Testis and Male Reproductive Tract Flashcards
Functions of the Testes
-
Exocrine secretion of male gametes and fluids allowing their passage from the testis.
- “Holocrine” fashion
- Major site of endocrine secretion of androgens
- Testosterone - Leydig cells
- DHT
Testes
Development
- Formed in the abdominal cavity
- Descend prenatally: abdominal cavity ⇒ inguinal canal ⇒ scrotum.
- Carries along an out-pocketing of peritoneum ⇒ processus vaginalis
- This loses connection with peritoneal cavity ⇒ tunica vaginalis
- overlies the anterior and lateral surfaces of the testis
Cryptorchidism
Failure of the testis to descend.
- Can result in sterility if not surgically corrected during childhood.
- Testosterone production maintained resulting in normal male secondary sex characteristics.
- Associated with increased incidence of testicular cancer.
Testes
Temperature Regulation
Testis suspended within scrotal sac and maintained at 2-3° below core body temperature.
Required for spermatogenesis.
Methods of temperature regulation include:
-
Contraction of cremaster muscle
- pulls testes towards inguinal canal
- increases temperature
- cremaster is skeletal muscle not under voluntary control
-
Pampiniform plexus surrounds testicular artery
- forms counter-current heat exchange system
- cools arterial blood before it enters testis
-
Tunica dartos of hypodermis contains longitudinal smooth muscle
- contracts in response to cold
- wrinkles scrotal skin drawing testes towards body
-
Scrotal skin
- thin and hairy
- contains sebaceous and sweat glands
- little or no subcutaneous adipose tissue
- scrotal sweating and thin scrotal wall dissipates heat
Organization of the Testis
-
Tunica albuginea
- thick dense irregular fibrous CT capsule covering testis
- CT septa extend inward dividing testis into ~ 250 pyramidal lobules
- each lobule with 1-4 seminiferous tubules
- covered partially by mesothelium of visceral layer of tunica vaginalis
-
Mediastinum testis
- Thickened area of tunica albuginea at posterior surface
- supports nerves, vessels, and ducts including rete testis
- anastomosing set of channels directing spermatozoa out of testis
-
Tunica vasculosa
- innermost part of the tunica albuginea
- loose CT
- contains numerous blood vessels, nerves, and lymphatics
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Tunica Vaginalis
- Closed sac lined by mesothelium
- Parietal layer lines the wall of the sac
- Visceral layer covers part of testis & part of epididymis
- In direct contact w/ tunica albuginea
Seminiferous Tubules
Site of spermatozoa production.
- U-shaped tubule which starts and ends in mediastinum
- Lined by seminiferous epithelium
- Unusual & complex stratified epithelium
- Surrounded by tunica propria
- collagen fibrils
- several layers of myoepithelial cells ⇒ myoid cells
- lie just outside thick basal lamina
- constraction assists spermatozoa/fluid movement
-
Pre-pubescent seminiferous “tubules”
- Contains cords with no lumen
- Two cell types
-
Gonocytes ⇒ precursors of spermatogonia
- round with cental spherical nuclei
- Sertoli-like cells
-
Gonocytes ⇒ precursors of spermatogonia
-
Post-pubescent seminiferous tubules
- Contains supportive sertoli cells
- Spermatogenic cells found in mosaic pattern
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Sertoli Cell
Functions
- Physically support spermatogenic cells
- Control movement of spermatogenic cells through seminiferous epithelium
- Mediate movement of steroids and metabolites
-
Secretory:
-
Androgen-binding protein
- concentrates testosterone in seminiferous epithelium and proximal genital duct system
-
Estradiol
- regulation of steroid production by Leydig cells
-
Inhibin
- regulation of gonadotropin release by pituitary gland
- Substances that nourish and facilitate transport of spermatozoa
-
Androgen-binding protein
- Phagocytize degenerating spermatogenic cells and residual bodies
- Secretes fluid that pushes sperm out of the testis
- During embryogenesis, secretes Mullerian-inhibiting factor (MIF) aka anti-Mullerian hormone (AMH)
- suppresses development of the female reproductive tract
Sertoli Cell
Structure
-
Columnar cells which span entire height of seminiferous epithelium
- Basal lamina ⇒ tubule lumen
- Complex lateral and apical processes
-
Euchromatic nucleus with prominent nucleolus
- ovoid to triangular with 1-2 deep folds
- basally located
- Adjacent sertoli cells & spermatogonia joined via special junctional complexes
- junctions located near the basal end of lateral plasma membranes
- forms blood-testis barrier
- forms basal & adluminal compartments of seminiferous epithelium
- Extensive infoldings of lateral plasma membrane
- Contain inclusion bodies of Charcot-Böttcher
- slender crystalloid composed of filament bundles
- Do not proliferate
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Sertoli Cell
Junctional Complexes
Adjacent sertoli cells joined via unique junctional complexes to form the blood-testis barrier.
- Many close appositions of adjacent membranes form an extremely tight junction
- Flattened cisternae of SER parallel to membranes
- Hexagonally packed actin filament bundles between SER cisternae and membranes
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Blood Testis Barrier
- Formed via Sertoli cell junctional complexes
- Seminiferous epithelium divided into two compartments:
-
Basal compartment
- contains spermatogonia and young primary spermatocytes
- developing spermatocytes move between Sertoli cells despite junctions to reach next compartment
-
Adluminal compartment
- contains all other stages of spermatogenesis
- where meiosis and spermiogenesis occurs
-
Basal compartment
- Forms unique microenvironments
-
Restricts movement of molecules (specifically Ab) from surronding CT into adluminal compartment
- Protects late stage spermatogenic cells from immune attack
- Failure of blood-testis barrier can result in infertility
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Spermatogenic Cells
Spermatogenic cells undergo mitosis then meiosis to form spermatozoa.
Four major cell types in spermatogenic lineage:
- Spermatogonia
- Spermatocytes
- Spermatids
- Spermatozoa
Meiosis produces four haploid spermatids from each primary spermatocyte.
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Spermatogonia
- Small primitive germ cells
- Located next to basal lamina
- Enveloped apically by Sertoli cells
- Stem cells of male germ line
- Divide via mitosis after puberty and some differentiate into:
-
Dark type A spermatogonia
- dark slightly flattened nuceli
- usually quiescent
- occasionally divide via mitosis to reproduce themselves or form type A spermatogonia
-
Pale type A spermatogonia
- pale slightly flattened nuclei
- divide via mitosis to reproduce themselves or form pale type B spermatogonia
-
Type B spermatogonia
- round nuclei
- divide via mitosis to reproduce themselves or formprimary spermatocytes
- cells are commited to becoming sperm at this stage
-
Dark type A spermatogonia
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Primary Spermatocytes
- Undergo meiosis I
- Largest spermatogenic cells
- Nuclei with condensing chromosomes at various stages of meiotic division
- Prophase longest at ~ 22 days and most found in this stage
- Daughter cells are secondary spermatocytes
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Secondary Spermatocytes
- Divide rapidly therefore difficult to find in sections
-
Undergoes meiosis II
- Reduces DNA content and chromosome number to 1N
- Daughter cells are spermatids
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Spermatids
- Nuclei with highly condensed chromatin
- Located near lumen of tubule
- Do not divide
-
Early spermatids
- recently formed
- small round cells with round nuclei
-
Late spermatids
- look more like mature sperm
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Spermiogenesis
Golgi Phase
The morphological differentiation of spermatids into spermatozoa.
Can be divided into four phases:
Stage 1: Golgi Phase
- PAS+ granules accumulate in Golgi complex and coalesce
- Forms a single acrosomal granule within acrosomal vesicle
- Vesicle positioned at anterior pole of nucleus
- Centrioles migrate to opposite pole
- Distal centriole forms presumptive flagellum with 9+2 microtubule structure
- Constitues axoneme of sperm tail
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Spermiogenesis
Cap or Early Acrosomal Phase
The morphological differentiation of spermatids into spermatozoa.
Can be divided into four phases:
Stage 2: Cap or Early Acrosomal Phase
- Acrosomal vesical flattens over nucleus forming acrosomal cap
- contains hydrolytic enzymes needed for penetration of zona pellucida of ovum
- released during acrosome reaction of fertilization
- Nuclear evelope in contact with cap looses nuclear pores and thickens
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Spermiogenesis
Late Acrosomal Phase
The morphological differentiation of spermatids into spermatozoa.
Can be divided into four phases:
Stage 3: Late Acrosomal Phase
- Spermatid rotates so acrosome basal and developing tail luminal
- Nucleus flattens and elongates displacing cytoplasm posteriorly
- Cytoplasmic microtubules organize into cylindrical manchette
- temporarily sequesters proteins needed for elongation of tail
- Centrioles approach nucleus and form connecting piece/neck region uniting nucleus with flagellum
- 9 outer dense fibers (ODF) develop from modified centrioles
- Mitochondria wrap around proximal flagellum forming mitochondrial sheath
- characteristic of middle piece of sperm tail
- Distal flagellum surrounded by fibrous sheath to form principal piece
- Tip of flagellum lacks fibrous sheath ⇒ end piece
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Spermiogenesis
Maturation phase
The morphological differentiation of spermatids into spermatozoa.
Can be divided into four phases:
Stage 4: Maturation phase
-
Excess cytoplasm pinched off as residual bodies
- includes cytoplasmic bridges joining clonally related spermatids
- phagocytized by Sertoli cells
- Individual spermatozoa released into lumen of seminiferous tubule ⇒ spermiation
- Sperm are morphologically mature upon release but only become motile in the epididymis
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Spermatozoan Morphology
-
Head
- Elongated and highly heterochromatic nucleus
-
Acrosome
- Large flattened lysosome that covers anterior 2/3 of nucleus
-
Tail subdivded into 4 regions
-
Neck (connecting piece)
- modified centrioles
-
Middle piece
- Mitochondrial sheath
- 9 outer dense fibers
- Axoneme of flagellum (9+2 arrangement of microtubules)
-
Principal piece
- fibrous sheath replaces mitochondria
- 7 outer dense fibers
- Axoneme
-
End piece
- only contains axoneme
- loses characteristic 9+2 arrangement towards the end
- only contains axoneme
-
Neck (connecting piece)
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Cycles of Seminiferous Epithelium
- 6 stages characterize seminiferous epithelium during spermatogenic maturation
- Stages occur in a mosaic pattern without waves
- wave ⇒ distance along tubule length required to accomodate all stages
- Each stage has a specific grouping of spermatogenic cell types
- Cycle ⇒ time it takes a region to pass through all 6 stages ⇒ 16 days
- Complete differentiation of gamete from spermatogonium to mature spermatozoa takes 74 days.
- Passage through male reproductive tract to epidydymis takes 12 days.
- Takes a minimum of 86 days from dark type A spermatogonium to ejaculated sperm.
Testicular Interstitial Tissue
- Abundant fenestrated capillaries
- CT, lymphatics, and nerve fibers
- Leydig cells
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Leydig Cells
- Intersitial cells of the testes
- Produce testosterone
- appear during embryogenesis due to HCG stimluation
- regress until puberty
- resume testosterone synthesis at puberty in response to pituitary hormones specifically LH
- secrete into fenestrated capillaries
- enzymes involved in testosterone synthesis located in mitochondria and SER
-
Large rounded or polygonal cells
- pale foamy eosinophilic cytoplasm
- many small lipid droplets
- extensive SER
- contains enlongated proteinaceous crystals of Reinke
- unknown function
- Inactive cells resemble fibroblasts in prepubertal boys
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Hormonal Regulation
Male Reproduction
Activation
- LH from anterior pituitary stimulates testosterone synthesis by Leydig cells.
-
Testosterone stimulates sperm production:
- Indirectly by acting on Sertoli cells
- Directly by acting on spermatogenic cells
-
FSH from anterior pituitary stimulates Sertoli cells to synthesize androgen-binding protein
- Concentrates testosterone in seminiferous tubules at levels high enough to sustain spermatogenesis
Negative Feedback
- Testosterone inhibits release of LH from anterior pituitary
-
Sertoli cells secrete inhibin
- Inhibits FSH and LH secretion by anterior pituitary
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Male Reproductive Tract
Responsible for the production of semen.
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Semen
- Fluid consisting of spermatozoa and seminal fluid
- Mostly derived from seminal vesicles and prostate gland
- ~ 3 ml with 50-150 million sperm/ml
- 20% abnormal
- 25% immotile
-
Alkaline
- Helps neutralize acidic urethra and vagina
- Contains prostaglandins
- Aids in moving sperm through male and female reproductive tracts
Excurrent Duct System
Structure and Function
- Functions:
- Transportation of spermatozoa from test out of body
- Secretion by accessory glands
- Delivery of speramtozoa into female reproductive tract
- Components:
- Straight tubules (tubuli recti)
- Rete testis
- Ductuli efferentes (efferent ductules)
- Ductus epididymis
- Ductus deferens (vas deferens)
- Ejeculatory duct
- Urethra
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Straight Tubules
(Tubuli recti)
- Short, straight tubules
- Joins the seminiferous tubules with rete testis
- Found near the mediastinum at both ends of each U-shaped seminiferous tubule
- Epithelium:
- first part ⇒ only Sertoli cells
-
near termination ⇒ narrows and changes to simple cuboidal
- composed of non-Sertoli cells
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Rete Testis
- Series of very irregular channels
- Located within the mediastinum
- Receive sperm from tubuli recti
- Empty into efferent ductules
- Lined by simple low cuboidal to low columnar epithelium
- Apical surface:
- short microvilli
- single flagellum
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Efferent ductules
(Ductuli efferentes)
- 10-20 ducts connect rete testis with epididymis
-
Scalloped appearance of epithelium due to groups of alternating:
-
Tall ciliated columnar cells
- Only portion of tract with motile cilia
- Helps move sperm towards epididymis
-
Low nonciliated cells
- Absorb fluid produced in seminiferous tubules
- Contributes to drawing sperm out of testis
- Basal stem cells - few in number
-
Tall ciliated columnar cells
- Single layer of circular smooth muscle
- Coils into several conical masses ⇒ coni vasculosi
- Bases of coni vasculosi unite to form head of epididymis
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Ductus Epididymis
- One long tortuous tube with 3 parts: Head, Body, Tail
- Lined by pseudostratified columnar epithelium of uniform height
- Single layer of circular smooth muscle in head and body
- Gradually increases in thickness
- Inner and outer longitudinal layer with middle circular layer of smooth muscle in the tail
-
Principal cells:
- Have sterocilia (long non-motile microvilli) that reabsorb fluid
- First part of duct system that contains lymphocytes called halo cells
- Sperm mature and become motile here.
- Tail region acts as reservoir for sperm.
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Capacitation
- Initiated due to conditions found in female reproductive tract
- Includes development of hypermobility
- stronger whip-like flagellar motion
- required to penetrate the egg
- Ion channels in sperm plasma membrane involved
- Ex. Hv1 channel (transports H+)
- Results in the ability to fertilize an egg
Ductus Deferens
(Vas Deferens)
- Thick walled muscular tube
- Part of the spermatic cord
-
Pseudostratified columnar epithelium
- Shorter than epididymis
- Shorter stereocilia
- Muscularis consists of inner & outer longitudinal layer with middle circular layer of smooth muscle
-
Ends distally with the ampulla
- Lumen widens
- Pseudostratified columnar epithelium with folds
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Ejaculatory Duct
- Formed by the union of vas deferens with duct of the seminal vesicle
- Two ejaculatory ducts open into prostatic urethra at colliculus seminalis
- Pseudostratified to simple columnar epithelium
Prostatic Urethra
- passes through prostate gland
- upper region ⇒ transitional epithelium
- lower region ⇒ stratified or pseudostratified columnar
- receives two ejaculatory ducts and ducts of prostatic glands
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Membranous Urethra
- Part that passes through the urogenital diaphragm
- Stratified columnar epithelium
- Fibroelastic lamina propria
- Surrounded by the skeletal muscle of urogenital diaphragm which forms the external urethral sphincter
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Penile “Spongy” Urethra
- Portion that passes through the corpus spongiosum
- Lined with pseudostratified columnar epithelium
- Except at distal end near external orifice ⇒ becomes stratified squamous epithelium
- Patches of both as well as stratified columnar often found side by side
- Receive ducts from:
- Bulbourethral glands
- Glands of Littré
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Spermatic Cord
- Includes:
- Vas deferens
- Testicular artery
- Pampiniform plexus of veins
- Cremaster muscle
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Seminal Vesicles
Structure & Development
- Paired glands
- Duct of each gland unites with vas deferens to form ejaculatory duct
- Single, highly coiled, wide-bore tube
- Lined with pseudostratified columnar epithelium
- Mucosal folds form saclike invaginations and arcades
- Creates distinctive “honeycomb” appearance of lumen
- Inner circular and outer longitudinal smooth muscle
- Mesonephric (Wolffian) duct gives rise to vas deferens & seminal vesicles are outgrowths of the vas.
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Seminal Vesicles
Functions
- Contributes over half the volume of semen
- Viscous whitish yellow product
-
Secretions include:
- fructose ⇒ main metabolic substrate for sperm
- ascorbic acid
- flavins ⇒ fluorescent yellow pigments used in foresics for semen detection, gives sperm its pale color
- semenogelins ⇒ proteins involved in semen coagulation, substrate for PSA
- prostaglandins
- Activity controlled by testosterone.
Prostate
Structure & Development
- Derived from the urogenital sinus
-
Musculo-glandular organ
- Large amount of fibro-muscular stroma
- smooth muscle and CT mixture
- Epithelial glandular elements
- 30-50 tubuloalveolar glands
- Large amount of fibro-muscular stroma
- Surrounds the prostatic urethra
- Divided into multiple regions
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Prostate Regions
-
Periurethral zone
- immediately around the urethra
-
Transitional zone
- surrounds periurethral layer and extends anteriorly
-
Central zone
- posterior to transitional zone
- includes the ejaculatory ducts
-
Peripheral zone
- surrounds distal part of periurethral zone
- extends to capsule posteriorly and laterally
- comprises the bulk of the organ
- contains majority of prostatic glandular tissue
- site of carcinomas
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Prostate Glands
- Contains 30-50 tubuloalveolar glands
- Lined by pseudostratified columnar epithelium
- Contains sparse flat basal cells
- Contains concretions
- calcified precipitated secretions
- have concentric layers
- seen in older men
-
Glands subdivided based on size and location:
-
Mucosal glands
- small glands
- immediately surrounds urethra in periurethral zone
- seperated from remainder of prostate by smooth muscle
- each empties seperately into the prostatic urethra
-
“True” prostatic glands (Prostate glands proper)
- larger and highly branched
- subdivided into:
-
Submucosal glands
- transitional zone and a little in central zone
-
Main prostatic glands
- peripheral zone
- palpated via digital rectal exams
-
Submucosal glands
-
Mucosal glands
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Prostate Secretions
- Colorless and less viscous secretion
- Makes up 30-50% of seminal fluid volume
- Contains:
- citric acid
- acid phosphatase
-
proteolytic enzymes ⇒ liquefaction of semen
- fibrinolysin
- prostate-specific antigen (PSA)
- Activity maintained by dihydrotestosterone (DHT)
Benign Prostatic Hypertrophy
(BPH)
- nodular hyperplasia
- fibromuscular stroma
- mucosal or submucosal glands
- leads to urethral constriction
- most frequent near urethra rather than in peripheral zone
- usually treat with Finasteride
- inhibits 5-𝛼-reductase: testosterone → DHT
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Prostatic Adenocarcinoma
- Originates from glandular epithelium
- Can be found anywhere but mostly in peripheral zone
- Usually involves simple epithelium
- Diagnostic tests:
- PSA in blood
- Other organs also release
- Released with other conditions
- Digital rectal exam
- Transrectal ultrasound
- PSA in blood
Bulbourethral glands
(Cowper’s glands)
- Structure:
- tubulo-alveolar glands
- mucous secreting
- located in the skeletal muscle of urogenital diaphragm
- ducts empty into penile urethra
- dependent on DHT
- height of cells varies directly with levels
- Secretion:
- activated by erotic stimulation
- major portion of pre-seminal fluid ejaculate
- secretes alkaline mix of glycoproteins
-
neutralizes acidity of:
- urine in urethra
- vagina
- helps lubricate urethra
-
neutralizes acidity of:
- small nutrient molecules
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Penis
- Includes 3 erectile bodies
- Paired corpora cavernosa
- Dorsally located in erect penis
- Single corpus spongiosum
- Ventrally located in erect penis
-
Urethral glands of Littré found here
- open into penile urethra
- produces mucus to protect urethra
- Paired corpora cavernosa
-
Tunica albuginea surrounds each erectile body
- dense irregular CT
- thicker in corpora cavernosa
- fused to form incomplete midline septum
- Composed of erectile tissue containing:
-
Caverous spaces ⇒ thin-walled irregularly shaped veins
- Supplied by helicine arteries located in CT septa
- CT trabeculae ⇒ seperates spaces
-
Caverous spaces ⇒ thin-walled irregularly shaped veins
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Erection
- Helicine arteries contracted at baseline
- Minimal blood entering erectile tissue
- Sexual arousal ⇒ PNS stimulation ⇒ relaxation of muscle in helicine walls
- Increased blood flow into cavernous spaces of erectile tissue ⇒ erection
- Filling compresses efferent veins against tunica albuginea ⇒ contributes to engorgement
- Thinner tunica albuginea in corpus spongiosum prevents efferent vein compression ⇒ lower pressure ⇒ patent urethra for ejaculation
Ejaculation
Occurs in two stages:
-
Emission
-
Smooth muscle contraction in ductus deferens and seminal vesicles
- Under sympathetic control
- Delivers spermatozoa from epididymis ⇒ base of penile urethra
-
Smooth muscle contraction in ductus deferens and seminal vesicles
-
Ejaculation
-
Reflex contraction of bulbospongiosus muscle
- Skeletal muscle
- Under somatic motor neuron control
- Sensitized by sympathetic input during orgasm
- Contraction ejects semen out penile urethra
-
Reflex contraction of bulbospongiosus muscle
Detumescence
- Ejaculation followed by cessation of parasympathetic stimulation to vascular supply of penis
-
Re-contraction of helicine arteries after orgasm
- Reduces blood flow into erectile bodies
- Decompresses efferent veins
- Allows blood to drain
- Blood leaves vascular spaces ⇒ penis becomes flaccid