Male reproductive

From Iusmhistology

Revision as of 18:43, 6 April 2011

• started here on 04/06/11.

Male reproductive

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.

Seminiferous epithelium

• The seminiferous epithelium (the inside of the seminiferous tubule, recall) is a stratified epithelium.
• 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.

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 compatment.
  • 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.

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).

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.
• Golgi phase:
  • The golgi phase generates the polarization of the cell.
  • 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 during the maturation phase, the spermatids are not yet motile or fertile.

• 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.

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.

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.

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.

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.

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 -> 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 can be considered synonymous with 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 (75% 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.

• Straight tubule
  • As the name implies, these are relatively straight tubules.
  • Contributes to fluid
  • Cuboidal to columnar
  • Contains 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.
  • The short cells that surround the columnar cells are absorptive cells.