Isfahan University of Technology

College of Agriculture, Department of Animal Science

Advanced Reproduction

Physiology

(Lecture 1)

Prepared by: A. Riasi http://riasi.iut.ac.ir

The syllabuses

 Puberty and sexual maturity

 Physiology of gamete production

 Hormonal & non-hormonal secretions of reproductive in male and female animals

 Physiology of pregnancy and embryo development

The syllabuses

 Physiology of parturition

 Pheromones

 Abnormality of reproduction

 Reproductive immunology

 Recent advance associated with reproductive physiology

References

1.

Reproductive in Farm Animals, By: E.S.E. Hafez

2.

Reproduction in Dairy Cattle 1&2, By: Gietema

3.

Improving the Reproductive Management of Dairy

Cattle Subjected to Artificial Insemination, By: IAEA-

TECDOC-1533

4.

Review and Original Papers

Puberty and sexual maturity

Puberty is originated from Latin word “ pubscere

 Hypothalamus control puberty in animals

 Two centers in hypothalamus:

 Tonic center

 Surge center

Puberty

Surge

Tonic

Surge

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

E

2

T

Testis

Surge Center

Does not

Develop

Blood Brain

Barrier

Effect of estrogen on female brain a

FP + E

2

E

2

Placenta

E

2

E

2 E

2

Ovary

Blood Brain

Barrier

Surge Center

Develops

Factors affecting puberty

 Puberty may affected by different factors:

 Heritability

 Environmental factors

 Birth month

 Social condition

 Nutritional factors

 Age 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 but acts mainly as a permissive signal that permits puberty to occur.

Role of leptin on puberty

Physiology of Testicular Function

Functional organization of testis

 The testes have two compartments:

 Tubular compartment ( tubuli seminiferi )

 Interstitial compartment (interstitum)

Functional 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

 Loose connective tissue

Functional organization of testis

 Different type of leydig cells (Ge and Hardy, 2007):

 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 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 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 organization of testis

 Spermatogenesis takes place in the tubular compartment:

 Germ cells

 Somatic cells

 The peritubular cells

 Sertoli cells

Functional 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 organization of testis

 Several regulators of cell contractions are reported:

 Oxytocin

 Oxytocin-like substances

 Prostaglandins

 Androgenic steroids

 Endothelins

 Endothelin converting enzymes

 Endothelin receptors

Functional organization of testis

 These cells also secrete extracellular matrix and factors typically expressed by connective tissue cells:

 Collagen

 Laminin

 Vimentin

 Fibronectin

 Growth factors

 Fibroblast

Functional 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 organization of testis

 The Cytoplasm of sertoli cells contains:

 Eendoplasmic reticulum

 Smooth type

 Rough type

 A Prominent Golgi apparatus

 Lysosomal granules

 Microtubuli and intermediate filaments

Functional organization of testis

 Another important functions of Sertoli cells:

 Final testicular volume

 Sperm production

Hormonal control of testicular function

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 or after metabolism to

DHT or estradiol.

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

 The other hormones may affect testicular funtion:

 Prolactin

 GH and IGF-I

 Insulin

 Glucocorticoids

 Thyroid hormones

 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 different factors:

 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

 The main site of androgen production in the testis is the Leydig cell.

 Since Leydig cells cannot store androgens, de novo biosynthesis takes place continuously.

 LH as the central regulatory factor controls both steroidogenesis and Leydig cell cholesterol homeostasis in vivo.

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 (DHT)

 5α-androstandiol

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 5α-

Dihydrotestosterone (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 of the muscle mass during puberty.

 Important 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 for 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

Livestock

Bull

Ram

Sperm collection times for different animals

Number of Collections

Two times per week

Boar

Daily for weeks

Two times per week

Stallion

Rooster

Natural - two times per day

Artificial - every other day

Daily

Semen properties

 Semen liquid produced by:

 Sertoli and rete testis

 Genital tract secretions

 Accessory glands secretion

Semen properties

 Special proteins in semen liquid:

 Androgen binding protein (ABP)

 Acrosin inhibitor protein

 Glycoproteins

Semen properties

 Different ions in semen liquid

 Na+

 Cl-

 K+

 Ca++

 Mg++

 Hco3-

Semen properties

 Other components in semen liquid:

 Hormones

 Vitamins

 Lipids and fatty acids

 Immunoglobulin A

 Energy sources

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 pressure

 Sperm 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 xxx (2012) xxx–xxx.

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.