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Male Hypothalamic- Pituitary-gonadal Axis: Hormone Control
- hypothalamus releases hypothalamic gonadotropin-releasing hormone (GnRH)
- GnRH mediates the episodic release of the gonadotrophins (LH & FSH) from the anterior pituitary
- LH acts on Leydig cells
- FSH acts on Sertoli cells
What do Leydig cells do after stimulation by LH?
they produce testosterone (androgen biosynthesis) which activates genes in Sertoli cells that promote differentiation of spermatogonia
What do Sertoli cells do after stimulation by FSH?
- produce growth factors (which can encourage leydig among other cell growth) - promotes cell division to increase # of spermatogonia
- produce ABP (androgen-binding protein) which controls the bioavailability of androgens
- aromatize androgens into estrogen (necessary)
- facilitate/support spermatogenesis in the seminiferous tubules of the testes
- produce inhibin which negatively feeds back onto the anterior pituitary
- increase LH receptors on Leydig Cells
Interactions between Leydig & Sertoli Cells
- LH binds to LH receptors on Leydig cells
- signal transduction pathway leads to new protein synthesis, specifically enzymes that convert cholesterol → testosterone
- testosterone can migrate into Sertoli cells...
- FSH binds to its receptor on Sertoli cells, activates signal transduction pathway for production of new proteins: GFs that promoter LH receptor formation on the surface of Leydig cells & aromatase, which converts that testosterone provided by the Leydig cells into estradiol
What are the 2 processes of spermatogenesis?
- 1. repetitive mitosis - spermatogonia divide mitotically to produce more stem cells & a differentiated primary spermatocyte
- 2. two stages of meiosis - begin only at puberty: spermatogonia → primary = mitosis
- primary → secondary = meiosis I
- secondary → spermatids = completion of meiosis II
- 1: spermatogonia undergo mitosis to expand population
- then one of the spermatogonia that is the product of spermatogonia mitosis undergoes meiosis I to become primary (4N), then secondary (2N), & finally a haploid (1N) spermatid
2: spermatid move toward the seminal canal (center of the seminiferous tubule) & tail development begins
3: their tails continue to develop cluster as they cluster within the center of the seminal canal
4: their head changes shape to become more streamlined
5: fluid moves mature spermatozoa from the seminal canal toward the epididymus
*only in the epididymus do spermatozoa tails become mature, resulting in motile spermatocytes
Final Maturation of Sperm in Epididymus
- there is a progressive increase in sperm motility (maturation of motors & mitochondria in the mitochondrial sheath)
- the sperm acrosome matures, gains the ability to bind ovum's zona pellucida
- there is a decrease in cytoplasm & cell volume
Semen (seminal fluid)
- an organic fluid secreted by the accessory sex glands the seminal vesicles supply 60% of the fluid, which is high in fructose & prostaglandins
- products of the prostate & bulbourethral glands also make up the seminal fluid
- it contains proteolytic + other enzymes that promote the survival of spermatozoa & provide a medium through which they can move or "swim"
- its production is dependent on testosterone
When is sperm production androgen independent & when is it androgen dependent?
- it's androgen independent in early stages
- it's androgen dependent in later stages
How long does it take for spermatozoa to be produced?
- its activation allows the sperm to move forward (progressive motility)
- it's located in the “principal piece” of the sperm tail & is a Ca2+ channel protein that permits cAMP-dependent Ca2+ ion influx
What help direct sperm motility toward the ovary?
olfactory sensors in head of sperm help
How many spermatocytes does each ml of semen contain?
- ~100 million
- semen volume & sperm count decrease rapidly w/ repeated ejaculation
- sperm move at ~3 mm per minute
- it takes them 30 – 60 minutes to reach the Fallopian tubes
What temperature range is important for normal sperm production?
- temperature lower than normal body temperature (aka lower than (32o C)
- undescended testes cannot make healthy sperm & environmental causes of high testes temperature may also produce infertility or sterility
What is the sperm count of a man who is essentially sterile?
less that 20 million spermatocytes per ml semen
What are the only reliable means of male contraception?
condoms or a vasectomy
What parts of the autonomic nervous system are active during a male erection?
- an erection is accomplished by stimulation of parasympathetic nerves & inhibition of sympathetic nerves that control blood flow to the penis
- a key mediator is nitric oxide, which is released at nerve terminals & causes cGMP production in vascular smooth muscle cells → vasodilation
How does sildenafil (viagra) enhance an erection?
it inhibits cGMP breakdown, enhancing vasodilation
What is ejaculation preceded by?
- emission, the movement of semen into the proximal urethra
- emission is primarily under sympathetic control & is produced by peristaltic contractions of the vas deferens, seminal vesicles, & prostate
- there is also constriction of internal sphincter of urinary bladder
a reflex action triggered by entry of semen from the proximal urethra into the bulbous urethra
- drug taken my females to treat ovulation problems in women who want to become pregnant
- has the potential to create multiple ovulations within the same cycle
Describe the structure of sperm:
- 1) Acrosome: specialized golgi derived structure; found in the head; enzyme filled
- 2) Mid-piece: houses mitochondria to provide energy for flagellum (tail)
- 3) flagellum tail
(4N; 92; tetraploid) formed from spermatogonial stem cells dividing by mitosis; are initially diploid and are undergo meiosis
(2N; 46; diploid) primary spermatocytes that have undergone meiosis I; they undergo a meiosis II which results it HAPLOID spermatids
one primary spermatocyte produces:
- the process by which spermatids are remodeled to form mature sperm (spermatozoa)
- elongation, tail development, cytoplasm shed
What stimulates reproductive tract muscular contractions that push the sperm up the cervical canal, through the uterus, and into the fallopian tube?
prostaglandins from the SEMEN
What are four really important steps of fertilization?
- 1) capacitation
- 2) acrosome reaction
- 3) eureka moment - oozyte and sperm PMs fuse
- 4) block of polysperm (Corticol reaction)
- freshly ejaculated sperm are unable to fertilize until they undergo capacitation, a process where the glycoprotein coat and seminal proteins are removed from the acrosome surface (takes about 7 hours)
- in vivo this step typically occurs in the female reproductive tract after ejaculation
- begins with the sperm penetrating the zona pellucida of the oocyte
- ZP3 is the sperm receptor on the oocyte and when it detects sperm it initiates the reaction
- the acrosome membrane of the sperm perforates due to the action of angiotensin converting enzyme (ACE)
- the acrosome membrane fuses with the sperm membrane
- this fusion causes release of hyaluronidase and proteases from the sperm that break down and permit sperm penetration through the zona pellucida
- a glycoprotein receptor in the zona pellucida that binds sperm and initiates the acrosome reaction
- it's unique among species, thus it is the protein that determines specieality
angiotensin converting enzyme (ACE)
- enzyme derived from the acrosome that perforates the sperm's acrosome membrane
- this perforation releases enzymes that break down the matrix and allow the sperm to penetrate through the follicle and zona pellucida
cortical (zona) reaction
- oocyte cortical granule contents are released and they modify the zona pellucida through cross-linking and proteolysis, making it impenetrable to other sperm (mostly done by lysosomal enzymes from granules)
- called the block to polyspermy and it occurs within seconds to minutes of sperm penetration
In addition to the cortical (zona) reaction, what other event helps prevent polyspermy?
a calcium pulse within seconds of penetration that gets repeated across the oocyte membrane