Male reproductive

From Iusmhistology

• started here on 04/06/11.

• State wide exam:
  • Previously the NBME exam had nothing to do with our histo course; there was lots of CMB, etc.
  • So now they make a customized NBME.
  • 100 questions
  • 2.5 hours (150 minutes)
  • Does not cover special senses.
  • We are the last of the centers to take the NBME exam.
  • How to study: use the high-yield materials; some have not studied and done just fine.
  • Review session on Wednesday before the exam.

Contents 1 Male reproductive 1.1 Anatomy review 1.2 Seminiferous epithelium 1.3 Spermatogenesis 1.3.1 Mitosis and Meiosis 1.3.2 Spermiogenesis 1.4 Sertoli cells 1.4.1 Blood testis barrier 1.4.2 Sertoli function stimulated by FSH 1.5 Leydig cells 1.6 Segments of the male reproductive tract 1.7 Accessory glands of the male reproductive tract 1.7.1 Seminal vesicles 1.7.2 Prostate 1.7.3 Bulbourethral glands 1.8 Ejaculation sequence 2 Lab

[edit] Male reproductive

[edit] Anatomy review

• The testes are egg-shaped organs covered with a cartilagenous capsule called the tunica albuginea.
• The testes are divided into lobules; lobule division is incomplete and achieved by the connective tissue septae.
  • There are approximately 250 lobules in the testis.
  • Each lobule has one or several seminiferous tubules.
• The mediastinum testis is where the vessels (blood and lymphatics), nerves, and efferent duct enter and exit the testis.
  • The mediastinum testis lies at the posterior aspect of the testis.
  • Note that the mediastinum testis is connective tissue while rete testis is a collecting tubule tissue.
• Seminiferous tubules are blind ended, highly coiled, and lined with spermatic epithelium.
  • It is within the seminiferous tubules that spermatogenesis takes lace.
  • The tunica propria is the outer wall of the seminiferous tubule and is made of smooth muscle and fibroblasts.

[edit] Seminiferous epithelium

• The seminiferous epithelium (the inside of the seminiferous tubule, recall) is a stratified epithelium and is responsible for generating male gametes.
• There are multiple types of spermatogonia in the seminiferous epithelium: type A and type B.
• Type A spermatogonia are stem cells.
• Type B spermatogonia are highly mitotic progenitor cells.
  • Type B spermatogonia are connected via cytoplasmic bridges which help synchronize maturation of developing spermatozoa.
• Note that we will not differentiate between type A spermatogonia and type B spermatogonia in lab.
• Spermatids remain in close physical contact with the Sertoli cells throughout development.

[edit] Spermatogenesis

• Recall the order cell names in spermatogenesis: type A spermatogonia -> type B spermatogonia -> primary spermatocyte -> secondary spermatocyte -> spermatid -> spermatozoa.
  • Primary spermatocytes are in the prophase of meiosis 1 and stick around for 20 days.
  • Secondary spermatocytes are relatively short-lived.
  • Note that spermatids shed their residual bodies as they become spermatozoa.
• Recall the order of divisions in spermatogenesis: mitosis, mitosis / differentiation, meiosis 1, meiosis 2, differentiation.
  • Note that mitosis from type A spermatogonia to type B spermatogonia will maintain the stem cell population and will occur more than once such that many type B spermatogonia are generated.

• As spermatogonia develop, they move from the basal compartment to the adlumenal compartment.
  • We call this adlumenal movement.
  • Cells of the basal compartment: type A and type B spermatogonia, primary spermatocytes
  • Cells of the adlumenal compartment: secondary spermatocytes, spermatids, spermatozoa

• Cells and processes: type A spermatogonia undergo mitosis to become ... type B spermatogonia undergo mitosis (and differentiation) to become ... primary spermatocytes undergo meiosis 1 ... secondary spermatocytes undergo meiosis 2 ... spermatids undergo morphologic modification (differentiation) ... spermatozoa.
  • Spermatocytogenesis includes all the steps that generate an increasing number of cells (that is, type A spermatogonia through generation of secondary spermatocytes); this makes sense because of the name "cyto" = cell and genesis = "origin of".
  • Spermiogenesis is the converse of spermatocytogenesis: spermeiogenesis is the maturation of existing cells into spermatozoa (from the secondary spermatocyte stage to the spermatozoa stage).

• It takes 60-70 days for spermatogonia to progress to spermatozoa.

[edit] Mitosis and Meiosis

• Recall that mitosis occurs when one 2N (diploid, like most cells of the body) cell makes a copy of the chromosomes (making it temporarily 4N--tetraploid) and divides the two copies up between two cells; both daughter cells are 2N.
• Recall that meiosis occurs when one 2N (diploid) cell makes a copy of the chromsosomes (making it temporarily 4N--tetraploid) and divides the two copies up between two cells--twice; all four daughter cells are 1N (haploid).
• So, primarly spermatocytes are the initial cell, secondary spermatocytes are the first generation of meiosis daughters, and spermatids are the second generation of meiosis daughters.
  • That is, secondary spermatocytes are the result of meiosis 1 (2N->4N->2N) and spermatids are the result of meiosis 2 (2N->1N).

[edit] Spermiogenesis

• Recall that spermiogenesis occurs on existing cells (spermatids) and does not generate any new cells.
• Spermiogenesis is characterized by morphological changes to the spermatid, that is the specialization / differentiation of the spermatid into the spermatozoa:
  • Loss of cytoplasm
  • Condensation of genetic material and nucleus
  • Formation of the acrosome
  • Formation of the axoneme
• Spermiogenesis has 3 phases: golgi phase, acrosomal phase, maturation phase.'
  • We will not be asked to identify the phase of a developing spermatid.

• Golgi phase:
  • The golgi phase generates the polarization of the cell; it is called the golgi phase because the golgi becomes the acrosome.
  • The enzymes like hyaluronidase and trypsin-like protease accumulate at one pole of the nucleus in a vesicle (which will become the acrosome).
    • This makes sense because upon greeting an oocyte, the spermatozoa will use the enzymes within the acrosome to digest away the shell of the oocyte so it can fertilize.
  • The centrioles (which will become the axoneme) migrates to the opposite pole as the enzyme vesicle.

• Acrosomal phase:
  • The acrosomal phase is characterized by ... the development of the acrosome.
  • The vesicle of enzymes flattens out over one pole of the nucleus.
  • The cell rotates such that the axoneme faces the lumen.

• Maturation phase:
  • The maturation phase is characterized by motile apparatus development and the capacity to fertilize.
  • The cell body is shed, generating the residual body; upon shedding, the sperm are released into the lumen of the seminiferous tubule.
    • Note that the sertoli cells clean up the residual bodies.
  • Note that during the maturation phase, the spermatids are not yet motile or fertile.
    • Though they may wiggle a little bit.

• Note that we can distinguish four parts of the spermatazoa: head, middle, principle piece, and end piece.
  • The Head contains the nucleus and acrosome.
  • The middle piece contains the mitochondria.
  • The principle piece is primarily axoneme.
  • The end piece is only the very last portion of the axoneme.

[edit] Sertoli cells

• Recall that Sertoli cells function as supporting cells for germ cells that generate spermatozoa.
  • Sertoli cells condition the microenvironment for gamete production.
  • Recall that Sertoli cells are physically close to the developing gametes.
• Sertoli cells are a tall, columnar epithelial cell.
• Sertoli cells are characterized by being tall, columnar epithelial cells with a large, indented euchromatic nucleus, and lots of eosinophilic cytoplasm.
• Neighboring Sertoli cells within a region have gap junctions which suggest that Sertoli cells are coordinated within their region.
  • Coordination through gap junctions would explain the fact that different regions of the seminiferous epithelium (which includes sertoli cells and spermatogonium) are at different stages of spermatid development. (That is, while one place may have a batch of spermatids going through morphological changes to be come spermatozoa, the neighboring region could have a group of primary spermatocytes undergoing meiosis 1 to generate secondary spermatocytes.)
  • Recall that it takes about 70 days for a spermatogonium to generate spermatozoa.

• stopped at minute 31.

[edit] Blood testis barrier

• It is important that the developing spermatozoa be kept separate from the blood supply because antibodies native to the pt can attack the developing spermatozoa because of immunologically active proteins generated through chromosomal recombination of meiosis 1.
  • The capillaries of the testes are fenestrated; such a capillary provides little to know barrier against antibodies.
• Sertoli cells of the seminiferous epithelium form tight junctions between one another to keep immunoglobulins in the blood from entering the lumen of the tubule.
  • Note that these tight junctions of the Sertoli cells are on the lumenal side of the spermatogonia.
  • These tight junctions define the two compartments: basal compartment and adlumenal compartment.
• Recall that spermatogonia through the primary spermatocytes are in the basal compartment and secondary spermatogonia through spermatozoa are in the adlumenal compartment.

• Occasionally, cells that should reside in the adlumenal compartment and be separate from immunological agents are detected and the ensuing immunological response results in infertility.

[edit] Sertoli function stimulated by FSH

• Recall that the anterior pituitary releases FSH which binds to the FSH receptor on Sertoli cells.
  • For related recall, LH is released by the anterior pituitary to bind on LH receptors of the Leydig cells found in the interstitium between the seminiferous tubules.
• FSH signaling on Sertoli cells causes phagocytic activity and production of several secretions.
• Secretions of the Sertoli cells:
  • Activin and Inhibin: stimulate and inhibit the anterior pituitary cells to release FSH.
  • Androgen binding protein (ABP): secreted into the lumen of the seminiferous tubule, binds up and concentrates testosterone.
  • Tubular fluid: lubrication.
• Phagocytic activity of Sertoli cells is responsible for degrading residual bodies and malformed spermatozoa.

[edit] Leydig cells

• Leydig cells produce testosterone upon signaling from the anterior pituitary via LH.
  • Recall that testosterone negatively feeds back on the hypothalamus.
  • Note that Leydig cells do not secrete activin or inhibin.
• Leydig cells are found in clusters in the peritubular interstitium of the testis, between the seminiferous tubules.
  • Recall that Leydig cells are often found near capillaries.
• Leydig cells are characterized by eiosinophilicism, lots of sER, mt with tubular cristae, and a lack of secretory vesicles.
  • Regarding lots of sER, recall that steroids are generated in sER.
  • Regarding a lack of secretory vesicles recall that steroids can pass directly through the membrane and therefore need not vesicular secretion.
  • By transmission EM, one can also discern crystalline inclusions.

• Leydig cells are "transiently" active during development and then initiate full activity at puberty.

• Recall that Sertoli cells generate ABP (androgen binding protein) upon FSH signaling and Leydig cells produce testosterone upon LH signaling.
• It is by the parallel production of ABP and test (by Sertoli and Leydig cells) that testosterone is effectively delivered to the male reproductive tract.

[edit] Segments of the male reproductive tract

• The male reproductive tract begins at the seminiferous tubules and runs to the penile urethra.
• Seminiferous tubules -> tubuli recti (straight tubules) -> rete testis -> efferent ductules -> epididymal ducts -> ductus deferens (vas deferens) -> ejaculatory duct -> prostatic uretral -> membraneous urethra -> penile urethra.
  • The seminiferous tubules reside in the lobules of the testis.
  • The seminiferous tubule runs posteriorly and medially (toward the mediastinum) to the rete testis via the tubuli recti.
  • The rete testis are a collecting system of the tubuli recti that dump into the efferent ductules.
  • Efferent ductules (recall that the "e" of efferent means exiting) allow exit of the fluid to the epididymal duct (e-duct -> e-duct).
  • The epididymal duct leads to the organ called the epididymis, which lies on the posterior, caudal aspect of the testis.
  • Fluid travels from the epididymis superiorly via the ductus deferents.
  • The tract becomes the ejaculatory duct once the seminal vesicle has joined; this makes sense if you think "now that we have seminal secretions (60% of the fluid) we're getting ready for ejaculation).
  • The rest of the tract is the urethra and then named based on the structure through which the tract is laid: the prostate, then the membranous part of the penis, and then penis proper.

Where do basal cells and principal cells start?

• Straight tubule (tubuli recti)
  • As the name implies, these are relatively straight tubules.
  • Contributes to fluid
  • Cuboidal to columnar
  • Contains the highest density of Sertoli cells

• Rete testis
  • This is an elaborate network of channels.
  • Contributues to fluid
  • Has an irregular epithelial morphology: squamous, cuboidal, columnar.
  • Has a fibrous stroma

• Efferent ductule
  • The efferent duct connects the rete testis to the epidiymal duct and really does "exit" the testis proper and pass through connective tissue like the tunics.
  • Like the rete testis, the efferent ductule has an irregular epithelial morphology and also has ciliated, pseudostratified cells.
    • These ciliated pseudostratified cells are called principal cells and are found as clusters of columnar cells surrounded by short cells.
    • These cells are the only ciliated cells of the male genital tract; it even makes a bit of sense that these are ciliated because they are passing through a sturdy connective tissue structure.
  • The short cells that surround the columnar cells are absorptive cells.

• Ductus epididymis
  • Leads to the organ called the epididymis.
  • The ductus epididymis is characterized by an pseudostratifed columnar epithelium, stereocilia, and a prominent muscularis layer.
  • The ductus epidiymis is pseudostratified epithelium (like the efferent ductule) and has stereocilia (which are different than cilia!).
    • Note that stereocilia are not like cilia because they don't move and they are not like microvilli because they are not that small.
  • The ductus epididymis is characterized by basal cells and principle cells.
    • Basal cells are regenerative.
    • Principal cells are secretory / absorptive.
  • The ductus epididymis has a prominent muscularis layer that thickens distally and changes from just a circular layer to an inner circular and outer longitudinal layer.
  • The functions of the ductus epididymis: absorb 90% of the tubular fluid, secrete factors that mature and capacitate sperm, and phagocytize cellular debris.

• Ductus deferens (vas deferens)
  • The ductus deferens is characterized by a pseudostratified columnar epithelium, abundant sympathetic innervation, and three layers to the muscularis.
  • The ductus deferens is pseudostratified (like the efferent ductule and ductus epididymis) and has stereocilia (like the ductus epididymis).
  • The muscularis has now added an inner longitudinal muscle layer to the ductus epididymis's inner circular and outer longitudinal.
  • The sympathetic innervation will be important for ejaculation which is facilitated by contraction of the ductus deferens's muscularis.
    • Recall that Point and Shooting require Parasympathetic and Sympathetic innervation.
  • The ductus deferens runs within the spermatic cord.

• Ejaculatory duct
  • The ejaculatory duct begins where the vas deferens (ductus deferens) joins the seminal vesicle.
  • Bilateral ejacualtory ducts (one from each testis) enter the prostate.

• Membranous urethra
  • The membranous urethra is characterized by a pseudostratified epithelium that transitions to a stratified columnar epithelium.
  • The membranous urethra crosses the muscular UG diaphragm.

• Penile urethra
  • The penile urethra is characterized by a pseudostratified epithelium that transitions to a stratified columnar epithelium, perhaps continuing on to stratified squamous epithelium at the top.
  • The penile urethra is also characterized by the presence of urethral glands which are clusters of mucus cells in the mucosa.

Section	Epithelium	Appendages	Muscularis
Seminiferous tubule	stratified	none	none
Tubuli recti	cuboidal -> columnar	none	none
Rete testis	irregular: squamous, cuboidal, columnar	none	none
Efferent ductule	pseudostratified	cilia	none
Ductus epididymis	pseudostratified	sterocilia	circular -> circular (inner) + longitudinal
Ductus deferens	pseudostratified columnar	stereocilia	longit (inner) + circular + longit
Ejaculatory duct	pseudostratified columnar	?	?
Prostatic urethra	pseudostratified -> simple columnar
Membranous urethra	pseudostratified -> stratified columnar	none	longit (inner) + circular + longit
Penile urethra	pseudostratified -> stratified columnar -> stratified squamous	none	longit (inner) + circular + longit

[edit] Accessory glands of the male reproductive tract

[edit] Seminal vesicles

• Seminal vesicles (paired bilaterally) are responsible for producing the largest portion of the semen.
• Seminal secretions are rich in fructose (for energy), prostaglandins, amino acids, and ascorbic acid.
  • This generates a viscous mucoid secretion.
• The seminal vesicle has plenty of smooth muscle with which to force this secretion out into the ejaculatory duct.
• Seminal vesicle function and growth is mediated by testosterone.
• The vesicles are blind-ended pouches near the prostate and ductus deferens.
• Seminal vesicles are lined with pseudostratified columnar epithelium.
  • This makes sense because they pump semen out into the GU tract at the ductus deferens and ejaculatory duct, both of which are pseudostratified.
• The seminal vesicles have mucosal arches which are highly folded, convoluted walls.

[edit] Prostate

• The prostate as an organ surrounds the base of the bladder.
• The prostate generates a secretion that becomes part of the semen and serves to condition the environment of the famale GU tract.
• The fribromuscular stroma surrounding the prostate is important for proper discharge of prostatic secretions during ejaculation.
• The prostatic secretion is a water, acidic mix of factors like zinc and fibrinolysin.
  • Zinc inhibits macrophage activity.
  • Fibrinolysin inhibits clot formation in the uterus.
• The prostate as a gland has alveoli connected via tubules; the tubules converge to generate a group of ducts that dump into the urethral crest.
  • The urethral crest receives the ejaculatory ducts and becomes the prostatic urethra.
  • The epithelium within the gland is irregular: pseudostratified to simple columnar.
• Corpora amylacea is a concentration of glycoprotein-rich secretion in the lumen of the gland that stains eosinophilic (because of the "protein-rich" part).

• The prostate has three concentric-like zones: central zone, transitional zone, and peripheral zone.
• The central zone of the prostate is the most medial and contains primarily periurethral mucosal glands.
  • The central zone often stains the lightest of the zones.
• The transitional zone of the prostate is the middle zone and contains periurethral submucosal glands.
  • Note that the central and transitional zones are most commonly associated with benign prostatic hypertrophy (BPH).
• The peripheral zone of the prostate is the outer zone, contains the main glands, is called the prostate proper, and is commonly involved with malignancies.
  • The peripheral zone is often involved with prostate cancer.

[edit] Bulbourethral glands

• The bulbourethral glands produce a secretion for lubricating the male GU tract for ejaculation.
• The secretion of the bulburethral gland is clear and viscous.

[edit] Ejaculation sequence

• Ejaculation has a particular series of events regarding all these secretions:
  • Bulbourethral glands discharge to lubricate.
  • Prostate releases contents (via contraction of the fibromuscular stroma).
    • Recall that the prostate's secretions serve to condition the female GU tract.
  • The ductus deferens receives sympathetic stimulation to contract its muscularis (1->2 layers), thus pushing spermatozoa into the urethra.
  • Seminal vesicles discharge their contents thus clearing the urethra by pushing semen distally.

• stopped here on 04/06/11.

[edit] Lab

• In the seminiferous tubules:
  • Spermatogonia are right on the BM.
  • Primary spermatocytes are light staining with dense chromosomes just adlumenal to the spermatogonia.
  • We won't have to ID secondary spermatocytes.
  • Spermatids are round cells with dense nucleus.
  • Spermatozoa are elongated cells embedded in Sertoli cells.
  • Sertoli cells have abundant cytoplasm.

• ID straight tubules by the presence of Sertoli cells.
• Ductus epididymis has very tall cells with cilia.
• Ductus deferens ID by stereocilia and three layers of muscle.
• Seminal gland: mucosal arches
• Prostate is ID'd by corpora amylacea (a concentration of glycoprotein-rich secretion in the lumen of the gland that stains eosinophilic).