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Embryology of male reproductive system
- Retroperitoneal
- 7-8 gestational mo, testes descend thru inguinal canal
- Lymph drainage of testes goes into para-aortic lymph nodes in abdomen
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Layers of the testis
- Scrotum (skin)
- External spermatic fascia: extension of external oblique fascia
- Cremasteric fascia: extension of internal oblique fascia
- Internal spermatic fascia: extension of transversalis
- Tunica vaginalis: partietal and visceral
- Tunica albuginea: fibrous connective tissue, thickens posteriorly to form mediastinum testis
- Testicular lobules: divided by fibrous partition, contain seminiferous tubules
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Layers of seminiferous tubule
- lamina propria - containing myoid cells that contract tubules
- Leydig cells/interstitial cells: contain receptors for LH, produce testosterone
- basement membrane
- Germinal or seminiferous epithelium: Sertoli/Sustentacular cells and proliferative spermatogenic cells
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Sertoli cells
- Columnar cells that rest on basement membrane
- Elongated nucleus
- Support, protect, and nourish proliferative cells
- Secrete substances that regulate sperm production
- Phagocytic
- Protection of prolif cells from autoimmune attack
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basal and adluminal compartments
- basal compartment of Sertoli cells develop tight junctions during puberty, prevent transduate from reaching adluminal compartment
- blood-testis barrier: tightest blood-tissue barrier in mammals
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Spermatogenesis
- Spermatogenic cell = spermatogonium
- Division (MITOSIS) gives rise to one new germ cell (spermatogonium, resistant to radiation/chemo) and primary spermatocyte (committed cell)
- Primary spermatocyte (2n) -> 2 secondary spermatocytes
- Secondary spermatocyte (n) -> 2 spermatids
- Spermatids undergo spermiogenesis until mature (non-motile - not mature-motile until past epididymis)
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Length of spermatogenesis and spermiogenesis
What is spermiation?
- spermatogenesis: 60d - spermatogenic cells stay connected to each other thru cytoplasmic bridges
- spermiogenesis: 20d
- spermiation: release of 128mil sperm into duct system/day
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Sperm
- head - contains chromatin, acrosomal cap w/enzymes to digest ovum
- tail - specialized cilium, referred to as flagellum - ATP and dynein activity
- 35C optimal
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Maintaining temp for healthy sperm cells
- 35C
- pampiniform plexus of veins in scrotum dissipate heat
- cremaster muscle & dartos muscle superficially contract to increase temp
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components of spermatic duct system
- intratesticular ducts: straight tubules (Sertoli->simple cuboidal), rete testis (cimple cuboidal), efferent ducts (simple cuboidal ciliated/non-ciliated)
- epididymis: pseudostratified columnar epithelium, stereocilia, sperm can be stored up to a month
- vas (ductus) deferens: highly muscular (longitudinal and circular), pseudostratified, elastic fibers, adventitia
- ejaculatory duct - like vas deferens w/o muscle
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accessory glands
- 2 seminal vesicles - connects to vas deferens
- prostate
- two bulbourethral glands
- produce secretions added - 90% of ejaculate
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seminal vesicles
- lacy mucosa
- pseudostratified columnar epithelium
- secretion: PGs, fructose, fibrinogen, enzymes
- coagulate semen after ejaculation
- lamina propria rich in elastin
- 2 layers of smooth muscle
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prostate gland
- surrounds urethra @base of urinary bladder
- milky fluid: citrate, Ca2+, enzymes
- thru prostatic ducts
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Molecular mechanism of LH on Leydig cell
- LH binds to G-coupled protein receptor
- Adenylate cyclase-> increase cAMP, activation of PKA
- Phosphorylation, synthesis of testosterone
- cholesterol -> pregnenolone -> progesterone -> 17 alpha hydroxyprogesterone -> androstenedione -> testosterone
- Aromatase converts to estradiol (not in Leydig)
- 5 alpha reductase converts to dihydrotestosterone (not in Leydig)
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Testosterone distribution in plasma
- 3% free
- 30% bound to albumin
- 67% bound to SHBG (sex hormone binding globulin/adrogen binding protein) - synthesized primarily in the liver
- SHBG: prevent steroid diffusion into cells, increase half-life
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GnRH secretion
- pulsatile; causes LH, FSH release to be pulsatile also
- difficult to study because it's released in small amts in portal circulation, degraded quickly
- Inhibin synth by Sertoli/granulosa cells inhibits FSH secretion
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Fetal male differentiation
- Testes secrete testosterone when stim. by LH @16wks gestation
- Wolffian ducts differentiate into seminal vesicles, epididymes, vas deferens
- Sertoli cells secrete Mullerian Inhibiting Factor
- External development of penis and prostate require 5 alpha reductase to convert testosterone to DHT
- Lack of 5 alpha reductase = ambiguous external genitalia
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Hypothalamus-Pituitary-Testes pathway
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Role of SRY
- required for testicular development
- testes make testosterone to stimulate Wolffian ducts, DHT stimulates development of male external genitalia, MIF would normally inhibit development of female internal genitalia
- XY individual w/ SRY KO = phenotypic female
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Path of ureter in male
- Under-over-under
- Under testicular vessels
- Over common iliac vessels
- Under vas deferens
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What glands are located at the deep perineal space/pouch?
Bulbourethral glands
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What is testicular feminization syndrome?
- Lack of androgen receptors
- Gonads still develop into testes (undescended), but labia majora will form
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What is required for spermatogenesis?
- LH needed for testosterone secretion
- FSH needed for normal Sertoli cell fx
- Not required: DHT
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Inguinal triangle boundaries
- Inferior epigastric vessels
- Rectus abdominis
- Inguinal ligament
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Andropause
Decreases in muscle mass, libido, appetite, bone formation
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Indirect inguinal hernia
Failure of processus vaginalis to close
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Finasteride and dutasteride
- 5-alpha reductase inhibitor (type 2)
- Prevent conversion of testosterone to DHT
- Treatment of BPH, causes prostate to undergo atrophy/apoptosis
- dutasteride inhibits type 1 and 2
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sildenafil
- 5-phosphodiesterase inhibitor (PDE-5 inhibitor)
- causes cGMP to remain elevated for longer than usual
- NO has half life of seconds
- half-life of 4hr, 40% bioavailability
- helicine artery dilation
- SE: headache, flushing, nasal congestion, color vision disturbance
- No erection without arousal; cGMP should only be produced during arousal
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Micturition events
- Sensory afferent signaling of bladder fullness to CNS
- CNS modulated external sphincter relaxation
- internal urethra/bladder neck relaxation
- CNS-mediated increase in detrusor contractility
- Urination
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Side effect of anti-cholingerics
- Overflow incontinence
- (Inhibition of normal bladder emptying)
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Incomplete distal closure of urethral folds
Hypospadias
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Urinary changes with aging
- Decreased bladder capacity and force of contractions
- decreased ability to postpone voiding
- decreased urethral compliance
- Weakening of pelvic support muscles
- increased postvoid residual volume
- involuntary bladder contractions
- nocturia 1-2x/night
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Parasympathetic tone of bladder
- muscarinic receptors control parasymp tone of detrusor muscle
- M2 receptors inhibit cAMP-mediated smooth muscle relaxation
- M3 receptors directly cause contraction
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Estrogen deficiency: effect on bladder
- reduced effectiveness of internal and external sphincters that have estrogen receptors
- predisposition to urethritis, trigonitis, cystitis
- vaginal atrophy
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TCA antidepressants: examples, mechs, and SE
- amitriptyline/imipramine
- indirectly-acting sympathomimetic, incr. [NE, 5HT]
- SE: anticholingeric, treats urinary incontinence - blocks actions of ACh @ muscarinic receptors
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desmopressin
- treatment for nocturnal enuresis
- DDAVP, reduces urine production
- SE: hyponatremia
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types of incontinence
- overflow: partial voiding when bladder is full
- stress: common in women, caused by pressure when laughing, sneezing, etc
- urge: detrusor hypersensitivity
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tamsusolin
- alpha-1 adrenergic antagonist, blocks contractile actions of NE on smooth muscle of internal sphincter
- SE: orthostatic hypotension, can cause retrograde ejaculation
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Male sexual response
- alpha adrenergics on helicine artery maintain vascular tone (non-aroused)
- sympathetics stimulate smooth muscle in vas deferens, capsule of seminal vesicle, capsule/fibromuscular stroma of prostate during ejaculation
- Parasympathetic stimulation -> release ACh, NO -> erection
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Penis: somatic and autonomic
- somatic: pudendal nerve, dorsal nerve of the penis
- for bulbospongious and ischiocavernosus, the perineal branch of the pudendal nerve
- autonomic: cavernous nerve (innervating corpus cavernosum) from the prostatic plexus
- sympathetic stimulation of cavernous nerve closes internal urethral sphincter, prevent retrograde ejaculation
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oxybutnin
- blocks ACh binding to muscarinic receptors
- increases bladder capacity
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tolterodine
- antagonist at M3 receptors
- most effective for urge incontinence
- SE: dry mouth, constipation
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