UROGENTIAL

Question 1

Structure of the kidney, nephron

Answer 1

General:

• Urinary system: kidney, ureter, urinary bladder, urethra
• The kidneys are large, paired bean-shaped organs located retroperitoneally on either side of the vertebral column
  
  • Funtion:
    
    • Excretion of waste products,
    • Regulation of extracellular fluid volume and osmolality,
    • Maintenance of acid-base balance,
    • Functions as an endocrine organ
      
      • Synthesis of erythropoietin EPO
        
        • Acts in bone marrow and regulates RBC formation
      • Synthesis renin
        
        • involved in BP and BV, produced in jutaglomerular cells
      • Hydroxylation of vitamin D
        
        • Hydroxylation of the precursor
          of the vitamin D3 produced by liver
          into active form (1,25 dihydroxycholecalciferol)

Structure overview

Renal capsule

• Outer fibroblast and collagen layer, dense irregular CT
• Inner cellular component of myofibroblasts
• Renal capsule lies directly on the surface of the renal cortex
  
  • Also contains the adrenal glands
• Contains nociceptors → renal inflammation and/or urinary outflow obstruction cause swelling of the kidney → strain on the renal fascia → pain

​Renal cortex

• Outermost layer of the renal parenchyma
  
  • Surface cortex: 5-10 mm surface layer
  • Renal columbs: ​Cortex columns extend into the medulla
    
    • Running between medullary pyramids
• Contains glomeruli, proximal convoluted tubules, distal convoluted tubules, and renal vessels

Renal medulla

• Consists of 7–12 medullary pyramids
  
  • Medulary rays
    
    • Straight portions of PT, DT, CT
    • Between each ray: convoluted tubules of nephron, collecting tubules=
      
      • Cortical Labyrinth (PT, DT)
• Renal papillae: apices pf pyramids
• Renal lobuli: fromed by medullary rays and adjacent cortex
• Renal lobi: fomred by initial pyramis and ajacent cortex
• Contains loop of Henle and collecting ducts

Renal pelvis

• Connects to the ureter
• Minor calyces
• Major calyces
• Ureteropelvic junction

Nephron: Functional unit of each kidney

• Urine production
• Subdivided into two components:
  
  • Renal corpuscle
  • Renal tubules
• There are two types of nephrons.
  
  • Cortical nephrons:
    
    • Located in the cortex of kidney
  • Juxtamedullary nephrons:
    
    • Situated near the junction of the cortex and medulla of the kidney.

Renal corpuscle

• Glomerulus: tuft of capillaries
• Bowman’s capsule: double layer of epithelial cells
• The renal corpuscle is the initial segment of each nephron.
• General:
  
  • Blood is filtered in renal corpuscles through the capillaries of the glomerulus, and the filtrate enters the capsular (urinary) space located between the parietal and visceral cell layers of the glomerular capsule.

Glomerulus:

• Capilary loops
  
  • Fenestrated (without diaphragm)
    
    • Endothelial cells contain pores
    • Pore= true opening which is not covered or supported by anything
    • Continous basal lamina
    • Only present in glomeruli
• Blood flowing undergoes filtration to produce glomerlar ultrafiltrate
  
  • Afferent arterole→ effernet arteriole
• Mesangial cells
  
  • Attached to the capillaries
  • Function
    
    • Synthesize the extracellular matrix
    • Provide structural support for the glomerular capillaries.
    • Function as macrophages in the intraglomerular regions
      
      • Phagocytose material that accumulates on the glomerular filter, thus preventing its clogging with debris.
    • Appear to be contractile
      
      • Can regulate glomerular blood flow
• Extraglomerular mesangial cells
  
  • Located outside of the renal corpuscle in the vascular pole region.

Bowman’s capsule:

• Double layer of epithelial cells
  
  • Inner or visceral layer of the capsule
    
    • Podocytes: highly modified branching epithelial cells
      
      • Larger primary process
        
        • Extends from the podocyte cytoplasm
        • Surround the wall of the capillary.
      • The smaller pedicles
        
        • Attached to the basement membrane of the capillary
        • Between the individual pedicles are the filtration slits
  • The outer or parietal layer
    
    • Consists of simple squamous epithelium
• Poles
  
  • Vascular pole
    
    • Entry site of capillaries
      
      • Where the afferent arteriole enters and the efferent arteriole leaves the corpuscle.
  • Urinary pole
    
    • On the opposite end of the renal corpuscle
      
      • Where the proximal convoluted tubule starts.
    • Filtrate produced by the glomerulus that enters the capsular space leaves each renal corpuscle at the urinary pole

Glomerular filtration barrier and juxtaglomerular complex:

1- Glomerular filtration barrier

• A membrane consisting of 3 layers that allows selective filtration of blood plasma components based on their size and charge
• Fenestrated glomerular capillary endothelium
  
  • Fenestrations=70nm pores
    
    • Large aquaporin water channels
    • No diaphragm
• Glomerular basement membrane
  
  • Basal lamina that is a joint product of endothelium and podicytes (cells of the viseral layer of bowmans capsule)
  • 300 nm thick
    
    • Principal component of the filtration barrier
  • Acts as a physical barrier and an ion-selective filter
    
    • Polyanionic GAGs restrict movement of cationic particles
• Podocytes: viseral layer of bowmans capsule
  
  • ​Foot processes that surround the capillaries and leave filtration slits (slit diaphragms)
  • 30 nm, elongated spaces between interdigitating foot processes, filtration slit membrane
  • In contact with the endothelium of glomerular capillaries

2- Juxtaglomerular complex

• Specialized structure that is located between the distal convoluted tubule and the afferent arteriole of the nephron
• Regulates BP by activation renin angiotensine- aldosterone sytem
• Parts
  
  • Extramesangial cells (explained above)
  • Juxtaglomerular cells:
    
    • Modified smooth muscle cells located in the afferent arterioles
    • Function: secratory, synthesis of renin
  • Macula densa:
    
    • Dark area
    • Tall cuboid cells in the distal convoluted tubule, ncl have crowded appearnce
    • Monitors the NaCl concentration within the lumen of the DCT
      
      • Hypoosmolar urine triggers the release of renin → vasoconstriction of the efferent arteriole → increase in GFR
      • Hyperosmolar urine triggers the release of adenosine → vasoconstriction of the afferent arteriole → decrease in GFR

Renal tubules

Proximal convoluted tubule

• Parts:
  
  • Long convoluted part, located entirely in the cortex,
  • Shorter straight part that enters the medulla;
• Structure:
  
  • Nuclei not always present on section
  • Eosinophilic cytoplasm
  • Tall epithelial cells with brush border (long apical microvilli)
    
    • Alkaline phosphatase (azocoupling method)
  • Basal invaginations/striations with multiple mitochondria
    
    • heidenhain ́s method
• Function:
  
  • Absorptive epithelium, ion transport
  • Reabsorb the glucose, amino acids, ascorbic acids, chloride, and sodium from the filtrate within the tubule.

Loops of Henle: intermediate part

• Nephron loop: renal medulla
• Thin descending loop of Henle
  
  • Smaller diameter than PCT
  • Flat epithelium (resembles capillary endothelium)
• Thick ascending loop of Henle
  
  • Wider diameter than the descending segment
  • Epithelium with variable short brush border and tight junctions (impermeable to water)
• Distal tubule
  
  • Directly adjacent to the nephron’s glomerulus
  • Thick straight part ascending from the loop of Henle back into the cortex
  • Convoluted part completely in the cortex
  • Characteristics:
    
    • Regular lumen,
    • Simple cuboidal epithelium
      
      • Cells are smaller, and more nuclei are seen per tubule
    • Less eosinophilic cytoplasm
      
      • No brush border
    • Basal striation is developed
  • Function
    
    • Distal convoluted tubules
    • Actively reabsorb sodium ions from the tubular filtrate.
    • This activity is directly linked with excretion of hydrogen and potassium ions into the tubular fluid.

Connecting tubule and collecting duct

• Tubule: simple buboidal to columnar
• Duct: starts in medullary ray, widens and merges to papillary duct

Papillary duct:

• Simple columnar, opening into small calyx

Types:

• subcapsular/cortical nephrons
  
  • renal corpuscles in outer part of cortex
  • short loop of henle
• juxtamedullary nephrons
  
  • long loop of henle
• intermediate nephrons

Question 2

Relationship of nephron and vascular supply of the kidney

​

• Leave the renal corpuscles and form:
  
  • 1- Complex peritubular capillary network
    
    • Around the tubules in the cortex
  • 2- Long, straight capillary vessels or vasa recta
    
    • ​In the medulla
    • Loops back to the corticomedullary region.
    • Vasa recta forms loops that are parallel to the loops of Henle.
• The interstitium is drained by interlobular veins that continue toward the arcuate veins.

Answer 2

General:

• Kidneys
  
  • Large, paired bean-shaped organs located retroperitoneally on either side of the vertebral column
  • A part of the urinary system
• Funtion:
  
  • Excretion of waste products,
  • Regulation of extracellular fluid volume and osmolality,
  • Maintenance of acid-base balance,
  • Functions as an endocrine organ
    
    • Synthesis of erythropoietin EPO
      
      • Acts in bone marrow and regulates RBC formation
    • Synthesis renin
    • involved in BP and BV, produced in jutaglomerular cells
    • Hydroxylation of vitamin D

Structure:

• Contains: capsule, cortex, medulla and a renal pelvis→ ureters
• Nephron: Functional unit of each kidney
  
  • Urine production
  • Subdivided into two components:
    
    • Renal corpuscle
    • Renal tubules

To understand the functional correlation of the kidney, it becomes important to understand the blood supply of the organ.

• Each kidney is supplied→
• Renal artery:
  
  • Divides in the hilus into several segmental branches→
  • Which branch into several interlobar arteries.
• Interlobar arteries→ continue inbetween the pyramids toward the cortex.
  
  • At the corticomedullary junction the interlobar arteries branch→
• Arcuate arteries
  
  • Which arch over the base of the pyramids and give rise to→
• Interlobular arteries→
• Afferent arterioles→
  
  • Which give rise to the capillaries in the glomeruli of renal corpuscles.
• Efferent arterioles→
• (gives rise to…)
  
  • From glomeroli in outer cortex: to peritubular capillaries
    
    • ​satalite viens
    • interlobular viens (cortical radiate)
  • From glomeroli in near medulla (juxtamedullary glomeruli): to rectae arterioles to medullary pritubular plexsus
    
    • ​straight velnules
• →​Arcuate vien
• →Interlobular vien
• →Segmental vien
• →R/L renal vien

EXTRA:

• Renal capsule
  
  • Outer fibroblast and collagen layer, dense irregular CT
  • Inner cellular component of myofibroblasts
  • Renal capsule lies directly on the surface of the renal cortex
  • Also contains the adrenal glands
    
    • Contains nociceptors → renal inflammation and/or urinary outflow obstruction cause swelling of the kidney → strain on the renal fascia → pain
• ​Renal cortex
  
  • Outermost layer of the renal parenchyma
  • Surface cortex: 5-10 mm surface layer
  • Renal columbs: ​Cortex columns extend into the medulla
  • Running between medullary pyramids
  • Contains glomeruli, proximal convoluted tubules, distal convoluted tubules, and renal vessels
• Renal medulla
  
  • Consists of 7–12 medullary pyramids Medulary rays
  • Straight portions of PT, DT, CT
  • Between each ray: convoluted tubules of nephron, collecting tubules=
    
    • Cortical Labyrinth (PT, DT)
  • Renal papillae: apices pf pyramids
  • Renal lobuli: fromed by medullary rays and adjacent cortex
  • Renal lobi: fomred by initial pyramis and ajacent cortex
  • Contains loop of Henle and collecting ducts
• Renal pelvis
  
  • Connects to the ureter
  • Minor calyces
  • Major calyces
  • Ureteropelvic junction

Nephron: Functional unit of each kidney

Urine production

Subdivided into two components:

Renal corpuscle

Renal tubules

There are two types of nephrons.Cortical nephrons:

Located in the cortex of kidney

Juxtamedullary nephrons:

Situated near the junction of the cortex and medulla of the kidney.

Question 3

Excretory urinary passages

Answer 3

The urinary system

• Composed of the
  
  • Kidneys, ureters, urinary bladder, and the urethra.
• Function:
  
  • Maintain the fluid balance of the body
  • Filter toxic substances from the bloodstream.
• Pathway:
  
  • Urine is generated by the kidneys
  • Carried to the bladder through the ureters.
  • From the bladder, it is released through the urethra.

Glomeruli (renal cortex) → Bowman capsule and space → proximal convoluted tubule (PCT) → loop of Henle → distal convoluted tubule (DCT) → collecting ducts → drain into the minor calyces → major calyces → renal pelvis → ureter → bladder → urethra

All excertory passages except urethra have the same general organization

1- Mucosa

• Transitional epithelium= urothelium
  
  • Pseudostratified, adaptive
  • Impermiable to salts and water
  • Cells:
    
    • Basal cells: stem
    • Columnar cells
    • Umbrella cells
      
      • Protect against cytotoxic affect of urine
      • Shape and structure:
        
        • Polyhedral cells
        • Modified plasma membrane:
          
          • Plaque (uroplakin (I-III), apical plasma membrane
            
            • In phospholipid layer
            • The plaques are connected to thinner, shorter, and more flexible interplaque regions.
            • These structures act like “hinges,” the interplaque regions allow the cell membrane to fold.
            • The plaques are impermeable to water, salts, and urine,
            • Fusiform vesicles:
              
              • Develop during contraction of cells
              • Invagination of apical membrane
          • MF, IF: connect to plaque, prevent over extention
• Lamina P: dense collagenous layer
• No muscularis mucosae, and submucosal layer
• Tunica muscularis:
  
  • Inner longitudinal layer: loose spiral pattern
  • Outer circular layer: tight spiral pattern
    
    • This is opposite of intesinal tract
  • Smooth muscle here is mixed with CT, forming prarallel bundles rather that pure sheets
• Tunica adventita
  
  • ​except in bladder

Ureter

• Conduct urine from renal pelvis to bladder
• Transitional epithelium
• Muscular layers: contract and relax in a peristaltic pattern
  
  • Inner longitudinal layer
  • Outer circular layer
  • Outer longitudinal layer (mainly present in the distal third of the ureter)
  • Muscular layer is not continuous with that of the urinary bladder
• ​Adventitia

Urinary bladder

• Resuvoir for urine
• Transitional epithelium
• Muscular layers
  
  • Inner longitudinal layer: plexiform layer
  • Middle circular layer: sphincter vesicae
  • Outer longitudinal layer
• 3 openings
  
  • Triangular region deffined by openings: trigone
    
    • Smooth with constant thickness
• Adventita- majority
• serosa
  
  • F: majority of upper surface
  • M: whole upper/post surface

Urethra FUCK BLAH GO OVER THE DIFFRENCES

In males

• Urothelium
  
  • prostatic part
  • ​intramural part
• Stratified columnar epithelium
  
  • intermediate part
  • spongy part
• Stratified squamous non k
  
  • navicular fossa (inside glans penis)
• Stratified squamous k
  
  • on transition of external urethral osteum and glans of penis
• Morgagni Glands:
  
  • in spongy urthra
  • intrapithlia glands from mucinous cells

​

• Lamina P
  
  • littres glands
    
    • exorine mucinous
    • branched tubular
• Tunica muscularis
  
  • inner longitudinal
  • outer circular
    
    • wider in intramural part: intrmural sphincter
  • intermedial part: also outer layer of skeletal muscle (ex urethral sphincter
• Tunica adventita
• Transitional epithelium in the prostatic urethra
• Stratified columnar epithelium in the membranous and spongy urethra
• Muscular layers
  
  • Prostatic: inner longitudinal and outer circular layers
  • Membranous: skeletal muscle fibers from the urogenital diaphragm make up the external urethral sphincter
  • Spongy: sparse smooth muscle with more elastic fibers
• In females
  
  • Stratified squamous epithelium
  • Some stratified columnar epithelium can also be present
  • Muscular layers
    
    • Inner longitudinal layer
    • Outer circular layer
    • Skeletal muscle fibers from the urogenital diaphragm make up the external urethral sphincter

Female:

Male:

• Mucosa
  
  • Urothelium
    
    • ​intramural part
    • prostatic part
  • Stratified columnar epithelium
    
    • intermediate part
    • spongy part
  • Stratified squamous non k
    
    • navicular fossa (inside glans penis)
  • Stratified squamous k
    
    • on transition of external urethral osteum and glans of penis
  • Morgagni Glands:
    
    • in spongy urthra
    • intrapithlia glands from mucinous cells
• Lamina P
  
  • littres glands
    
    • exorine mucinous
    • branched tubular
• Tunica muscularis
  
  • inner longitudinal
  • outer circular
    
    • wider in intramural part: intrmural sphincter
  • intermedial part: also outer layer of skeletal muscle (ex urethral sphincter
• Tunica adventita

Female

• Tunica mucosa
  
  • Low longitudinal folds on posterior wall
  • Urothelium
    
    • intramural part
  • Stratified squamous non K
    
    • pelvic and perineal part
  • Morgagni Glands:
    
    • intrapithlia glands from mucinous cellsm in epithlium
  • Lamina P
    
    • loose CT
    • Skene glands
      
      • exorine mucinous
      • branched tubular
    • Spongy layer
      
      • strong venous plexsus helping hold urine
• Muscular layer
  
  • Inner longitudinal
  • In perineal part also external layer of skeletal muscle: ex urethral sphincter, comprssor urthrea m. urethrovaginalis m)
• Tunica adventita

Question 4

Testis, spermatogenesis

Add blood testies barier

Answer 4

Male reproductive system

• Structure:
  
  • Testes
  • Genital ducts
  • Accesorry sex glands: seminal cesicles, prostate, bulbourethral gland
  • Penis
• Function:
  
  • Spermatogenesis
  • Steroidogenesis (Production of androgens- sex hormones)

Spermatogenesis= Process by chich spermatogonia develop into sperm

• Duration 74 days

1- Spermatogonial phase

• Spermatogonial stem cells divide by mitosis to to provide a population of spermatogonia
• Classification of cells:
  
  • A dark
    
    • ovoid ncl, inensly basophillic
    • fine granular chromatin
    • stem cells of seminiferous spithelium
  • A pale
    
    • ovoid ncl, pale stained
    • fine granular chromatin
    • produce sperm
  • B
    
    • Spherical ncl, largly clumps of condensed chromatin alaong ncl envelope round central nucleolus
  • A diffenciates into B?

2- Spermatocyte phase (meiosis)

• General: primary spermatocyte undergoes meiosis to reduce the chromosome number and amount of DNA
• Mitotic division of B cells produces primary spermatocytes
• Before meiosis, 2n chromosomes and 4d DNA
  
  • Meiosis I: product- secondary spermatocyte: results in reduction to 1n and 2d (haploid)
    
    • Prophase I:
      
      • leptotene, zygotene, pachytene, diplotene and diakinesis
      • Lasts for 3 weeks
      • chromatin condenses into visable chromosomes
    • Metaphase I, anaphase I, telophase I, incomplete cytokinesis
      
      • Paired homologus chromosomes align (tetrads), and crossing over (in synaptonemal complexes), seperate
  • Meiosis II: product- spermatid: 1n, 1d (hapoloid)
    
    • Secondary spermatocytes enter prophase II w/o synthesysisng new DNA
    • Metaphase: sister chromatids line up
    • A: seperate

3- Spermatid phase (spermiogenesis)

• Extensive cell remodeling and diffrentiation into mature sperm
• spermatind 1n, 1d
• Golgi phase
  • Acrosomal vesicles-granules rich in glycoproteins and mitochondria shifted to the periphery
    
    • Determining anterior pole of sperm
  • Centrioles migrate to the opposite pole of the nucleus (posterior pole), distal centriole starts to form the axoneme
    
    • initiated the assembly of 9 peripheral microtubule doublets and 2 central microtubules the consitiue the axoneme of the sperm tail
• Cap phase
  
  • Acrosomal vesicle extends and stretches over the anterior part of the nucleus
• Acrosomal phase
  
  • Spermatid is turning and is deeply inserted into the Sertoli cell cytoplasm.
  • Development of the the tail, condensation and elongation of the nucleus.
    
    • Developing flagellum extends into the lumen of the seminiferous tubule
  • Microtubule manchette
    
    • Organisation of cytoplamsic mictotubules into a cylidrical sheath which extends from the posterior rim of the acrosome twards the posterior pole
  • Cytoplasm is pulled back
  • Mitochondria form a sheath in the middle piece.
• Maturation phase–> mature spermatozoon
  
  • Advancing chromatin condensation
  • Phagocytosis of exsess cytoplasm by Sertoli cells (AKA residual body)
  • Release of spermatozoa into the lumen of the seminiferous tubule (AKA: spermination)
  • Disconnections of intercellular bridges.

Newly released sperm cells are processed in the epididymis where they aquire motility and undergo further maturation

• Carried by fluid secreted from the sertoli cells
• Though the seminiferous tubules, facillitated by peristaltic contractions
  
  • of peritubular contractile cells of the lamina proptia
• Enter straight tubules
• At mediastinum the fluid and sperm enter the rete testies: simple cuboidal epithelium
• Move into the extracellular portion of the efferent ductules
  
  • first part of the excurrent duct system
• And then to the proximal protion of the duct of epididymis
• As they move through the highly colied duct they aquire motility and undergo several maturation stages
  
  • Condensation of DNA, head of sperm decreases in size
  • Further reduction of cytoplasm- cells becomes more slender
  • Changes in plasma membrane lipids, protiens and glycosylation
  • Alteration in the outer acrosomal membrane (decapitation)
• duct of epididymis

Mature sperm:

• Head -
  
  • the mass of the largest part of sperm, contains a nucleus with haploid genetic equipment (n) and cytoplasm.
  • In front of the head is a sac called an acrosome , which was formed during spermatogenesis by fusing the follicles of the Golgi apparatus .
    
    • It acts as a lysosome and serves to disrupt the structures surrounding the oocyte (corona radiata and zona pellucida).
    • It contains several hydrolytic enzymes such as hyaluronidase (it breaks down glycosaminoglycans), acrosin (protease), neuraminidase and acid phosphatase .
• Neck - a structure connecting the head and the whip.
• Tail - the part of the sperm that allows it to move. It contains a bundle of microtubules anchored in the basal body. It consists of three segments:
  
  • Connecting (middle) segment - contains a number of mitochondria providing energy for movement.
  • Main segment .
  • End part .

The size of the sperm is about 60 μm, of which only 5 μm falls on the head, the rest is the flagellum.

Testis

General:

• Paired ovoid organ in scrotum
• Connected by spermatic cord to abdominal wall and to the srotum by scrotal ligaments

Development:

• Develop on posterior wall of abdomen and later desend into scrotum
• Derived from three sources:
  
  • Intermediate mesoderm
    
    • Forms urogential ridge on posterior abdomional wall
    • Giving rise to
      
      • Leydig cells (interstitial cells)
      • Myoid cells (peritubular contractile cells)
  • Mesodermal epithelium
    
    • Lines urogential ridge and gives rise to sertoli cells
  • Primordial germ cells
    
    • Migrate from yold sac intp developing gonads, where they divide and diffreincate into spermatogonia
    • this migration induces mesodermal cells to form primary sex cords- into seminiferous cords

Structure:

1-Tunica vaginalis

• Double serous membrane forming a sac around the testis
• Contains collageous CT and in its inner surface its lined with mesothelium
  
  • Lamina viseralis: epiorchium (inner)
  • Cavitas vaginalis tesits
  • Lamina parietialis: periochium (outer)
• Inner part of capsule:
  
  • loose CT layer containing blood vessels

2-Tuncica albuginea

• Dense CT capsule
• Covers testis
• Thickened on the dorsal side and forms the mediastinum testis
  
  • Rectus testis:
    
    • network of exceratory ducts forming the the mediastinum
    • Slit-like spaces in the mediastinum testis
    • Lined with simple squamous to columnar epithelium
    • Fibroblasts, myofibroblasts, wide lymphatic vessels, clusters of Leydig cells around blood vessels
    • columnar sertoli cells marks the transition form seminferous epithelium to tubules rectus
    • basal tight junctions change into apical tight junctions between cuboidal sertoli cells at tubulus rectus and rete tesis
      
      • apical domaine displays microvilli and occasional cillium
  • Tubuli recti (straight tubules):
    
    • tubules in the mediastinum testis, simple cuboidal epithelium, cells are similar to Sertoli cells
• It sends inside the testis CT septa which divides it into the lobula testis.
  
  • 250-350 lobules in each testis

3-Convuluted seminiferous tubules:

• In each of the lobules there are 1 - 4 tubules
• Ø of the tubules 150-250 μm
• Lined with the germinal epithelium
• Surrounded by the connective tissue layer (tunica propria):
  
  • Collagen fibers, fibroblasts and myofibroblasts (myoid cells)
• Sperm produced in these tubes
• End of the conulated loop is near mediastinum, where thye assume a short striaght course
• Cells:
• Sertoli cells: supporting cells
  
  • The dominant cell type in the tubules in childhood
  • From puberty cca 10% of cells
  • Proliferate until puberty, after that they become postmitotic
  • Columnar cells with extensive apical and lateal processes that surround adjacent spermatogenic cells and occupy the spaces between them
  • Functions of Sertoli cells:
    
    • They form a blood-testis barrier
    • Support, protect and nourish developing spermatozoa
    • Phagocytosis
    • Release of mature spermatozoa
    • Production of testicular fluid
    • Secretion of signaling molecules: activin, inhibin, anti-müllerian hormone (AMH)
    • Production of androgen-binding protein
• Spermatogenic cells
  
  • Regularly replicate and diffriciate into mature sperm cells
  • Derived from the primordial germ cells originating in the yolk sac that colonize in the gonadal ridges during early development of tesitis
  • Organized in poorly defined layers of progressive development between adjacent sertoli cells
    
    • most immature: spermatogonia- on basal lamina
    • most mature: spermatid: attached to apical portion

4- Tunica lamina propria

• AKA: peritubular tissue
• Mutlilayer CT, lacks typical fibroblasts
• 3-5 layers of myoid cells (peritubular contractile cells)
  
  • contain basal lamina
  • large number of actin fillaments
  • latge amount of RER: collagen sysntheis
• collagen fibrils
• Leydig cells:
  
  • interstitial cells
  • large, polygonal, eosinophillic cells
  • typicly contain
    
    • lipid droplets
    • lipofusin pigments- in rod shape cytoplasmic crytals, crystals of reinke
  • Steriod secreting cells
  • Elaborite SER (unlike other steriod secreting cells)
    
    • characteristic of sysnthesis of testosterone from cholesterol
  • Mitochondira with tubulovesicular cristae
  • Function
    
    • secrete testosterone during early fetal life, required for embryonic development, sextual maturation
    • undergo period of inactivity at 5 months of fetal life
    • when exposed to gonadotripic stimulation at puperty they become active

Question 5

Epididymis and vas deferens, structure and function

Answer 5

Epididymis

• Organ containing:
  
  • The efferent ductules
  • And the duct of epididymis
  • assosiated vessles smooth muscle and CT coverings
• Cresent shape strucutre around the superior and posterior side of testis
• Newly matured sperm which enter the spidydimis from the testis mature during passage through the duct
  
  • androgen- devendent process
  • head of sperm is modified by addition of assicuated decapacitation factor (occurs in female reproductive tract before fertaliztion)

Ductulus efferens

• Simple epithelium cuboidal and columnar cells – with microvilli or kinocilia
• Irregular profile, „star-shaped“ lumen
• Lamina propria mucosae: loose connective tissue + circular arrangement of myofibroblasts

Duct of epididymis

• Head - ductuli efferentes,
• 10-20 tubules body
• Tails – ductus epididymidis
• 4 – 6 m long tubule
• Pseudostratified epithelium
  
  • Principle cells:
    
    • Columnar cells with stereocilia
    • Vary in height
  • Basal cells
    
    • Small round cells in basal lamina
  • Intraepithelial lymphocytes, halo cells
• Thin layer of loose connective tissue
• Smooth muscle coat
  
  • Inner circular
  • Inner and outer longitudinal layer of smooth muscle (mainly towards the tail)
• Function:
  
  • Absorbtion
    
    • most of fluid that is not absrobed by effernet ductules it abbsorbed by the proximal part of epididymis
    • phanocytos any left residual bodies
  • Secretion
    
    • substances which aid in maturation of sperm

At the epididymis we can observe special formations:

• Appendix epididymidis = remnant of Wolff’s derivation
• Paradidymis = the rest of the mesonephrosal ductsin the area of ​​the epididymis head
• Ductuli aberrantes = remains of mesonephros in the area of ​​the body and tail of this organ

*The epididymis is supplied with blood from the artery separating from the testicular artery . The blood is then drained into the venous plexinus pampiniformis .

Duct deferens

• Direct continuation of tail of epididymis
• Assends along the posterior border of the testis
• Enters abdomen as apart of the spermatic cord, by passing through the inguinal canal
• Compostion of the wall:
  
  • Mucosa – folds, pseudostratified epithelia, stereocilia
  • Muscle layer – smooth muscle tissue
    
    • Consists of 2 or 3 layers
    • Deeper circular
    • Superficial longitudinal arrangements of muscle fibers.
    • There is also a third longitudinal layer in the proximal part.
  • Adventitia – loose connective tissue
• Ampula ductus deferentis – dilated portion, cuboidal to columnar epithelium
• Ductus ejaculatorius – opens at colliculus seminalis

Question 6

Accessory glands of the male reproductive system

ADD PENIS?

Answer 6

Seminal vesicles

• Two 15 cm long twisted tubes.
• Located lateral to the vas deferens, on posterior wall of urinary bladder
• a short exceretory duct from each semial vesicle combineds with the ampulla of the ductus deferens to form ejaculatory duct.
• Develop as invagination of mesonephric wolffian duct
• Their wall has three layers:
  
  • Mucosa
    
    • primary, secondary and teritary folds
    • pseuostratified columnar epithlium (non cilliated)
    • It has features characteristic of protein-secreting cells.
  • Thin layer of smooth muscle
  • Fibrous coat
• Secretion
  
  • Whiteish, yellowish color
  • Makes up almost seventy percent of the ejaculate
  • Carbohydrates (mostly fructose ), which supply sperm with energy for movement, and other simple sugars
  • Furthermore, there is a significant proportion of proteins for sperm activation .
  • The secretion of the bladder glands is dependent on testosterone .

Prostate

• Largest sex accsesory gland
• It is a chestnut-sized gland located in the pelvis between the urethra and the bladder.
• Main function: to secrete clear, slightly alkaline seminal fluid
  
  • Forms around 30% of ejaculate
  • Prostatic acid phosphatase PAP: regulates cell growgh and metabolism or glandular epithelium
  • Prostate-specific antigen PSA: tumor marker
  • Fibrinolysin: secreted from prostate gland, liquifies semen
  • amylase, citric acid, prostaglandins
• 30-50 branched tuboalveolar glands, arranged in 3 concentric layers:
  
  • mucosal layers
  • intermidiate submucosal layer
  • peripheral layer: contianing the main prostatic glands
• Adult prostatic parencyma zones:
  
  • Central zone 25%
    
    • Surrounds the ejaculatory ducts as they enter the prostate gland
    • Cells have a distinct morphologic feature: more prominent and slightly basophillic cytoplasm
  • Peripheral zone 70%
    
    • glandular tissue
    • area most susceptible to innflamation
  • Transitional zone 5%
    
    • Surrounds prostetic urethra
    • Contain mucosal glands
  • Perinrethral zone
    
    • Contain mucosal and submucosal glands

Bulbourethral glands (Cowper‘s)

• secrete periseminal fluid
• Compound tubuloalveolar glands, mainly mucous-like secretions
• Found below diaphragma urogenitale
• Open into the upper part of pars spongiosa urethrae

Paraurethral glands (Littré‘s)

• Minute mucous glands in the lamina propria

SEMEN – physiological composition

• Secretion formed by testicular fluid containing spermatozoa,
• secretion of the seminal vesicle, prostate, glandulae bulbourethrales

Question 7

Structure of the ovary

Development of the ovarian follicle, oogenesis

Answer 7

The female reproductive organs

• Can be divided into
  
  • Upper genital tract (i.e., uterus, fallopian tubes, ovaries, and cervix)
  • Lower genital tract (i.e., the vagina and vulva).
• Function:
  
  • These organs participate in several hormonal and mechanical pathways that are responsible for secondary sexual development and reproduction.

The ovaries

• Paired organs
• Responsible for:
  
  • Gametogenesis: Production of female gametes – oocytes
  • Sex hormone synthesis in females.
    
    • Estrogen
      
      • Promote growth and maturation of internal and external sex organs
      • Responsible for female sex characteristics which develop at puperty
      • Act on mamary glands to promote brest development
    • Progesterone
      
      • Prepaire internal sex organs (mainly uterus) for pregnancy by promoting secretory chnages in endometrium
      • Prepaire the mammry gland for lactation by promoting lobular proliferation ​

Main structure: (outer to inner)

• Germinal epithelium
  
  • The ovarian surface is covered by a single layer of cells called the germinal epithelium
  • single layer of cuboidal, and in some parts squamous cells: AKA germinal epithelium
  • Contiunous with mesothelium that covers the mesovarium
  • specialization of the peritoneal mesothelium
    
    • ​does not give rise to any oogonia
• Tunica albuginea
  
  • Dense, irregular connective tissue under germinal epithelium
  • Dense CT
• Parenchyma of the ovary consists of two zones:
  • Cortex
    
    • Located below the tunica albuginea
    • Contain overian follicles embedded in richly cellular CT
    • Scattered smooth muscle fibers are present in stroma around follicles
    • networks of reticular fibers and numerous spindle-shaped cells, arranged in irregular whorls. ????
    • Contains a great number of follicles in all stages of development.
• Medulla
  
  • Loose CT
  • Deep to the cortex is the highly vascularized, connective tissue core of the ovary, the medulla.
  • There is no distinct boundary line between the cortex and medulla, and these two regions blend together.

Development of the ovarian follicle, oogenesis

• In the first month of embryonic life, a small population of primordial germ cells migrates from the yolk sac to the gonadal primordia.
• There the cells divide and differentiate as oogonia .
  
  • In developing ovaries of a 2-month embryo, there are about 600,000 oogonia that produce more than 7 million by the fifth month.
  • Beginning in the third month, oogonia begin to enter the prophase of the first meiotic division but arrest after completing synapsis and recombination, without progressing to later stages of meiosis
  • These cells arrested in meiosis are called primary oocytes ​
• Each primary oocyte becomes surrounded by flattened support cells called follicular cells to form an ovarian follicle.
  
  • By the seventh month of development, most oogonia have transformed into primary oocytes within follicles.
  • Many primary oocytes, however, are lost through a slow, continuous degenerative process called atresia
    
    • Which continues through a woman’s reproductive life.
• At puberty the ovaries contain about 300,000 oocytes.
  
  • Because generally only one oocyte resumes meiosis with ovulation during each menstrual cycle (average duration, 28 days) and the reproductive life of a woman lasts about 30 to 40 years,
    
    • Only about 450 oocytes are liberated from ovaries by ovulation.
    • All others degenerate through atresia.

Follicular development

• Primordial follicles
  
  • Earliest stage of development
  • First appear in the 3rd month of development
  • Independent of gonadotropin stimulation
  • Found in stroma of cortex, just beneath tunica albuginea
  • Follicle structure:
    
    • Single layer of squamous follicle cells surrounds oocyte
    • Ouer surface: basal lamina
  • Oocyte structure:
    
    • (30 μm)
    • Large nucleus with well visible nucleolus,
    • Balbiani bodies: localized accumulation of Golgi membranes and vesicles, endoplasmic reticulum, numerous mitochondria, and lysosomes.
• Growing follicles, Primary
  
  • 1- Unilaminar primary follicle
    
    • Follicle structure:
      
      • Simple layer of cuboidal follicular cells
        
        • when cells become cuboidal, follicle is difined as primary)
      • Extracellular material accumulates and develops around the oocyte: zona pellucida
        
        • Composed of 3 classes of sulfated acidic ZP glycoprotiens:
        • ZP1, ZP2, ZP3 (inducer of acrosome reaction)​​
    • Oocyte Structure
      
      • 150 μm: oocyte enlarges
  • 2- Multilaminar primary follicle/ Late primary follicle
    
    • Follicle structure: ​
      
      • Single layer of follicle cells give rise to stratified epithlium:
        
        • Membrana granulosa: surrounding oocyte
      • Basal lamina remains the outer most layer
      • Gap junctions develop between granulosal cells
      • Granulosa cells proliferate: stromal cells
        
        • Cells that immediatly surrounding the follicle,
        • Form a sheath of CT cells: theca folliculi
          
          • ​Just external to the basal lamina
    • Oocyte is surrounded by
      
      • Zona pellucida,
      • Follicular cells (granulosa) are interconnected by gap junctions;
      • Theca folliculi
    • The primary follicle moved deeper into cortical stroma as it increases in size,
      
      • FSH, growth factorts and calcium are requried for growth
• Secondary follicle
  
  • Follicle structure: ​​
    
    • When the stratum granulosum reaches a thickness of 6 to 12 cell layers,
      
      • Fluid-filled cavities appear among the granulosa cells
    • As the hyaluronan-rich fluid called liquor folliculi continues to accumulate among the granulosa cells,
    • the cavities begin to merge, eventually forming a single, crescentshaped cavity called the antrum.
      
      • The follicle is now identified as a secondary follicle or antral follicle
    • The theca folliculi further differentiates into two layers:
      
      • The theca interna: highly vascularized layer of cuboidal secretory cells
        
        • Steroid-producing cells.
        • Large number of luteinizing hormone (LH) receptors.
        • In response to LH stimulation, they synthesize and secrete the androgens that are the precursors of estrogen.
        • In addition to secretory cells, the theca interna contains fibroblasts, collagen bundles, and a rich network of small vessels typical of endocrine organs.
      • The theca externa: is the outer layer of connective tissue cells.
        
        • It contains mainly smooth muscle cells and bundles of collagen fibers.
  • Oocyte
    
    • The eccentrically positioned oocyte
      
      • which has attained a diameter of about 125 um, undergoes no further growth.
• Mature/ graafian follicles
  
  • Follicle
    
    • Cumulus oophorus
      
      • A thickened mound of granulosa cells
      • Projects into the antrum.
      • Immediately surround the oocyte and remain with it at ovulation are referred to as the corona radiata.
      • The corona radiata
        
        • cumulus cells will become this after ovulation
        • Send penetrating microvilli throughout the zona pellucida to communicate via gap junctions with microvilli of the oocyte.
  • The mature follicle
    
    • has a diameter of 10 mm or more.
    • Because of its large size, it extends through the full thickness of the ovarian cortex and causes a bulge on the surface of the ovary.
    • As the follicle nears its maximum size, the mitotic activity of the granulosa cells decreases.
    • The stratum granulosum appears to become thinner as the antrum increases in size.
    • As the spaces between the granulosa cells continue to enlarge,
      
      • the oocyte and cumulus cells are gradually loosened from the rest of the granulosa cells in preparation for ovulation.
      • The cumulus cells immediately surrounding the oocyte now form a single layer of cells of the corona radiata.
      • These cells and loosely attached cumulus cells remain with the oocyte at ovulation.

Initiation of ovulation:

• In response to FSH,
  
  • The granulosa cells catalyze the conversion of androgens to estrogens,
  • Which in turn stimulate the granulosa cells to proliferate and thereby increase the size of the follicle.
    
    • Increased estrogen levels from both follicular and systemic sources are correlated with increased sensitization of gonadotropes to gonadotropin-releasing hormone.
  • A surge in the release of FSH or LH is induced in the adenohypophysis approximately 24 hours before ovulation.
    
    • In response to the LH surge,
      
      • LH receptors on granulosa cells are downregulated (desensitized),
      • and granulosa cells no longer produce estrogens in response to LH.
  • Triggered by this surge,
    
    • The first meiotic division of the primary oocyte resumes.
    • This event occurs between 12 and 24 hours after the LH surge,
      
      • Resulting in the formation of the secondary oocyte and the first polar body.
  • The granulosa and thecal cells then undergo luteinization and produce progesterone

Question 8

Uterus and oviduct

Endometrium and menstrual cycle

Answer 8

The female reproductive organs

• Can be divided into
  
  • Upper genital tract (i.e., uterus, fallopian tubes, ovaries, and cervix)
  • Lower genital tract (i.e., the vagina and vulva).
• Function:
  
  • These organs participate in several hormonal and mechanical pathways that are responsible for secondary sexual development and reproduction.

Uterine tube (fallopian tube, salpinx, Fallopia tube)

• Hollow pair tube 10–12 cm long
  
  • ​Extend bilaterally from the uterus twards the ovaries
• Function:
  
  • Transport ovum from ovary to uterus and provide the nesissary enviorment for fertalization and initial development of the zygote to the morula stage
• Parts:
  
  • Infundibulum with fimbriae
    
    • Adjacent to ovary
    • At distal end opens into peritoneal cavity
    • Proximal end communicates with ampula
  • Ampula
    
    • 2/3 of length
    • Widest part; most common site of fertilization
  • Isthmus: narrowest part
  • Intramuralis pars
    
    • Located in the myometrium of the uterus; connects the ampulla to the uterus

Wall of uterine tube:

• Mucosa
  
  • Simple columnar epithelium.
    
    • Cells:
    • Cilliated cells
      
      • Most numerous in infundibulum and ampula
    • Non cillated peg cells
      
      • Secratory cells that produce fluis that provides nutritive material for ovum
    • During the early proliferative phase of the menstrual cycle and under the influence of estrogen, the ciliated cells undergo hypertrophy, exhibit cilia growth, and become predominant.
    • In addition, there is an increase in the secretory activity of the nonciliated peg cells.
    • The epithelium of the uterine tube shows cyclic changes, and the proportion of ciliated and nonciliated cells varies with the stages of the menstrual cycle.
  • Lamina propria:
    
    • Loose connective tissue
  • Fine branched folds of loose connective tissue
    
    • Form an irregular lumen in the uterine tube that produces deep grooves between the folds
      
      • These folds become smaller as the uterine tube nears the uterus.
      • Numerous and complex in ampula, smaller in isthmus
• Muscular layer
  
  • Two smooth muscle layers,
    
    • Inner circular layer
    • Outer longitudinal layer
  • Interstitial connective tissue
    
    • Abundant between the muscle layers
      
      • As a result, the smooth muscle layers are not distinct. Numerous venules
    • Contain arterioles and venules
• Serosa
  
  • Of visceral peritoneum forms the outermost layer on the uterine tube,
  • It is connected to the mesosalpinx ligament of the superior margin of the broad ligament.

Uterus (uterus, meter, hystera)

• Hollow muscular organ with a thick wall located in a woman’s small pelvis.
• Pear-shaped shape and is slightly flattened on the back.
• Function:
  
  • Site of implantation of the fertilized ovum
  • Protects and supports the growth of the fetus
  • Site of menstruation; see physiology of the menstrual cycle.
• Dimensions: Vary according to the stage of life
  
  • Woman who has already given birth = multipara,
    
    • Dimensions are slightly larger
  • Woman who has not yet given birth = nulipara,
    
    • Dimensions are 8 x 5 x 2–3 cm (length x width x depth),

Parts of the uterus:

• Uterine fundus: superior, rounded aspect of the uterus
• Body
  
  • Uterine horns: site of the opening of the fallopian tubes bilaterally
  • Uterine cavity: triangular, continuous with uterine tube and internal os
• Isthmus:
  
  • Constriction between the body and the cervix
  • Corresponds to the level of the internal os of the uterus

​Uterine wall:

The wall of the uterus consists of three layers:

• Innner endometrium
• Middle layer of smooth muscle myometrium
• Outer serous membrane perimetrium

1- Endometrium

• ​Simple columnar epithelium
• Lamina propria:
  
  • Thick
  • loose connective tissu
  • Simple tubular glands.
  • Divided into 2 layers
    
    • Basalis layer
      
      • a narrow, deep
      • adjacent to the myometrium
    • Functionalis layer
      
      • Wider, superficial layer above the basalis layer that extends to the lumen of the uterus.

2- Myometrium

• Compact bundles of smooth muscle separated by thin strands of interstitial connective tissue with numerous blood vessels
• both longitudinal and transverse planes
• continues into muscle layer of the oviduct.

3- Parametrium

• Conective tissue forming uterine ligaments (lig. latum uteri, lig. teres uteri).
  
  • Uterine body: covered by peritoneal serosa
  • Anterior cervix and lateral uterine body: adventitia (not covered by peritoneum)

______________________________________________________

Functional Changes in Endometrium

The endometrium is further subdivided into two zones or layers:

• basalis layer
  
  • a narrow, deep
  • adjacent to the myometrium
• Functionalis layer
  
  • Wider, superficial layer above the basalis layer that extends to the lumen of the uterus.
• During the menstrual cycle, the endometrium exhibits morphologic changes that are directly correlated with ovarian function.
  
  • The cyclic changes in a nonpregnant uterus are divided into three distinct phases:
    
    • the proliferative (follicular) phase;
    • the secretory (luteal) phase;
    • and the menstrual phase.

Uterus: Proliferative (Follicular) Phase

• Under the influence of ovarian estrogen,
• The stratum functionalis increases in thickness
• The uterine glands elongate and follow a straight course to the surface.
• The coiled (spiral) arteries are primarily seen in the deeper regions of the endometrium.
• The lamina propria (2) in the upper regions of the endometrium :
  
  • is cellular and resembles mesenchymal tissue.
• The connective tissue in the basilis layer:
  
  • More compact and appears darker in this illustration.
• The endometrium continues to develop during the proliferative phase as a result of the increasing levels of estrogen secreted by the developing ovarian follicles.

Uterus: Secretory (Luteal) Phase

• Initiated after ovulation of the mature follicle.
• Reduced levels of circulating progesterone (and estrogen), as a result of the regressing corpus luteum, initiate this phase.
  
  • Decreased levels of these hormones induce intermittent constrictions of the spiral arteries and interruption of blood flow to the functionalis layer of the endometrium,
  • while the blood flow to the basalis layer remains uninterrupted.
• These constrictions deprive the functionalis layer of oxygenated blood and produce transitory ischemia,
  
  • Causing necrosis (death) of cells in the walls of blood
• The additional changes in the endometrium are caused by the influence of:
  
  • both estrogen
  • and progesterone
• that is secreted by the functioning corpus luteum.
• As a result,
  
  • the functionalis layer and basalis layer of the endometrium become thicker owing to increased glandular secretion and edema in the lamina propria
• The epithelium of the uterine glands
  
  • undergoes hypertrophy (enlarges) as a result of increased accumulation of the secretory product
  • also become highly coiled (tortuous), and their lumina become dilated with nutritive secretory material rich in carbohydrates.
• The coiled arteries continue to extend into the upper portion of the endometrium (functionalis layer) and become prominent because of their thicker walls.
• The alterations in the surface columnar epithelium (4), uterine glands and lamina propria characterize the functionalis layer of the endometrium during the secretory or luteal phase of the menstrual cycle.
• The basalis layer
  
  • Exhibits minimal changes.

Uterus: Menstrual Phase

• Begins when the ovulated oocyte is not fertilized and no implantation occurs in the uterus.
  
  • Reduced levels of circulating progesterone (and estrogen),
    
    • As a result of the regressing corpus luteum, initiate this phase.
• Decreased levels of these hormones induce intermittent constrictions of the spiral arteries and interruption of blood flow to the functionalis layer of the endometrium,
  
  • While the blood flow to the basalis layer remains uninterrupted.
• These constrictions deprive the functionalis layer of oxygenated blood and
  
  • Produce transitory ischemia,
  • Causing necrosis (death) of cells in the walls of blood vessels and degeneration of the functionalis layer in the endometrium.
• After extended periods of vascular constriction,
  
  • The spiral arteries dilate, resulting in the rupture of their necrotic walls and hemorrhage (bleeding) into the stroma.
  • The necrotic functionalis layer then detaches from the rest of the endometrium.
  • Blood, uterine fluid, stromal cells, secretory material, and epithelial cells from the functionalis layer mix to form the menstrual flow.
• The shedding of the functionalis layer of the endometrium continues until only the raw surface of the basalis layer is left.
  
  • The remnants of uterine glands in the basalis layer serve as the source of cells for regenerating the next functionalis layer.
  • Rapid proliferation of cells in the glands of the basalis layer, under the influence of rising estrogen levels during the proliferative phase,
  • resurface and restore the lost endometrial layer and start the next phase of the menstrual cycle.

Menstrual cycle

• Highly regulated, physiological process that makes conception and pregnancy possible.
• From the start of menstruation to its cessation (menopause),
  
  • Monthly menstrual bleeding (menses) is regulated by hypothalamic and pituitary hormones.
  • Even the smallest changes in hormone levels can result in menstrual cycle abnormalities.
    
    • A variety of conditions and factors (e.g., medication, stress) can cause such hormonal changes, which are not necessarily pathological.

The cycle

• The cycle lasts 21–35 days on average, with the first day of menstrual bleeding counting as day 1 of the cycle.
  
  • The cycle consists of two phases:
    
    • 1. Follicular phase : accounts for most of the variability in the length of the menstrual cycle
    • 2. Luteal phase : lasts 14–15 days
    • Menses last an average of 3–7 days, with an average blood loss of 35–50 mL.
• The cycle changes with age:
  
  • First few years following menarche → irregular menstrual cycles (caused by immaturity of the hypothalamic-pituitary-gonadal axis)
  • Menstrual cycles are longest at 25–30 years of age, with younger and older women having shorter cycles.

Days 1–14

Ovaries: follicular phase

• FSH stimulates the development of several follicles in the ovaries → granulosa cells of follicles produce estrogen → suppresses release of FSH via a negative feedback loop
• Selection of a dominant follicle (Graafian follicle)
• High levels of estrogen trigger a positive feedback loop → release of FSH → subsequent LH surge initiates ovulation

Endometrium: desquamation and proliferative phase

• Desquamation (menstruation at days 1–4)
  
  • Absence of a pregnancy → resolution of corpus luteum → progesterone concentration decreases → induces vasospasms in the uterine spiral arteries, ischemia, and sloughing off of the functional layer of the endometrium
  • Menses may actively be delayed if progesterone is administered in the second half of the menstrual cycle.
• Proliferation (days 4–14): growing follicles produce estrogen (granulosa cells express aromatase, which converts androgens to estrogens) → stimulates proliferation of the endometrium
  
  • Histology
    
    • Proliferation of endometrial epithelial cells (cells show high mitotic activity)
    • Endometrial glands are straight, tubular, and lined by simple columnar epithelium.
    • Stromal cells start to divide, enlarge, and accumulate glycogen.
    • Uterine spiral arteries start to regenerate and extend two-thirds of the way into the endometrium.

Days 14–28

Ovaries: luteal phase

• Ovulation: rupture of Graafian follicle → oocyte is released
• Following ovulation, the granulosa cells produce LH receptors → LH-induced transformation of the Graafian follicle into the corpus luteum → produces progesterone → inhibits LH release via a negative feedback loop
• If no pregnancy occurs → corpus luteum regresses

Endometrium: secretory phase

• Endometrial differentiation promoted by progesterone → preparation of the functional layer of the endometrium for oocyte implantation
• Histology
  
  • During ovulation: intracellular subnuclear vacuoles
  • Increased endometrial gland tortuosity
  • Glycogen-rich secretions
  • Edematous stromal cells
  • Uterine spiral arteries extend the full length of the endometrium.
• In the absence of pregnancy → ↓ progesterone levels → induces apoptosis of the functional layer of the endometrium (seen as shrinkage and fragmentation of endometrial cell nuclei) → menstruation

Question 9

Cervix uteri and vagina, structure and examination

Answer 9

The female reproductive organs

• Can be divided into
  
  • Upper genital tract (i.e., uterus, fallopian tubes, ovaries, and cervix)
  • Lower genital tract (i.e., the vagina and vulva).
• Function:
  
  • These organs participate in several hormonal and mechanical pathways that are responsible for secondary sexual development and reproduction.

Cervix and Vagina

Cervix

• Most distal aspect of the uterus and protrudes into the fundus of the vagina.
• Most of the uterine body and posterior supravaginal cervix are covered by peritoneum.
• Function:
  
  • Promotes entry of sperm into the uterus for fertilization
  • Allows menstrual blood to flow from the uterus into the vagina
  • The endocervix secretes a clear, alkaline fluid to facilitate the passage of sperm.
• Unlike the functionalis layer of the uterine endometrium, the cervical mucosa undergoes only minimal changes during the menstrual cycle and is not shed during menstruation.
• Structure
  
  • Supravaginal cervix: portion of the cervix superior to the vagina
  • Vaginal cervix: portion of the cervix that protrudes into the fundus of the vagina
  • Cervical canal
  • Cervical os: the opening of the cervix into the vagina
• The cervix is the lower, cylindrical part of the uterus.
• The cervix differs histologically from the rest of the uterus.
  
  • The endocervical mucosa is a simple columnar epithelium.
  • This mucosa is not thickened during the menstrual cycle and is not shed.
  • The endocervical mucosa doesn’t contain spiral arteries, and its thick lamina propria contains mucus secreting cervical glands.
• The product of the cervical glands changes during the menstrual cycle, under the regulation of progesterone
• • During ovulation the secretion is
• watery and more abundant,
• assisting sperm movement into the
• uterus. At other parts of the
• menstrual cycle the as the luteal
• phase the secretion is more viscous
• obstructing the sperm movement.
• • During pregnancy the glands proliferate and secrete a highly viscous mucus, forming a plug in the cervical
• canal.
• • The transformation zone is the area in the cervix in which the epithelium transitions from simple
• columnar to stratified squamous nonkeratinized (exocervical mucosa). This happens in the vaginal part
• of the cervix surrounding the external os.
• • The deeper wall of the cervix contains dense connective tissue with much less smooth muscle (in
• comparison to the rest of the uterus).
• • The cervix becomes very rigid during pregnancy and before labor it softens by a remodeling of the tissue,
• in a process involving macrophages.
• • Lymphatic nodules may be also present in the cervix lamina propria.
• **Nabothian cysts- usually appear when stratified squamous epithelium overlies the columnar. filled with mucus.
• The vagina is a fibromuscular structure that extends from the cervix to the vestibule of the
• external genitalia. Its wall has numerous folds and consists of an inner mucosa, a middle muscular
• layer, and an outer connective tissue adventitia. The vagina does not have any glands in its
• wall and its lumen is lined by stratified squamous epithelium.Mucus produced by cells in the
• cervical glands lubricates the vaginal lumen. Loose fibroelastic connective tissue and a rich vasculature
• constitute the lamina propria that overlies the smooth muscle layers of the organ. Like
• the cervical epithelium, the vaginal lining is not shed during the menstrual flow.