherthan the testicle being pulled across the abdominal cavity by the gubernaculum, it is anchored to the inguinal region by the gubernaculum while the abdomen of the embryo elongates.)

Question 5

(Gonadal Descent)

1. During development female gonad is relatively tightly bound to what?

male?

(Final position of ovary varies with species….)

2. which remain close to dorsal body wall?
3. intermediate?
4. loose

Answer 5

1. dorsal body wall

inguinal region

2. rodents, dogs and cats
3. mare
4. cow

Question 6

(H.i.b. Inguinoscrotal Descent)

1. While gubernaculum thickens it also grows the internal inguinal ring and canal… moves to what?
2. Also hollows out to allow what to go with it?
3. Which muscle forms from outer rim of gubernaculum?

Answer 6

1. through the external inguinal ring into the future scrotum
2. out-pouching of peritoneum (processus vaginalis) - (will form vaginal tunic)
3. cremaster muscle

Question 7

(Inguinoscrotal Descent - 2)

1. Inguinoscrotal movement of gubernaculum controlled by androgens via what?
2. spinal nucleus of GFN is sexually dimorphic in rodents - more cell in females or males? cutting causes what?
3. Under the influence of what does the GFN release that binds to gubernaculum during outgrowth?

what does this cause gubernaculum to do?

androgen also plays role in gubernaculum responding to CGRP

Answer 7

1. genitofemoral nerve (GFN)
2. males; inhibits migration of gubernaculum into scrotum
3. calcitonin gene-related peptide (CGRP) - a neurotransmitter

causes growth of tip and movement through inguinal canal into scrotum

Question 8

(Inguinoscrotal Descent - 3)

1. Some time after it complete inguinosacral migration (timing depends on species), the bulky gubernaculum regresses… allowing what?
2. What two factors cause the testicle to enter the inguinal canal and scrotum?

Answer 8

1. the epididymis and testicle to enter the scrotum
2. traction from regressing gubernaculum; increasing intraabdominal pressure resutling from enlargement of other organs

Question 9

(H.ii. Timing of Testicular Descent)

(say when testicular descent occurs)

1. ram and bull
2. boar
3. stallion
4. tom
5. dog
6. human

Answer 9

1. half way through gestation
2. last quarter of gestation
3. just before birth to two weeks postnatally
4. usually by birth (should be easily palpable at first vaccination (6-8 weeks))
5. 10-14 days of age, may not be fully in scrotum til 6-8 weeks
6. prior to birth

Question 10

(H.iii. Cryptorchidism)

1. what is this?
2. most common genital anomaly in males at birth - is there one cause?
3. are more cases inguinally or abdominally related?

4-5. What are two more possible causes?

6. Aberrant migration of the gubernaculum, with insertion in the scrotal neck or side rather than base, has also been reported

Answer 10

1. failure of one (unilateral) or both (bilateral) testicles to descend into the scrotum at the normal time
2. no - it’s a complex process - therefore multiple etiologies
3. inguinally (case can be made for defect in androgen pathway - perhaps with GFN) (suspected in human to be defect in prenatal androgen secretion)
4. mechanical (abdominal wall defect - messed up pressure)
5. neurological (GFN/CGRP anomalies)

Question 11

(Cryptorchidism - Prevalence)

(give percentage)

NEVERMIND - HE IS NOT GOING TO ASK THIS!

1. bull
2. dog
3. cat
4. horse
5. human

Answer 11

1. 0.17% (increased in polled herefors and shorthorns)
2. 0.8-1.5% (higher in purebreds and toys)
3. 1.3% (in study of feral cats)
4. 2-8%
5. 4-5% at birth… 2% by 6-12 months

Question 13

(H.iii.b - Problems involved with cryptorchidism)

1-2. name two

(heritability)

3. is it a simple genetic trait?
4. in most speceis thought to be what?

Answer 13

1. infertility
2. tumor formation (Sertoli cell tumor in dogs) (seminoma in humans)
3. no (has large genetic component)
4. autosomal recessive (or dominant with incomplete penetrance) - (don’t use affected animals for breeding)

Question 14

(I. Non-reproductive organ sexual dimorphisms)

READ THIS

All organs and tissues likely exhibit sexual dimorphism; to date the most widely studied organ in this regard is the brain. Behavioral differences between the sexes, particularly in social and reproductive settings, triggered extensive studies of brain structure and function; and while most until recently have focused on regions associated with reproduction and reproductive behaviors, it is likely that the differences involve every brain cell to some extent.

Numerous sexual dimorphisms in the brain have now been demonstrated, some highly phylogenetically conserved from insects to mammals. They vary from gross anatomical differences, through ultrastructure, biochemistry and molecular mechanisms. Among other things the size of specific areas of the brain may vary by sex, as may clusters of neurones (nuclei), the projections and connections between different areas, concentrations and distributions of enzymes, neurotransmitters and their receptors, and the receptors for steroid hormones.

Question 15

(Non-reproductive organ sexual dimorphisms)

The brain areas that will become sexually dimorphic start out as monomorphic in early development and differences can subsequently arise thorugh 3 braod mechanisms…

1-3. name them

Answer 15

1. hormone exposure (gonadal steroids testosterone and estrogen)
2. genetic (chormosomal) constituion of cell (XX or XY)
3. epigenetic effects (changes associated with differential methylation of DNA/acetylation of histones

Question 16

(I. Non-Reproductive organ sexual dimorphisms)

1. For brain sexual dimorphisms in mammals, particularly for those associated with reproductive function and behaviors, the most important influence is what?
2. When does this exposure occur? occurs in what? due to what?
3. first testosterone surge sets what?
4. second sets what?

Answer 16

1. hormone exposure (ie brain sex largely set by steroid exposure)
2. “perinatal sensitive period” (late fetal to early neonatal), occurs in males, due to second surge of testosterone production from the testes

(This is the “classical” explanation in mammals and even with emerging information on alternative causes this hormone exposure is still by far the dominant influence on setting somatic sex differences of mammals, including brain sex)

3. phenotypic sex
4. brain sex

Question 17

(I. Non-Reproductive Organ Sexual Dimorphisms)

(Cell Life vs. Death)

1. Sexual dimorphism in the size of different brain nuclei (groups of cells)in the hypothalamus involved in reproductive function is the result of what?
2. Nuclei start out same… what rescues neurons in males? can it also destroy in males?

Answer 17

1. selective cell death
2. steroid exposure (so males have larger nucleus in these areas); yes (the females then are larger)

(steroids don’t just affect those cells that have receptors for them (only a fraction of brain cells), also effectcells lying in close proximity to these primary targets with which they have a connection)

Question 18

(I. Non-Reproductive Organ Sexual Dimorphisms)

Which Hormone is actually doing the work?
The testes secrete testosterone so the action has to be due to testosterone… right? Not necessarily: Depending on species (and perhaps region of the brain and/or neuron type) the action of testosterone on the brain may be exerted directly via androgen receptors or the testosterone may only be effective after it is aromatized locally (in the brain)to estrogen which then acts on estrogen receptor (alpha or beta - usually alpha). In rodents the vast majority of testosterone actions to masculinize the brain appear to depend on its local conversion to estrogen and there is only a very minor role for direct action oftestosterone acting through androgen receptorsin setting organizational brain patterns. In human/primates evidence indicates that direct actions of testosterone acting via androgen receptors are much more important. Most other species haven’t been looked at.

Question 19

(I. Non-Reproductive Organ Sexual Dimorphisms)

(Organizational vs Activational Dimorphisms)

1. so far been talking about organization/permanent differences - these regarded as developmental and permanent….

others are regarded as reversible or transient and occur in response to hormone exposure later in life - these are called what?

Answer 19

1. activational

(Note that some developmental changes will alter the response to an activational hormone exposure - males might show high libido in response to testosterone)

Question 20

(I. Non-Reproductive Organ Sexual Dimorphisms)

(Brain sex and other somatic sexual dimorphisms: It isn’t all Hormones)

1. several sexual dimorphisms appear to be the result of direct genetic influences or epigenetics

(genetic (chromosomal) constitution of the cell)

(the direct effect of the cell being XX or XY)

1. the genes are uniquely expressed in one sex (what in males?)
2. They are expressed higher in one sex due to dosage effects - like what in females?

Answer 20

1. non-pseudoautosomal region Y chromosome genes occur only in males
2. X-linked genes that escape inactivation

Question 21

(I. Non-Reproductive Organ Sexual Dimorphisms)

(Brain sex and other somatic sexual dimorphisms: It isn’t all Hormones)

(Epigenetic Effects)

1. Particulary here are changes associated with what?
2. they are imprinted (different expression of what?
3. sex-specific regions of heterochromatin that exert epigenetic effects on other parts of the genome

Answer 21

1. with different methylation of DNA/acetylation of histones
2. Xp vs Xm