Male Reproductive Physiology (Week 6--Lerman)

Question 1

What is hypospadias?

Answer 1

Congenital defect where urethra comes out the ventral side of the penis rather than the end

(also hooded foreskin and penis curved?)

Question 2

What are the three things that contribute to gender or sexual differentiation?

Answer 2

1) Genetic sex (XX vs XY)
2) Gonadal sex (ovaries vs testes)
3) Phenotypic sex (internal genital tract vs external genitalia)

These three things are not always consistent!

Question 3

What is the sex-determining part of the Y chromosome?

Answer 3

SRY region

Question 4

When do the testes form in the fetus?

Answer 4

6 weeks

Question 5

What do Sertoli cells do?

Answer 5

1) Support, protect, nourish sperm (make nutrients available from interstitial space/capillaries)
2) Secrete substances to regulate sperm production
3) Phagocytose debris/residue
4) Protect proliferative cells from autoimmune attack
5) Secrete Mullerian Inhibiting Factor (MIF)

Note: aromatase in Sertoli cells turns T and androstenedione into estrogen (??)

Note: Sertoli cells secrete inhibin (negative feedback to both anterior pituitary and hypothalamus)

Question 6

Mullerian inhibitory factor (MIF)

Answer 6

Secreted by Sertoli cells

Tells Mullerian (Female) duct to degenerate during development

Question 7

What must happen for normal male sexual differentiation?

Answer 7

1) Sertoli cells secrete MIF which causes degeneration of Mullerian (Female) duct
2) Leydig cells secrete testosterone which causes Wolffian (Male) duct to differentiate
3) Paracrine action of testosterone causes seminal vesicles, vas deferens, epididymis to develop (internal)
4) DHT acts on receptors at tissues to cause prostate, penis, and scrotum to develop (external)

Question 8

What determines whether the Mullerian or Wolffian duct develops?

Answer 8

Everyone starts with both ducts!

If you have MIF and androgens, keep male Wolffian (Mesonephric)

If have no MIF or androgens, keep Mullerian (Paramesonephric)

Question 9

If you’re unsure of the sex of the baby, where do you look?

Answer 9

1) See if there is Y chromosome, and specifically SRY region
2) Look for gonads using ultrasound, laparoscopy (can see intraabdominal testicle this way)
3) Look for hormones: give HCG to stimulate Leydig cells to secrete testosterone–if have hidden testicle then T will increase

Question 10

Does the brain respond to sex hormones?

Answer 10

Yes, the brain responds to increased levels of testosterone (behavioral differences, etc)

Question 11

What remains after the Mullerian duct has regressed?

Answer 11

Appendix testis

Prostatic utricle

(males have these)

Question 12

What remains after the Wolffian duct has regressed?

Answer 12

Epoophron

Gartner’s duct

(females have these)

Question 13

Intersex state

Answer 13

Significint inconsistency or inefficiency in one of the ten determinants of sexual differentiation

(chromosome, TDF/SRY, gonads, paracrine hormones, Mullerian ducts, Wolffian ducts, endocrine hormone, urogenital sinus, external genitalia, secondary sexual characteristics, brain)

Question 14

Testicular Feminization Syndrome (Androgen Insensitivity Syndrome)

Answer 14

Eva from Nip/Tuck!

“Male” patient born with XY and SRY so makes testicles, but testicles do NOT descend

Mutation in androgen receptor (AR), so testosterone cannot signal to make normal Wolffian duct and DHT cannot signal to make penis, scrotum, prostate, secondary sexual characteristics

Result is FEMALE looking baby, then “default” of blind shallow vagina, clitoris, labia majora/minora, breasts, less pubic/axillary hair, amenorrhea

At puberty, LH surge obviously can’t stimulate ovulation because no ovaries (MIF is present and worked), so this “girl” has no periods and must now make gender decision

Muscles androgenized, shallow vagina

Question 15

What are the problems with intraabdominal testes?

Answer 15

Temperature in body too warm for testes (they like to be 1-2 degrees below body temp), so can be infertile bc sperm production messed up

More likely to develop cancer

Note: testosterone secreting function of testes is fine

Question 16

Congenital Adrenal Hyperplasia (CAH)

Answer 16

Reminder: deficiency in 21-hydroxylase so no cortisol made and too much testosterone made; when stressful situation, will not be able to respond appropriately

Patient looks like boy with small curved penis and opening at bottom, but is ACTUALLY female that was hypervirilized (example of how hypospadias can be life-threatening); patient is XX and internal structures are female, but brain bathed in testosterone can cause aggresstion, etc

CAH is recessive, and if one child has CAH thre is 1/8 chance that second one will have CAH

Should feel for testicles, and if not there, be suspicious. If testicles there, then is probably just hypospadias

Question 17

What happens at puberty?

Answer 17

Before puberty, HPG axis is very sensitive to negative feedback of testosterone and estradiol and GnRH secretion is inhibited.

At puberty, changes in CNS cause GnRH secretion to increase pulse frequency and be less sensitive to negative feedback of testosterone and estradiol, so LH and FSH secretion increases –> Leydig cells make more testosterone (bc of LH) and Sertoli cells release factors to “nurse” development of spermatogonia (bc of FSH) –> gonads develop more

Question 18

What physical changes occur in boys at puberty?

Answer 18

First, testicles get larger (this can happen asymmetrically)

Pubic hair

Penile growth

Somatic growth

Voice changes (larynx, vocal cords)

Spermatogenesis

Question 19

At what ages and what percentages do you see undescended testicles?

Answer 19

30% of premature babies (32 weeks or earlier) have undescended testicle

3% of term infants have undescended testicle

1% of 1 year olds have undescended testicle

Note: clinically, if baby boy is 6 months old and no testes descended, Dr. Lerman will surgically bring testes down

Question 20

What would cause testicles not to descend?

Answer 20

Prune belly syndrome (no abdominal musculature, looks like huge hernia) means you have no abdominal pressure so you can’t squeeze the testes down

Question 21

Spermatocoel or epididymal cyst

Answer 21

Diverticulum/pocket in epididymis

Usually harmless, don’t operate because could cause damage to rest of duct

Question 22

How do you know when it’s safe to have unprotected sex (for birth control) after a vasectomy?

Answer 22

Do semen analysis to make sure there is not active sperm in there

Note: after vasectomy still have sperm in second half of tube!

Note: semen volume will be the same because sperm are only 10% of volume

Question 23

What are some causes of male infertility?

Answer 23

Vasectomy

Sertoli Cell Only Syndrome (genetic or acquired via orchitis, alcohol, toxins)

Bilateral inguinal hernia repair in baby cut vas deferens (iatrogenic)

Cystic Fibrosis causes congenital absence of vas deferens

Retrograde ejaculation

Question 24

Erectile dysfunction

Answer 24

Psychogenic

Neuropathic (spinal cord injury, diabetic neuropathy)

Trauma/scarring (Peyroine’s Disease, priapism)

Vasculogenic (most common)

Question 25

Treatment of ED

Answer 25

Oral medication (viagra inhibits cGMP breakdown)

Intracorporeal injection (vasodilation)

Penile prosthesis

Vacuum Erection Device (was big in the 60’s..)

Question 26

Andropause

Answer 26

Gradual decrease in serum testosterone with aging

Decrease in bone formation, muscle mass, growth of facial hair, appetite, libido

Question 27

Can you give testosterone replacement to treat andropause?

Answer 27

Testosterone replacement can be given as monthly IM injection or transdermal patch

Yes, but first must rule out prostate cancer bc don’t want to give it to someone with testosterone-dependent prostate cancer