Male Reproductive System II Flashcards
What is the typical sequence of spermatogenesis?
- Starting at the basement mb and moving towards the lumen, basally, Spermatogonia (A”1”) -> 2 Spermatogonia (A”2”) -> 4 Spermatogonia (A”3) & so on during PROLIFERATION (# of divisions depends on sp)
Spermatogonia (A”3”) -> Spermatogonia (A”4”) -> Spermatogonia (I) -> Spermatogonia (B) -> then adluminally -> primary spermatocytes -> meiosis I -> secondary spermatocytes -> meiosis II -> Spermatids -> undergo DIFFERENTIATION
What is another name for proliferation?
spermatocytogenesis
what is another name for differentiation?
spermiogenesis
What do male germline stem cells do?
- thread 1 generation to the next
- include PGCs, gonocytes, SPERMATOGONIAL STEM CELLS (SSCs)
What are spermatogonial stem cells?
- can self-renew & produce differentiated germ cells
- are the only adult stem cells that can pass on genes to the next generation
What are the two proposed models for the formation of spermatogonial stem cells (SSCs)?
- all gonocytes are the same but some (randomly) transition to SSCs, which can renew & give rise to progenitors, while others directly give rise to differentiating spermatogonia
- PGC -> gonocyte -> (SSC -> progenitor -> A”1” -> sperm) OR (A”1” -> sperm) - different types of gonocytes are responsible for forming the SSC pool, initial progenitor population, & initial differentiating spermatogonial population
- PGC -> Gonocyte -> (SSC -> progenitor -> A”1” -> sperm) OR (progenitor -> A”1” -> sperm) OR (A”1” -> sperm)
What are the possible outcomes of SSC division?
- self-renewal capability is important in ensuring SSC pool maintenance
- self-renewal & maintenance must be kept in balance, or it may lead to either germ cell tumour or depletion of SSCs
- DURING NEONATAL DEVELOPMENT & FOR REGENERATION of spermatogenesis after cytotoxic insult, SYMMETRICAL SELF RENEWAL may predominate
Symmetrical self renewal:
SSC -> SSC & SSC - DURING STEADY-STATE SPERMATOGENESIS, BALANCE OF SYMMETRICAL SELF-RENEWAL & SYMMETRICAL DIFFERENTIATION may occur @ defined frequencies
Symmetrical differentiation:
SSC -> committed progenitor spermatogonia - RECENT EVIDENCE SUPPORTS ASYMMETRIC DIVISION of an SSC to produce 1 new SSC & 1 transient amplifying progenitor
Asymmetric division:
SSC -> (SSC) OR (transient amplifying progenitor spermatogonia -> committed progenitor spermatogonia) OR (transient amplifying progenitor spermatogonia -> transient amplifying progenitor spermatogonia -> committed progenitor spermatogonia)
Process of A”1” to spermiation?
Spermatogenic stem cell (pool of undifferentiated spermatogonia -> transit amplifying progenitor cells ) -> differentiating spermatogonia (8.6 days) -> preleptotene -> meiosis -> spermiogenesis -> spermiation
(approximately 35 days from A”1” to spermiation)
What happens at the undifferentiated spermatogonia stage?
- spermatogonia classified into undifferentiated & differentiating
- in rodents & most domestic spp, spermatogenesis starts w/ division of SPERMATOGONIA TYPE A”single” (A”s”)
- divide to form 2 new A”s” for self-renewal or a connected pair called A”pair” (A”pr”) for differentiation
- in rodents, further divisions lead to formation of type A”aligned” (A”al”) which remain as chains of 4, 8, or 16 cells
- UNDIFFERENTIATED SPERMATOGONIA (TYPES A”s”, A”pr”, & A”al”) HAVE SIMILAR CELLULAR MORPHOLOGY
- A”s” are rare & relatively quiescent & represent ‘TRUE SSC’
- A”pr” & A”al” cells may have some SSC potential but are on way toward differentiation & called ‘TRANSIT AMPLIFYING PROGENITOR CELLS’
What are differentiating spermatogonia?
- Retinoic acid causes A”al” to transition (w/o cell division) to A”1” to start differentiation
- involves major changes in morphology & mitotic behaviour
- then 5 synchronized cell divisions to form A”2”, A”3”, A”4” intermediate (In), & B-spermatogonia
- DIFFERENTIATING SPERMATOGONIA include A”1-4”, I, & B-spermatogonia
- B-spermatogonia must physically pass through the blood-testis barrier before further germ cell differentiation
What are primary & secondary spermatocytes?
- once in adluminal compartment, B- spermatogonia divide again to produce 2 PRIMARY SPERMATOCYTES that immediately enter the 1st phase of meiosis
- during the long prophase of 1st meiosis, DNA undergoes complete replication to form tetrads, followed by crossing over of homologous chromosomes to ensure genetic heterogeneity of gametes
- primary spermatocytes go through 5 stages, PRELEPTOTENE, LEPTOTENE, ZYGOTENE, PACHYTENE, & DIPLOTENE
- @ end of 1st meiosis, each primary spermatocyte has produced 2 SECONDARY SPERMATOCYTES (haploid, N), which are relatively short-lived & immediately undergoes the second meiotic division
How are round & elongating/elongated spermatids formed?
- @ end of Meiosis II, each secondary spermatocyte has produced 2 haploid ROUND (spherical) SPERMATIDS
- no further cell division will occur
- testosterone drives round spermatids to undergo extensive morphological differentiation known as SPERMIOGENESIS
- which leads to formation of ELONGATING/ELONGATED SPERMATIDS
- retinoic acid causes spermatozoa to be released into lumen of the seminiferous tubule during SPERMIATION process
What is differentiation or spermiogenesis?
- extensive morphological changes occur to turn a round spermatid into a sperm
- these changes include: formation of acrosome, condensation of nuclear material, outgrowth of a motile tail, & loss of excess cytoplasm, organelles, water (volume in later maturation phase is 20-30 % of a cap phase spermatid)
- can be divided into 4 phases (golgi phase -> cap phase -> acrosomal phase -> maturation phase)
What is the golgi phase?
- newly formed spermatid is spherical & has a well-developed Golgi apparatus
- small golgi vesicles fuse to form “PROACROSOMIC” secretory granules & centrioles start migrating to opposite side
- ACROSOMAL VESICLE (granule is formed), PROXIMAL CENTRIOLE (PC; will give rise to attachment point of tail), DISTAL CENTRIOLE (DC; will give rise to axoneme)
What is the cap phase?
- golgi migrates to caudal pole & distal centriole (DC) forms AXONEME (AX) or flagellum
- acrosomic vesicle flattens & begins to form a cap & CAP has an outer acrosomal membrane (OAM) & an inner acrosomal membrane (IAM) & enzymes
What is the acrosomal phase?
- nucleus begins to elongate & acrosome covers most of its anterior & MANCHETTE forms from caudal half & extends down
- neck & annulus are formed, all components still w/in cytoplasm
What is the maturation stage?
- mito form a spiral assembly around the flagellum that defines the middle piece
- POSTNUCLEAR CAP is formed from manchette microtubules
- ANNULUS forms the junction btwn the middle piece & the principal piece
How do sperm vary in length btwn spp?
- 50 microm in humans
- 60 in boar & stallion
- 75 in Ru
- 150-250 rodents
What 2 parts do the sperm seem to only consist of under a light microscope?
head & tail
What does the post-nuclear cap consist of & what does it help evaluate?
fibrous sulfur-rich proteins (stain intense w/ eosin-bromophenol blue in dead sperms, helps in evaluating the quality of the ejaculate)
What is the structure of the sperm head?
- head differs in different spp (generally spatula shaped in most but in rodents is sickle shaped)
- nucleus is oval, flat, & covered by a nuclear membrane
- chromatin is compacted & inactive due to high keratinoid proteins
- anterior 2/3rds of nucleus is covered by acrosome
what is an acrosome?
membrane covered lysosome containing hydrolytic enzymes (ex: acrosin, hyaluronidase, zona lysin, esterases, acid hydrolase)
what is an acrosome reaction?
during fertilization acrosome undergoes a specialized exocytosis
What is the post-acrosomal sheath?
region contains receptors for recognition of homologous oocyte
What is the structure of the sperm tail?
- tail is composed of capitulum, middle piece, principal piece, & terminal piece
What is the capitulum of the sperm tail?
fits into the implantation socket of the head
What is the middle piece of the sperm tail?
- has laminated columns, gives side-to-side flexibility to neck
- 9 course outer fibers
- axoneme composed of 9 pairs of microtubules (DOUBLETS) around 2 central filaments
- all covered by a helical mitochondrial sheath
What is the principal piece of the sperm tail?
forms majority of tail & continues to almost the end of the flagellum
What is the terminal piece of the sperm tail?
is where only microtubules remain
When do the stages of spermatogenesis take place?
- sperm production takes time & in non-seasonal males should be continuous
- before 1 spermatogenic series is completed, generally 4 or more new series are initiated
- all descendants of B-spermatogonia develop synchronously
- successive generations follow each other
- so spermatogenic cycle is divided into stages or cellular associations
- these are arbitrarily defined associations that transition 1 to the next at predictable intervals
- identical associations are found in cross sections
- ex: in bulls, rams, & sw there are 8 stages
What are the stages along a seminiferous tubule?
- @ any given cross section along a seminiferous tubule a different stage of cycle can be seen
- each stage follows or precedes adjacent stages
- complete sequence of stages (I through VIII) along a length of tubule is called a spermatogenic wave
- spermatogenic wave in bulls is ~10 mm long
How are LH & testosterone linked?
- each LH pulse drives a pulse of testosterone release by Leydig cells
- each remains high in serum for ~0.5-1 hr
How is spermatogenesis regulated by hormones?
- involves interplay btwn endocrine & paracrine/autocrine systems
- FSH acts on Sertoli cells to promote their function & facilitate spermatogenesis
- LH acts on Leydig cells to stimulate production of testosterone
- testosterone & inhibin act through a negative feedback mechanism to temporarily inhibit further release of GnRH, FSH, & LH
- FSH increases proliferation of spermatogonia
- w/in tubules, FSH receptors are only found on Sertoli cells, suggesting indirect FSH effects on germ cells
- FSH has little or no direct effect on completion of meiosis & spermatogenesis
- testosterone is crucial for transition of spermatocytes to spermatids
- owing to countercurrent system of pampiniform plexus, testosterone in testis is 100-500x higher than in circulation
- both testosterone withdrawal & lack of androgen receptors can result in lack of post-meiotic germ cells
- similar to FSH, any effect of testosterone on germ cells is indirect & mediated through somatic cells
- androgen receptors are absent in germ cells but abundant in Sertoli, peritubular myoid, & Leydig cells
- E”2” is converted from testosterone by aromatase in Sertoli cells
- lack of ERalpha or aromatase leads to spermatogenesis impairment in mice
