Male Reproductive Physiology (Week 6--Lerman) Flashcards
What is hypospadias?
Congenital defect where urethra comes out the ventral side of the penis rather than the end
(also hooded foreskin and penis curved?)
What are the three things that contribute to gender or sexual differentiation?
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!
What is the sex-determining part of the Y chromosome?
SRY region
When do the testes form in the fetus?
6 weeks
What do Sertoli cells do?
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)
Mullerian inhibitory factor (MIF)
Secreted by Sertoli cells
Tells Mullerian (Female) duct to degenerate during development
What must happen for normal male sexual differentiation?
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)
What determines whether the Mullerian or Wolffian duct develops?
Everyone starts with both ducts!
If you have MIF and androgens, keep male Wolffian (Mesonephric)
If have no MIF or androgens, keep Mullerian (Paramesonephric)
If you’re unsure of the sex of the baby, where do you look?
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
Does the brain respond to sex hormones?
Yes, the brain responds to increased levels of testosterone (behavioral differences, etc)
What remains after the Mullerian duct has regressed?
Appendix testis
Prostatic utricle
(males have these)
What remains after the Wolffian duct has regressed?
Epoophron
Gartner’s duct
(females have these)
Intersex state
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)
Testicular Feminization Syndrome (Androgen Insensitivity Syndrome)
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
What are the problems with intraabdominal testes?
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
Congenital Adrenal Hyperplasia (CAH)
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
What happens at puberty?
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
What physical changes occur in boys at puberty?
First, testicles get larger (this can happen asymmetrically)
Pubic hair
Penile growth
Somatic growth
Voice changes (larynx, vocal cords)
Spermatogenesis
At what ages and what percentages do you see undescended testicles?
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
What would cause testicles not to descend?
Prune belly syndrome (no abdominal musculature, looks like huge hernia) means you have no abdominal pressure so you can’t squeeze the testes down
Spermatocoel or epididymal cyst
Diverticulum/pocket in epididymis
Usually harmless, don’t operate because could cause damage to rest of duct
How do you know when it’s safe to have unprotected sex (for birth control) after a vasectomy?
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
What are some causes of male infertility?
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
Erectile dysfunction
Psychogenic
Neuropathic (spinal cord injury, diabetic neuropathy)
Trauma/scarring (Peyroine’s Disease, priapism)
Vasculogenic (most common)
Treatment of ED
Oral medication (viagra inhibits cGMP breakdown)
Intracorporeal injection (vasodilation)
Penile prosthesis
Vacuum Erection Device (was big in the 60’s..)
Andropause
Gradual decrease in serum testosterone with aging
Decrease in bone formation, muscle mass, growth of facial hair, appetite, libido
Can you give testosterone replacement to treat andropause?
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
