#13349 - Testes And Male Tract - Organisation of the Body

Testes and male tract

Male strategy

-males mate opportunistically from puberty to old age- testis produces large number of active spermatozoa continuously

-this requires continuous division of stem cells- the development of 1 spermatazoon takes more than days

Structure of testis

-Made of seminiferous tubules & interstitum

-Seminiferous tubules: 3 stages, increase in number of cells by mitosis, reduction in the number of chromosomes by meisosis, production of mature sperm from spermatids by spermiogenesis

-Interstitum: Leydig cells, Blood, nerves, lymph vessels

Function: Production of spermatozoa, male sex hormones

Development: Expression of SRY protein within somatic support cells of the XY gonad differentiate into sertoli cells and envelop into germ cells

-7^th week: sertoli cells with interstitial cells of the gonad, organise to form testis cords

-Puberty: testis cords become canalised (hole) and differentiate into semineferous tubules. Adjacent to the mesonephros, sertoli cells organise into a set of thin walled ducts called rete testis- these connect the semineferous tubules with mesonephric tubules

-the mesonephric duct develops into the epididymis, spermatic ducts/vasa deferens, seminal vesicles

Epididymis: continued maturation of released spermatozoa, it is a single long and very coiled tube

Vas deferens: transports spermatozoa, stores them in its ampulla, contracts in response to NA/ATP stimulation

-coelomic epithelium, separated from testis cords by an intervening layer of connective tissue called tunica albuginea

Spermatogenesis

-Primordial germ cells migrate into the gonad during embryogenesis- these cells immature germ cells/spermatogonia – migratory pathway important- teratoma

3 months postnatal- differentiate into type A spermatogonia (diploid)

-At puberty and continuing throughout life, spermatogonia lie next to the basement membrane of stratified epithelial lining of seminiferous tubules- divide mitotically- diploid complement of 46 chromosomes-

-After puberty: Further mitosis into spermatogonia B (committed sperm cell) and replenishes stem cell pool, spermatogonia a

Meiosis

-Spermatogonia undergo meiosis: Primordial germ cells contain 23 pairs of chromosomes

- primary spermatocytes undergo meiosis 1 to form secondary spermatocytes

Meiosis 1:

-DNA replication, converts diploid cell from 2N to 4N- marks the beginning of spermatogenesis, spermatogonium is called the primary spermatocyte

-Prophase: chromosomes condense into double stranded structures, homologous pairing centromere to centromere to form a structure called chiasma (4 chromatids, two centromeres, two chromosomes)

-chiasma formation makes it possible for two homologous chromosomes to exchange segments of DNA by crossing over- recombination of genetic material between maternal and paternal chromosomes is random- increases the genetic variability of gametes

-Metaphase, 4 stranded chiasma organised on the equator of a spindle apparatus

-Anaphase- one double stranded chromosome of each homologous pair is distributed to two daughter nuclei

-Daughter nuclei are 2N, but half the number of chromosomes- after daughter nuclei form the cell itself divides- undergoes cytokinesis- produces secondary spermatocytes

Meisosis 2:

-No DNA replication occurs

-Prophase : 23 double stranded chromosomes condense

-Metaphase: line up, centromeres replicate

Anaphase: double stranded chromosomes are pulled apart into 2 single chromatids- one of which is distributed to each of the daughter nuclei

Forms Definitive spermatocytes/spermatids – early formed spermatids are round

-Cell divisions are incomplete- cytoplasm linked between the spermatids form syncitium- differentiate synchronously - can transfer mRNA and proteins between haploid cells, meosis, spermatogenesis, also junctional contacts between spermatids and sertoli cells

-Spermiogenesis Differentiation of the Spermatids into sperm cells, final part of spermatogenesis and compromises following individual processes that partially proceed at the same time

i) Nuclear condensation: Thickening and reduction of nuclear size, due to small cell size of spermatozoa -Spermatid DNA undergoes packaging and becomes highly condensed- DNA packaged first with specific nuclear basic proteins, replaced with protamines during spermatid elongation, DNA is arranged in an annulus- tightly packed chromatid is transcriptionally inactive

ii)Acrosome formation: Forming the cap/acrosome contains the enzymes that play an important role in penetration through zona pellicuda of the oocyte- Golgi complex secretes vesicles containing Lysosomal (Hyaluronidase) enzymes which merge into a larger vesicle and lies close to cell nucleus- inverts itself like a cap over the largest part of the nucleus

– EM, looking from above its oval, pear sheaped if seen on lateral view- nucleus and acrosome form the sperm cell’s head that is bound to the midpiece by a short neck

iii) Flagellum formation: Generation of the sperm tail- Future axonemal structure grows out of the distal centriole, consists of a bundle of 9 peripheral double microtubule, 2 single ones in the centre- axenome consists of dynein arms, anchored to a doublet microtubule- by walking along an adjacent microtubule- dynein motors can cause microtubules to slide against each other- synchronised fashion- axoneme is pulled down- flagellar beating

Mutations in dyenin arms- primary ciliary dyskinesia: imotility in sperm- infertility

- rotation of the nucleus, acrosomal vesicle- flagellum primordium comes to lie on the opposite side of the acrosome during this phase the spermatozoa orientate themselves so that their tails point towards the centre of the lumen away from the epithelium

-Flagellum has four parts

-Neck- contains two centrioles

-Midpiece: sheath of ring shaped mitochondria, grouped around the axenome to provide energy for flagellar movement

-Principle piece: Fibrous sheath around the axenome

-End piece: consists only of the 9 + 2 structure of the axenome

iv) Cytoplasm reduction: Excess cytoplasm, residual body- phagocytosis of Sertoli cells

-As maturation progresses, the cells are displaced towards the lumen of tubule

v) Cell membranes also gain ZP3 receptors: can be idnetifed with an antibody,

- Sertoli cells are key in differentiation of gametes- maturing spermatocytes and spermatids are connected to sertoli cells by intercellular junctions, cytoplasmic processes called tubulobulbar complexes that extend into sertoli cells

-Cytoplasm of developing gametes shrinks dramatically during spermiogenesis- bubulobulbar complexes are through to provide a mechanism by which excess cytoplasm is transferred to sertoli cells

-As cytoplasm is removed spermatids undergo dramatic changes in shape and internal organisation that transform them into spermatozoa

Spermatazoon: Head (condensed nucleus, capped by apical vesicle filled with hydrolytic enzymes), midpiece contains large helical mitochondria, long tail contains microtubules

- mature sperm must have haploid complement of DNA, be motile, have receptors for zona pellicuda and oocyte, be able to penetrate zona pellicuda, be capable of activating oocyte.

Spermiation: Mature spermatozoa are released from protective Sertoli cells into the lumen of the seminiferous tubule. The non motile spermatozoa are now mature but lack motility- they are transported into Epidydimis in testicular fluid secreted by sertoli cells- peristalsic contraction

-Spermatids differentiate to form spermatozoa, unlike female ALL haploid cell produced fertilise the egg

-Spermatogenesis from spermatogonia to spermatozoa takes 60 days, new cohorts start to form every 12 days. At any one point in the epithelium- there are cells from 4 different cohorts- stage refers to hisological appearance (maturation, release, elongation, grouping)

Spermatozoa abnormalities

-Errors in spermatogenesis/spermiogenesis- common- examination of sperm sample- some sperms are small, narrow, double/triple heads, acrosomal defects and double tails- larger number of abnormal spermatozoa/ teratospermia can be associated with infertility

Arrangement of seminiferous tubule

Cells are arranged in coloumns

-Base- basal lamina and myoid cells which secrete the extracellular matrix

-Attached to the basement membrane are Sertoli cells- large polyhedral cells- extend from the basemement membrane to the lumen-> very tight junctions between sertoli cells separate the basal compartment from the luminal compartment. Sertoli cells maintain the luminal environment + support spermatogenesis (sustenacular cells) – secrete nutrients, absorb waste and phagocytose defunct sperm

-Sertoli cells also form the Blood testis barrier- prevents the entry of immune cells, which would break down the sperm. Spermatogenesis starts at puberty, long after development of intolerance has ended- so sperm components are foreign

Spermatogonium ( primary spermatocyte secondary spermatocyte spermatid (can be seen as Early spermatid, which is round or Late spermatid which is differentiating...