Endocrinology of male Reproduction

Endocrine control of male reproduction

 GnRH is secreted from hypothalamus to release FSH and LH from the anterior pituitary.

 FSH acts on the seminiferous tubules of the testes and is responsible for spermatogenesis
i.e., from the initial division of the spermatogonia through the formation of secondary
spermatocytes. Thereafter the testosterone is responsible for sperm cell development.

 LH stimulates the growth and development of interstitial cells or Leydig cells in between
the seminiferous tubules of the testes and the secretion of the testosterone and androgens
from these cells.

 These androgens are secreted into the blood stream where they cause the development of
the secondary sexual characteristics in the male and development and maintenance of
male reproductive tract. The androgens suppress GnRH, LH, FSH secretion by a negative
feedback on the pituitary and hypothalamus.

 FSH also interacts with receptors on sertoli cells to cause production of androgen binding
protein (ABP), conversion of testosterone to dihydrotestosterone and estrogen,
completion of sperm release (spermiation) and secretion of inhibin. The inhibin secreted
into the blood stream has a negative feedback effect on FSH but not on LH secretion.

 The ABP forms a complex with androgens and is carried along with the spermatozoa into
the epididymis.

 Although much of the testosterone secreted into the seminiferous tubules is converted
into dihydrotestosterone (DHT) by the enzyme 5 alpha reductase, some of the
testosterone gets converted to estrogens by the enzyme aromatase.

Functions of Testosterone

 Sexual differentiation of external male genetalia and descent of the testes into scrotum in
fetuses or neonates.
 Keratinization of the preputial epithelium, separation of glans penis from prepuce, growth of
the penis and prepuce at puberty.
 Growth and maintenance of accessory sex glands.
 Sexual desire or libido, ability for normal erection and ejaculation.
 Secondary sexual characteristics like hair or horn growth, male attitudes, voice, increased
bone thickness, increased muscle tissue with different distribution of fat from female.
 Maintenance of secretory and absorptive activities and structure of efferent ducts, epididymis
and ductus deferens including ampulla.
 Spermiogenesis – development and maturation of spermatids and spermatozoa.
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 Spermatogenesis

Spermatogenesis is a complex process of cell division and differentiation resulting in the

formation of spermatozoa.
Spermatozoa are formed in the seminiferous tubules of the testes, by a series of cell divisions
followed by a metamorphosis, produces a highly differentiated and potentially motile cell, the
spermatozoa.

Spermatogenesis can be divided into two phases

 Spermatocytogenesis
 Spermiogenesis.

Spermatocytogenesis:

 Spermatocytogenesis is the proliferative stage in which primitive germ cells are

multiplied by a series of mitotic divisions followed by the meiotic divisions which
produce the haploid stage spermatid.
 Spermatocytogenesis begins with the mitotic division of spermatogonia on the basement
membrane of seminiferous tubules and proceed towards the lumen.
 Primordial germ cells migrate from inner lining of yolk sac to the undifferentiated
gonads.
 These primordial germ cells divide several times to form gonocyte.
 The gonocyte undergo mitosis during fetal and prepubertal life and differentiate into
spermatogonia, thereafter their developments remain arrested until onset of puberty.
 There are many type of A spermatogonia like A0, A1, A2, A3 and A4 which depends on
species.
 Spermatogonia are activated to form active type A spermatogonia. The type A1
spermatogonia divide mitotically and form type A2, A3 and A4 spermatogonia.
 The type A4 divide mitotically again and form intermediate spermatogonia.
 The intermediate spermatogonia divide mitotically and form type B spermatogonia.
 The type B spermatogonia undergo last mitotic division and form primary spermatocyte.
 An active spermatogonium undergoes four mitotic division in bull & rams and form 16
primary spermatocytes.
 Each primary spermatocytes undergoes first meiotic division and form two secondary
spermatocytes which contain haploid number of chromosome.
 Each secondary spermatocytes undergoes second meiotic division and form two rounded
spermatids.
 From each primary spermatocytes four spermatids are formed. Thus from one active
spermatogonia 64 spermatids are formed in bull and rams.

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Spermiogenesis:

Spermiogenesis is the differentiative phase in which the nucleus and cytoplasm of spermatid
undergo morphologic changes to form the sperm cells. Metamorphosis of spermatid into
spermatozoa, is called as spermiogenesis. Spermiogenesis consists of four phases namely
 Golgi phase
 Cap phase
 Acrosomal phase
 Maturational phase

Golgi phase (Formation of acrosomal vesicle)

The newly formed spermatid has a well-developed golgi apparatus. Small vesicles of the golgi
fuse, giving rise to larger secretory granules called proacrosomic granules. Vesicle fusion
continues until a large acrosomic vesicle is formed that contains a dense acrosomic granule.
During the last half of the golgi phase the centrioles migrate to a position opposite to the
acrosomic vesicle Proximal centriole gives rise to the attachment point for the tail. Distal
centriole will give rise to the developing axoneme inside the cytoplasm of the spermatid.

Cap phase (Formation of acrosomal cap)

The acrosomic vesicle flattens and begins to form a distinct cap consisting of an outer acrosomal
membrane and inner acrosomal membrane. The golgi migrates towards the caudal part of the
cell. Distal centriole form the axoneme or flagellum which projects away from the nucleus
toward the lumen of the seminiferous tubule.

Acrosomal phase (Elongation of nucleus and cytoplasm)

Spermatid nucleus begins to elongate. Acrosome covers the majority of the anterior nucleus. A
unique system of microtubules known as manchette extends from posterior nucleus. Portions of
manchette attach to the region of the nucleus just posterior to the acrosome. Some of the
microtubules of the manchette will become the post nuclear cap. Formation of annulus which
will form junction between the middle piece and principal piece in future. Mitochondria begins
to concentrate near axoneme.

Maturation phase

Manchette migrate towards the tail and begin to disappear. Mitochondria are assembled around
flagellum to form the middle piece. Dense outer fibres form around the flagellum. Post-nuclear
cap is formed from manchette microtubules. Annulus forms the juncture between the middle
piece and principal piece. During later stages of spermiogenesis, sertoli cells forms the
cytoplasm remaining after elongation of spermatid into a spheroidal lobule called residual body.
Formation of residual bodies completes final maturation and spermatids are ready for release.

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Duration of spermatogenesis

Duration of spermatogenesis different species

Species Duration of one cycle Number of cycles Duration of complete

(Days) required to complete spermatogenesis
spermatogenesis
Boar 9 4.3 37
Ram 10 4.7 47
Horse 12 4.5 54
Bull & Dog 14 4.3 60
Buffalo 8.6 4.4 38

Spermatogenic cycle and wave

If one closely examine serial cross section of a seminiferous tubule, each section has one group
of cells. Each group has been classified as stage. These stages change in each cross section of
the tubule with time. These stages change not only with time but also along the length of
seminiferous tubule. A spermatogenic cycle is defined as the time required for the reappearance
of the same stage within a given cross section of the tubule. Nearly 4-5 cycle are required before
A-type spermatogonia change to full spermatocyte.

The distance between two similar cellular associations in the seminiferous epithelium is called
spermatogenic wave. Spermatogenic wave is approximately 10 mm long in bull. Thus the site of
spermiation (stage 12) along the seminiferous tubule is constantly changing, creating a wave of
sperm release down the length of the tubules. Sometimes certain irregularities or breaks are
noted. These breaks in the sequences are called modulation.

Spermiation

Release of formed germ cells into lumen of the seminiferous tubules is known as spermiation.

Factors affecting spermatogenesis

1. Physical factors
2. Chemical factors
3. Nutritional factors
4. Hormonal factors
5. Genetic factors
6. Pathological factors
7. Age factors

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1. Physical factors

Irradiation: Irradiation produces interference with spermatogenesis by injuring

spermatogonia, spermatocytes and spermatids.The spermatocytes are most sensitive to
irradiation while leydig and sertoli cells are quit resistant. Steroidogenesis is not affected
much by the X-rays.

Hyperthermia: High ambient temperature will cause testicular degeneration which

affects the spermatogenesis.

Hypothermia: Spermatogenesis seems to be more resistant to cooling than to heat and

the tunica dartos and cremaster muscle contract to protect the testes from the effects of
cold.

Light: The influence of light on control of spermatogenesis is brought through the

capacity of it to control the pituitary gonadotrophin. The pineal body operated as a
neuroendocrine transducer mediating light effects on the testes.

Low oxygen tension: Spermatogenesis is severely impaired when adopted males are
subjected to low oxygen tension at high attitude or in experimental chambers.

2. Chemical factors

Antispermatogenic drugs like Cadmium, Alkylating agents, Diamines, Nitrogen-

containing compounds etc, organochlorine derivatives and organophosphates: eg.
Dichlorovos and carbamates affects the spermatogenesis.

3. Nutritional factors:

Low plane of nutrition: The low plane of nutrition or malnutrition cause a greater stress
on pre-pubertal animals than in post- pubertal animals. It causes hypoplasia of the testes
and accessory sex glands and delays puberty. Adversely affect gonadotropins secretion
i.e FSH and LH and thereby reduces the spermatogenic activity.

High plane of nutrition: High plane of nutrition is frequently cited as a cause of

infertility especially in fatty, overfed and obese animals. It indicated that excessively fatty
bulls may have enough fat around the testes in the scrotum, affecting the
spermatogenesis.

Vitamins deficiencies: Germinal and leydig cells are affected by hypovitaminosis A.

Vitamin A is epitheliotrophic and the severe deficiency produce degeneration of
seminiferous tubule and interfere with spermatogeneis. 4. Hormonal factors

Exogenous steroids: Exogenous steroids affect testicular function by altering the

secretion of gonadotropins.

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 Pituitary factors: Reduced spermatogenesis with testicular atrophy may be caused by
failure of FSH and LH. Many stress factors affect LH and FSH release, the most
important being inanition due to low plane of nutrition. Tumors of the pituitary gland also
cause atrophy of the pituitary gland and failure of gonadotropic production.

5. Genetic factors:

Heredity, Inbreeding, Cytogenetic disturbances, hybridization, Freemartinism.

6. Pathological factors

Congenital factors: Testicular hypoplasia, cryptorchidism,imperfect descent of the

testes, scrotal or inguinal hernia affect the spermatogenesis.

Acquired factors: Testicular degeneration, testicular fibrosis

7. Age factor

Degenerative changes in seminiferous tubules, focal degeneration and calcification of

tubules have been noticed in aging. A decline in germinal tissue, an arrest of the later
stages of spermatogenesis and increase in connective tissue are associated with aging.

Morphology of spermatozoon

The male gamete produced by spermatogenesis in the seminiferous tubule of the testis is
called spermatozoon. The mature spermatozoon consists of mainly three parts: the head,
neck and the tail. The tail consists of the middle piece, the principal piece & the end
piece.

1.Sperm Head: The shape of sperm head in bull, boar & rabbit is ovoid and elongated
shape in fowl. The sperm head has mainly three components: nucleus, acrosome & post
nuclear cap.

Nucleus: It is composed of densely packed chromatin. The nucleus contains only half of
the amount of DNA present in somatic cells of the same species

Acrosome: It is a doubled-layered membranous sac. It is formed from Golgi complex

which covers about two third of the anterior part of the sperm nucleus. The outer
membrane is called outer acrosomal membrane and the inner membrane is called inner
acrosomal membrane. In between the two membranes, acrosomal content remain
present. The acrosomal content contains various hydrolytic enzymes like lysosome which
are required for penetration of the ovum.

Post nuclear cap: The posterior 1/3rd of the nucleus from the equatorial zone to the base
of sperm cell is covered by a sheath called postnuclear cap or nuclear sheath or post
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acrosomal sheath. It is made up of fibrous protein rich in sulphur. After death of sperm
cell, the permeability of the postnuclear cap increases and allow entry of stain. That is
why post nuclear cap takes more deep stain of eosin than anterior part of nucleus.

2.Neck or connecting piece: The neck is the structure which connects the head with
mid-piece. It may be divided into parts; the capitulum and the segmented columns. The
capitulum fits into the implanted socket, a depression into the posterior nucleus.

3.Tail: The tail consists of the middle piece, the principal piece & the end piece.

Middle piece: The portion of the tail between the neck and the annulus is middle piece. It
consist of the axoneme, outer dense fibres and the mitochondrial sheath. The axoneme is
composed of nine pairs of microtubules that are arranged radially around two central
filaments i.e. ‘‘ 9+2’’ arrangement of microtubules that extends the full length of the tail.
It originates from the distal centrioles and forms the central core of entire lengths of the
tail. Another set of 9 fibres called outer dense fibres or course fibres which surround the
axoneme and thus axoneme and outer dense fibres form a ‘‘ 9+(9+2)’’ arrangement
throughout the length of the middle piece and principal piece. The mitochondria remain
arranged in a helical pattern around the outer dense fibres and form mitochondrial sheath.
The mitochondrial sheath is source of energy needed for sperm motility.

Annulus or jensen’s ring: It demarcates the junction between the middle piece and the
principal piece.

Principal piece: It is the longest part of the spermatozoon. It consists of axoneme as a

central core, which is surrounded by outer dense fibres. The outer dense fibres are
surrounded by a fibrous sheath (in place of mitochondrial sheath in middle piece).

End piece: The junction between the principal piece and the end piece is clearly
demarcated by the termination of the fibrous sheath. The end piece contains only
axonema. The whole structure of sperm is covered by a plasma membrane.

(Middle piece= Axonema + Outer dense fibres+ Mitochondrial sheath

Principal piece= Axonema + course fibres+ fibrous sheath

End piece= Axoneme)

Length of spermatozoon (μm) in different species

Species Cow bull Buffalo bull Ram Boar Stallion Man

Total length 69.3 62.0 62.6 48.5 59 55