Male Reproductive

The primary organs in the male reproductive

system are the testes; have dual functions

produces sperm (spermatogenesis)

produces androgens (steroidogenesis)

the reproductive ducts which carry sperm from

the testes to the exterior of the body; these are

epididymis

ductus deferens

ejaculatory duct

urethra

accessory glands which produce secretions that

combine with sperm to create semen; these are

seminal vesicles

prostate gland

bulbourethral/Cowper’s glands

The male genitalia (external sex organs) are the

scrotum and penis

Testis

The male gonad or reproductive gland

contained in scrotum

Each testis measures about 3.8 cm long and 2.5

cm wide

surrounded by 3 tunics

tunica vaginalis-

the serous covering of the testis

derived from peritoneum

consists of a visceral and a parietal lamina

tunica albuginea-

the fibrous covering of the testis

extensions divide testis into 250-300

compartments called lobules

tunica vasculosa-

the vascular layer of the testis

consists of a plexus of blood vessels

clothes the inner surface of the tunica

albuginea

Lobules

each lobule contains 1 to 4 seminiferous

tubules, where sperm are produced

each tubule averages about 80 cm in length and

forms a loop

seminiferous tubules in a lobule join to form

tubulus rectus, which carries sperm into the rete

testis, a reticular network of tubules

from there, efferent ductules carry sperm out of

the testis into the epididymis,

the testis and epididymis are supplied by the

testicular artery and their veins drain into the

pampiniform plexus, which forms the bulk of the

spermatic cord

lymphatics accompany the testicular vessels

and drain into the lumbar (aortic) nodes

in between the seminiferous tubules are the

Leydig cells

Seminiferous Tubules

contains

germ cells at various stages of development

Sertoli/sustentacular cells

Sertoli cells extend from the basement

membrane of the seminiferous tubules to reach

the lumen

Sertoli cells are in constant contact with lots of

spermatogenic cells, and they send cytoplasmic

processes to surround those cells

tight junctions between adjacent Sertoli cells

near the base of the seminiferous epithelium

constitute the blood-testis barrier (BTB), a

structure that partitions seminiferous tubules

into a basal and an adluminal compartments

Leydig cells

found in interstitial supporting tissue between

the seminiferous tubules

they are almost non-existent prior to the onset

of testicular testosterone production at puberty

they produce testosterone

Spermatogenesis

The development of male gametes (spermatozoa) from spermatogonia

begins at puberty and continues throughout life

occurs in the seminiferous tubules

takes about 74 days

has three phases

proliferative/mitotic phase

meiotic phase

spermiogenic phase

Proliferative Phase

Type A spermatogonia (stem cells) which lie on

the basal lamina of the seminiferous tubules

undergo mitosis to produce more type A

spermatogonia to renew their stock and type B

spermatogonia

the type B spermatogonia undergo further

mitotic division to form primary spermatocytes

Meiotic Phase

each primary spermatocyte undergoes the first

meiosis to form two secondary spermatocytes,

each containing a haploid number of

chromosomes

spermatogonia do not separate completely after

meiosis due to incomplete cytokinesis and

remain joined by intercellular bridges

intercellular bridges are thought to facilitate

biochemical interactions allowing synchrony of

germ cell maturation

each secondary spermatocyte undergoes a

second meiosis to form two round spermatids

Spermiogenic Phase

the process that converts spermatids into mature

sperm (spermatozoa)

it has four stages, these are:

the Golgi phase

the cap phase

acrosome phase

maturation phase

as each division takes place, the daughter cell

migrates closer to the lumen of the seminiferous

tubule, so that spermatids are immediately

adjacent to the lumen

the release of sperm into the lumen of the

seminiferous tubules is called spermiation; the

remaining unnecessary cytoplasm and

organelles are removed during spermiation

Spermatozoon

It consists of:

Head

Midpiece

Tail

Head

The head contains the condensed nucleus which is capped by an apical vesicle (acrosome) filled with hydrolytic enzymes

The acrosome plays an important role in fertilization

Midpiece

it contains large helical mitochondria that generate the energy for swimming

Tail

contains microtubules and propels the sperm during motility

Factors Regulating Spermatogenesis

Hormonal Control of Spermatogenesis Endocrine factors secreted by the hypothalamus, pituitary gland and local regulators of testis function, as well as modulators of gene expression in the pituitary gland are involved in the regulation of spermatogenesis

both Sertoli cells (SC) and Leydig cells (LC)

regulate spermatogenesis by steroidogenesis

and growth factors production

SC stimulated by FSH produce inhibin (In),

activin (Ac) and androgen binding protein (ABP)

inhibin has negative feedback control on

pituitary and FSH secretion

inhibin also binds to Leydig cells (LC) regulating

testosterone (T) production

activin enhances FSH production

activin binds to round spermatids and

spermatogonia (SP), effecting spermatogenesis

activin also blocks testosterone synthesis in the

Leydig cells

ABP is essential to concentrating testosterone in

levels high enough to initiate and maintain

spermatogenesis, which can be 20-50 times

higher than the concentration found in blood

FSH and LH are known to influence germ cell

fate. They suppress apoptosis of germ cells

Leydig cells also produce epidermal growth

factors (EGF) which bind to spermatogonia and

spermatids regulating cell divisions

considerable amounts of the testosterone are

metabolized to estrogens by the enzyme

aromatase in Sertoli cells

this reaction is blocked by inhibin

FSH is required for the initiation of

spermatogenesis

once spermatogenesis is initiated, FSH is no

longer required; testosterone alone will maintain

active spermatogenesis

Temperature

The testes are located in a sac called the scrotum

which holds the testes away from the body since normal body temperature is too warm for sperm production

Scrotal temperature is maintained by:

the counter current heat exchanger formed by

the close association between the testicular

artery and the pampiniform plexus of veins

surrounding the vas deferens which cools the

arterial blood before entering the testicular

epithelium

testicular altitude (relative to the abdomen)

regulated by cremaster muscle which lowers or

raises testes within scrotal sac to cool or warm

the testes respectively

regulation of scrotal skin area by the dartos

muscle (smooth muscle) within the dermis of the

scrotum: increase (relaxed dartus muscle) or

decrease (contracted) surface area for heat

exchange

the scrotum is well supplied with sweat glands

which presumably aid in cooling the testes

these features maintain a testes temperature

about 3o C below the body temperature

Other Factors

Dietary deficiencies (such as vitamins B, E and

A)

anabolic steroids

metals (cadmium and lead)

x-ray exposure

dioxin

alcohol

infectious diseases

will also adversely affect the rate of spermatogenesis

Sperm Maturation and storage

Sperm from the seminiferous tubule enter the

epididymis via other ducts

the sperm are stored in the epididymis for up to

2 weeks where they mature and develop motility

as sperm transit the epididymis, they are bathed

in a specialized fluid rich in proteins, ions, and a

number of other molecules

complex interactions between spermatozoa and

epididymal fluid contribute to sperm maturation

sperm is stored in the vas deferens until

ejaculation

Sperm Capacitation

Freshly ejaculated sperm are unable or poorly

able to fertilize eggs

they must first undergo a series of changes that

give them the ability to fertilize

the acquisition of the ability to fertilize is known

as capacitation

capacitation occurs while sperm reside in the

female reproductive tract for a period of time

it is stimulated by secretions in the vagina,

uterus, and uterine tubes

it takes between 5-7 hours

it is associated with

removal of adherent seminal plasma

proteins

reorganization of plasma membrane lipids

and proteins

an influx of extracellular calcium ions

increase in cyclic AMP

decrease in intracellular pH

capacitated sperm

display hyperactivated motility

undergo the acrosome reaction

Semen

The grayish white bodily fluid ejaculated at the

time of orgasm

it contains sperm (2-3%) and secretions from

the

testis

epididymis (<5%)

seminal vesicles

prostate gland

bulbourethral glands or Cowper’s glands

the initial secretion is from the bulbourethral or

Cowper’s glands (<5%)

it is secreted just before emission of semen

it is thought to serve as a lubricant(?) for inserting the penis into the vagina

provide the mucus which provides a jelly like consistency to the semen and is important for the mobility of the sperm in the cervix and the vagina

next is the secretion from the prostate (30%)

prostatic secretion contains: citric acid, prostate-specific antigen, acid phosphatase, zinc, and proteolytic enzymes

the zinc content in the prostatic secretions is vital for stabilizing chromatin which contains the DNA in the sperms. Deficiency of zinc

can lead to lower fertility as it can render the

sperms fragile.

it is alkaline

it neutralizes any residual urine, which tends

to be acidic, and the acidity of the vaginal

secretions

liquefies coagulated semen into a viscous

fluid

the terminal portion is from the seminal vesicles

this is about 60% of total semen volume

contains:

mucus

amino acids

fructose as the main energy source for the

sperm

prostaglandins to stimulate female uterine

contractions to move the semen up into

the uterus

normal semen volume is between 1.5-5.0 ml

the pH is 7.0-8.3

a count of 15 million and above spermatozoa/ml

is considered the normal range

counts below 15 million/ml are considered low

Transport

Testosterone circulates in blood at concentrations above its aqueous solubility by binding to circulating plasma proteins

about 65% binds avidly to sex-hormone binding

globulin (SHBG)

about 33% is bound to lower-affinity, high

capacity binding sites (albumin, ⍺1-acid

glycoprotein, transcortin)

1-2% remaining non-protein bound

the “free” (non-protein bound) fraction is the

most biologically active with the loosely protein-

bound testosterone constituting a larger

“bioavailable” fraction of circulating testosterone

circulating testosterone levels demonstrate

distinct circhoral and diurnal rhythms

testosterone is secreted at adult levels during 3

epochs of male life:

transiently during the first trimester of

intrauterine life

during neonatal life

after puberty to maintain virilization

testosterone undergoes metabolism to both

bioactive metabolites and to inactivated oxidized

and conjugated metabolites for urinary and/or

biliary excretion

Action

testosterone has both androgenic and anabolic

effects

its action is initiated by the binding of

testosterone or its analogs to the androgen

receptor causing its activation

in addition, testosterone is also converted to its

bioactive metabolites, dihydrotestosterone

(DHT) and estradiol

in the majority of target cells, some testosterone

is converted into DHT by the enzyme 5-α

reductase

DHT has higher binding affinity to the androgen

receptor and 3-10-fold greater molar potency

than testosterone

DHT cannot be aromatized to estrogen, and

thus its effects are purely androgenic

testosterone and DHT do bind to the same

intracytoplasmic androgen receptor

the androgen-receptor complex binds to DNA

this results in mRNA syntheses, and

subsequently in syntheses of cytoplasmic

proteins, which lead to cell growth and other

secondary effects mediated by androgens

congenital 5-α reductase deficiency individuals

may have normal male external genitalia, often

with an unusually small penis (micropenis) and

the urethra opening on the underside of the

penis (hypospadias), ambiguous genitalia, or

normal female genitalia

these individuals have male internal genitalia

but usually have female primary sex

characteristics and may be raised as females

high concentrations of testosterone at puberty

leads to marked virilization including phallic

growth and, occasionally, masculine gender

reorientation although prostatic development

remains rudimentary