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Isfahan University of Technology
Isfahan, Iran
Advanced
Reproductive Physiology
(part 1)
By: A. Riasi
(PhD in Animal Nutrition & Physiology)
http://riasi.iut.ac.ir
The topics
• Puberty and sexual maturity
• Physiology of gamete production
• Hormonal & non-hormonal secretions of
reproductive in male and female animals
• Physiology
development
of
pregnancy
and
embryo
The topics (continue)
• Physiology of parturition
• Pheromones
• Abnormality of reproduction
• Reproductive immunology
• Recent advance associated with reproductive
physiology
References

Pathways to Pregnancy and Parturition, P.L. Senger, Second
edition, 2011.

Reproductive in Farm Animals, By: E.S.E. Hafez, 2000.

Improving the Reproductive Management of Dairy Cattle
Subjected to Artificial Insemination, By: IAEA-TECDOC1533, 2007.

Review and Original Papers
Puberty and sexual maturity

What is the difference between puberty and
sexual maturity?
Puberty and sexual maturity

Definition of puberty in females:

Age at first estrus

Age at first ovulation

Age at which a female can support pregnancy
without deleterious effects.
Puberty and sexual maturity

Definition of puberty in males:

Age when behavioral traits are expressed.

Age at first ejaculation.

Age when spermatozoa first appear in the ejaculate.

Age when spermatozoa first appear in the urine.

Age when the ejaculate contains a threshold number
of spermatozoa.
Puberty and sexual maturity

Hypothalamus control puberty in animals

Two centers in hypothalamus:
 Tonic
center
 Surge
center
Puberty
Surge
Surge
Tonic
Tonic
Puberty
 In
near to puberty age:
 Sensitivity of the hypothalamic tonic center
 GnRH and gonadotrophins secretion
 Sensitivity of GnRH surge center in hypothalamus
Puberty
Puberty
Effect of testosterone on male brain
T
T
E2
Surge Center
Does not
Develop
Testis
Blood Brain
Barrier
Effect of estrogen on female brain
aFP + E2
E2
Placenta
E2
E2
Ovary
Blood Brain
Barrier
Surge Center
Develops
E2
Factors affecting puberty

Puberty may affected by different factors:
 Heritability
 Environmental
 Birth
month
 Social
condition
 Nutritional
 Age
factors
factors
and weight
Role of leptin in puberty

Effect of a minimum percentage of body fat

Serum leptin concentrations

Leptin does not serve as triggering signal

Leptin acts mainly as a permissive signal that
permits puberty to occur
Role of leptin on puberty
Functional and organization of testis

The testes have two compartments:
 Tubular
compartment (tubuli seminiferi)
 Interstitial
compartment (interstitum)
Functional and organization of testis

The interstitial compartment:

The leydig cells

Secretion of testicular testosterone

Secretion of insulin like factor 3 (INSL3)

Immune cells

Blood and lymph vessels

Nerves

Fibroblasts
Functional and organization of testis

Different type of leydig cells:

Stem Leydig cells as founder cell

Progenitor Leydig cells as a committed stem cell

Fetal Leydig cells as a terminally differentiated cell
in the fetus

Adult Leydig cells as the terminally differentiated
Leydig cell
Functional and organization of testis

The interstitial compartment also contains cells
belonging to the immune system:
 Macrophages,
probably influence the function of
leydig cells:

Proliferation

Differentiation

Steroid production
 Lymphocytes
Functional and organization of testis
Immunological compartments of the testis. Sertoli
cells (S) traverse the testicular tubules, keeping in close
contact with the germ cells. Together with the peritubular
cells, they form the seminiferous epithelium. The blood–
testis barrier (tight junctions) is built by tight junctions
between neighboring S, dividing the seminiferous tubules
into a basal and adluminal compartment. The interstitial
space contains the Leydig cells (L) and the immune cells
such as macrophages (MP), dendritic cells (D), mast cells
(M), and T cells as well as blood vessels (BV) with
migrating leukocytes
Functional and organization of testis

Spermatogenesis takes place in the tubular
compartment:
 Germ
cells
 Somatic
cells

The peritubular cells

Sertoli cells
Functional and organization of testis

Peritubular cells produce several factors that are
involved in cellular contractility (Holstein et al.
1996):
 Panactin
 Desmin
 Gelsolin
 Smooth
muscle myosin and actin
Functional and organization of testis

Several regulators of cell contractions are
reported:
 Oxytocin
and Oxytocin-like substances
 Prostaglandins
 Androgenic
steroids
 Endothelins
 Endothelin
converting enzymes
 Endothelin
receptors
Functional and organization of testis
 These cells secrete extracellular matrix and
factors typically expressed by connective tissue:
 Collagen
 Laminin
 Vimentin
 Fibronectin
 Growth
factors
 Fibroblast
Functional and organization of testis

Sertoli cells synthesize and secrete a large
variety of factors:
 Proteins
 Cytokines
 Growth
factors
 Opioids
 Steroids
 Prostaglandins
 Modulators
of cell division
Functional and organization of testis

The Cytoplasm of sertoli cells contains:
 Eendoplasmic

Smooth type

Rough type
A
reticulum
Prominent Golgi apparatus
 Lysosomal
granules
 Microtubuli
and intermediate filaments
Functional and organization of testis

Another important functions of Sertoli cells:
 Final
testicular volume
 Sperm
production
Functional and organization of testis
Hormonal control of testicular function

Pituitary gonadotropes are the central structure
controlling gonadal function.

In turn, are regulated by the hypothalamic
gonadotropin-releasing hormone (GnRH).

GnRH secretion depends on the activation of
the GPR54 receptor.
Hormonal control of testicular function

GnRH receptors are located on the surface of
the GnRH neurons and stimulated by the
peptide kisspeptin.

The pituitary function is also under the control
of gonadal steroids and peptides that influence
its activity both directly and through the
hypothalamus.
Hormonal control of testicular function

The Gonadotropin-producing cells constitute
approximately 15% of the adenohypophyseal
cell.

The same cell type is believed to secrete both
gonadotropins.

Pituitary gonadotropes are often found in close
connection with prolactin cells.
Hormonal control of testicular function

Dramatic changes by pubertal activation:
 The
proximity of several stimulated endocrine cells
types to each other and to the germinal cell line.
 Central
feedback actions:

FSH

LH

Testosterone
Hormonal control of testicular function

In male
testosterone is major the hormone
controlling GnRH secretion

Testosterone
can
act
as
such
metabolism to DHT or estradiol.
or
after
Hormonal control of spermatogenesis

During spermatogenesis gonadotropes regulate
testicular function.

Testosterone and FSH affect the seminiferous
tubules and enhance spermatogenesis

LH affect the release of sperm from germinal
epithelium (spermiation)
Hormonal control of testicular function

High concentration of testosterone may find in
seminiferous tubules, rete testis, afferent
tubules and epydidymis.

Effect of inhibin and activin on FSH secretion
and spermatogenesis
Hormonal control of testicular function

Other hormones may affect testicular function:
 Prolactin
 GH
and IGF-I
 Insulin
 Glucocorticoids
 Thyroid
hormones
 Aldosterone
 PGE2
 Testicular
GnRH
Testicular androgens

Androgens are essential for:
 The
development and function of testes
 Maturation
of secondary sexual characteristics
 Masculinization
of the bone-muscle apparatus
 Libido
 Stimulation
of spermatogenesis
Testicular androgens

Physiological effects of androgens depend on:
 Number
of androgen molecules
 Distribution
of androgens and their metabolites
inside the cell
 Interaction
with the receptors
 Polyglutamine
number of the amino acid sequence
in the androgen receptor
 Receptor
activation
Testicular androgens

In turn, androgen concentrations in the blood
depend on:
 The
synthesis rate
 Balanced
by metabolic conversion and excretion.
Testicular androgens

Leydig cells are the main site of androgen
production.

Leydig cells cannot store androgens, de novo
biosynthesis takes place continuously.

LH as the central regulatory factor controls
both
steroidogenesis
and
cholesterol homeostasis in vivo.
Leydig
cell
Testicular androgens
Testicular androgens

Cholesterol is stored in cytoplasmic lipid
droplets.

The number of lipid droplets is inversely
related to the rate of androgen synthesis in the
Leydig cell.
Testicular androgens

Testosterone moves from the leydig cells into:
 Blood
vessel
 Lymphatic
vessel
 Seminiferous
tubules
Testicular androgens

Testosterone also give rise to two other potent
androgens:
 Dihydrotestosterone
 5α-androstandiol
(DHT)
Testicular androgens
Testicular androgens

Circulating testosterone is found in three
forms
 Free
 Bounded
with a liver-drived sex steroid-binding
globulin (SSBG)
 Bounded
with albumin and other proteins
Testicular androgens

Testosterone is excreted by urine:
 As
glucronide (1% of daily production of
testosterone)
 17-ketosteroids
products
Testicular androgens
Testosterone (T) is synthesized in the testis. After entering the target cells (in the hypothalamus, pituitary, testis and wolffian duct)
T is directly bound to the androgen receptor (AR) and the complex T-AR binds to specific DNA sequences and regulates gene
transcription, which can result different works.
Testicular androgens
Specific actions of Dihydrotestosterone (DHT). After entering the T to target cells (in the urogenital
sinus, urogenital tubercle, and several additional androgen target tissues) T is metablized to 5αDihydrotestosterone (DHT) by the enzyme 5α-Reductase type 2. DHT binds directly to the androgen
receptor (AR) and the complex DHT-AR interacts to specific DNA sequences and regulates gene
transcription, which can result in differentiation and development of the prostate, the external genitalia
and at puberty in several secondary male characteristics.
Testicular androgens
Testicular androgens

The major role of testosterone:
 Stimulates
of differentiation of the wolffian ducts
into the epididymis, vas deferens and seminal
vesicles.
 With
or without DHT causes enlargement of the
penis and seminal vesicles.
 Causes
enlargement of the larynx and thickening
of the vocal cords.
Testicular androgens

The major role of testosterone:
 Local
hormone
required
for
initiation
and
maintenance of spermatogenesis.
 Cessation
of linear growth by closure of the
epiphyseal growth center.
 Enlargement
 Important
of the muscle mass during puberty.
effect on lipid metabolism.
Testicular androgens
 The major role of testosterone:
 Initiation
of sexual drive.
 Suppression
of mammary gland growth.
 Stimulation
hematopoiesis.
 Stimulation
of renal sodium reabsorption.
 Stimulation
of aggressive behavior
 Suppression
of hepatic synthesis of SSBG, cortisol-
binding globulin and thyroxin-binding globulin.
Testicular androgens

The major role of DHT and 5α-androstandiol:
 DHT

is specifically required in the fetus
Differentiation of the genital tubercle, genital swellings,
genital folds and urogenital sinus into penis, scrotum, penile
urethra and prostate respectively.
 DHT
is required during puberty for growth of scrotum
and prostate and stimulation of prostatic secretion.
Testicular androgens

The major role of DHT and 5α-androstandiol:
 DHT
and 5α-androstandiol stimulate the hair
follicles.
 DHT
and 5α-androstandiol increase production of
sebum.
 DHT
influence the spermatogenesis.
Semen properties

Semen volume is controlled by different
factors:
 Animal
species
 Breed
 Individual
properties
 Season
of year
 Semen
collection time
Semen properties

Special proteins in semen liquid:
 Androgen
 Acrosin
binding protein (ABP)
inhibitor protein
 Glycoproteins
Semen properties

Some importatnt components in semen liquid:
 Hormones
 Vitamins
 Lipids
and fatty acids
 Immunoglobulin
 Energy
sources
A
Semen properties

Energy metabolism in sperm:
 Fructose
production by sorbitol dehydrogenase
 Fructolysis
 Role
of membrane Plasmalogens
Semen properties

Factors may affect sperm metabolism rate:
 Temperature
 pH
 Osmotic
 Sperm
pressure
concentration
 Hormones
 Gases
 Light
Some research papers associated to this lecture
1. Asadpour, R. et al. The effect of antioxidant supplementation in semen extenders on semen quality and lipid
peroxidation of chilled bull spermatozoa. Iranian Journal of Veterinary Research, Shiraz University, 2012, 13: No. 3, Ser.
No. 40.
2. Umut Tasdemir. et al. Effects of various cryoprotectants on bull sperm quality, DNA integrity and oxidative stress
parameters. Cryobiology, 2013, 66: 38-42.
3. Gaffari Tu¨rk. et al. Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density,
antioxidant activity and testosterone level in male rats. Clinical Nutrition, 2008, 27: 289-296.
4. Baghshahi et al. Antioxidant effects of clove bud (Syzygium aromaticum) extract used with different extenders on ram
spermatozoa during cryopreservation. . Cryobiology, 2014, 69: 482- 487.