MALE REPRODUCTIVE SYSTEM. Objectives At the end of the topic, the students should be able to :...

MALE REPRODUCTIVE SYSTEM

Objectives

At the end of the topic, the students should be able to :Explain the functions of the testis

Discuss spermatogenesis

Describe the characteristics of a normal sperm

Explain the role of FSH and inhibin on spermatogenesis

Discuss the contents of semen and its abnormalities

Explain the functions of testosterone

Explain the control of secretion of testosterone 

Importance of Leydig cells and testosterone in puberty

Role of Sertoli cells,testosterone, DHT, and estrogen in spermatogenesis

How testosterone and inhibin functions in the adult feedback regulation of the Hypothalamic/ Pituitary/ Gonadal Axis

Main points in male reproductive physiology

INTRODUCTION

A pair of testes

A pair of accessory glands

Ductal system

Copulatory organ

Male reproductive system (Lateral view)

Male reproductive system (Anterior view)

Structure of testis

Seminiferous tubules

FUNCTIONS

Production of spermatozoa after puberty for fertilization with the ovum from the female

Coitus process

Produce androgens

TestisOriginates from indifferent gonads during the embryonic phaseContains lobules (200-300) separated by septumEach lobule has 4 seminiferous tubulesBlood supply is from testicular artery and blood drainage is through the Pampiniform plexus into the testicular veinSeminiferous epithelium contains Sertoli cells (Sustentacular cells) and Germ cellsLeydig cells exist in between tubulesProduce spermatozoa and androgensDivided into two compartments; extratubular and intratubular

Histology of the testis

Lumen

SCN

SpermatogoniaLeydig cells

ITC

ETC

Compartments

Extratubular – vascular and interstitial divisions (inclusive of lymphatic channels and Leydig cells)

Intratubular – basal and adluminal divisions located in the seminiferous tubules

Spermatogenesis

Spermatogenesis and spermatozoon structure

Epididymis

Blood Testis Barrier

Formed before spermatogenesis commencesFormed by Sertoli cellsFunctions :

1. Stop intratubular spermatozoa from entering systemic and lymphatic circulationThe blood testes barrier is important since sperm (with their unique surface antigens) elicit an immune response if detected by the immune cells in the man’s blood, and the antibodies that are formed against sperm are designed to immobilize and destroy them

A number of events can disrupt the blood testes barrier and allow the immune system to become activated against the sperm.

These include:• trauma to the testes• torsion (twisting) of the testes• a history of a vasectomy and reversal• any other surgery within the scrotum• infection within the testes

Allergic orchitis

Inflammation of the testis due to antisperm antibodies

2. Ensure the intratubular chemical composition is different from the intertubular chemical composition (blood, interstitial fluid and lymph)

As spermatogenesis must occur in a controlled microenvironment, any changes in the chemical composition will affect normal spermatogenesis

Functions of Sertoli cells

Sertoli cells are joined by tight junctions that provides barrier to chemicals (Blood testis barrier)Nourish developing spermSecrete luminal fluid including androgen binding proteins (ABP)Phagocytize defective spermMediate testosterone and FSH effects on spermatogenesisSecrete inhibin which inhibits FSH secretionInfluence Leydig cells via paracrine secretionsEmbryonic secretion of Mullerian Inhibiting Substance (MIS) that ensures male phenotype

Sertoli cells

Spermatogenesis

Process for formation of spermatozoaThe seminiferous tubules produce haploid cells (n)Involves several steps including mitosis and meiosisTakes about 64 days in human

Consists of three stages:1. Spermacytogenesis – formation of spermatid from

spermatogonia2. Spermiogenesis – formation from spermatid to spermatozoa3. Spermiation – the release of spermatozoa into the epididymis

SpermacytogenesisMitosis stagespermatogonia type Ad give rise to a pair of spermatogonia type Ad or Apspermatogonia type Ap give rise to a pair of spermatognia type Ap or Bmitosis of the germ cells occurs in the basal compartmentincomplete cytokenesis of committed cells (type Ap) results in the cells being linked by cytoplasmic bridges until spermatozoa is formthis linkage results in a synchronous development of the cells within a given region of the tubule

Types of cellsgerm cells - - spermatogonia (types A and B):

- spermatogonia type A - for spermatogenic lineage (type A dark (Ad) or A pale (Ap), type Ad are true stem cells)

- spermatogonia type B - progenitor cell for primary spermatocyteprimary spermatocyte (46 chromosomes, 4N DNA):

- first meiotic division from these cells result in secondary spermatocyte (23 chromosomes, 2N DNA)

- second meiotic division from these cells results in spermatidsspermatids (23 chromosomes, 1N DNA) – undergoes modifications in many parts and gives rise to spermatozoaspermatozoa, within the seminiferous tubules (and distally) the flagella is not motile

Spermiogenesisspermatid phase: spermatids develop into spermatozoa in 4 stages:Golgi phase

- development of the acrosomal granule from the Golgi complex forming the acrosomal vesicle at the nascent apex (anterior) of cell

- positioning of centrioles at the nascent base of flagella- initiation of formation of axonemal complex from one of the centrioles

Cap phase - development of acrosomal cap over nucleus and condensation of

chromatin- development of flagellum from axonemal complex- acrosome contains hydrolases (proteases, hyaluronidase, neuramidase,

acid phosphatase) important in penetration of the oocyte membrane during fertilization

SpermiogenesisAcrosome phase - spermatid re-orients so tail (flagellum) projects into the lumen of the tubule and the acrosome towards the base of the epithelium

- further condensation of chromatin- flattening and elongating of nucleus at the

anterior of the cell- movement of cytoplasm to the posterior of cell- further development of flagellum- linkage of flagellum to nucleus via the

connecting piece developed from a centrioleMaturation phase - residual body of cytoplasm shed (cell linkages lost) and the cells released by Sertoli cell into lumen of tubule

Spermiation

released spermatid moved with fluid via

peristaltic action of myoid cells transporting it to the straight tubule

sperm cannot move yet

will develop motility in epididymis

1 germ cell produces 64 spermatozoa

Process takes ~2 months (56 – 64 days ) to complete

100 million sperm produced each day

Not all are normal i.e., abnormal % increases with alcohol, heat, cigarettes, drugs

Temperature sensitivity…

Spermatogenesis is temperature sensitive, optimal 34o C

Achieved by the descent of the testes out of the abdomen

Arteries and veins supplying the testes intertwine, efficiently exchanging heat (from artery to veins) to further cool testes

Scrotum

Originates from labioscrotal swellings and urethral fold

Pouch that houses the testes

Main function is to provide an environment which is 1-80F lower than the body temperature and also to control testicular temperature

Testicular temperature needs to be controlled for spermatogenesis to occur normally

Control and regulation of testicular temperature (1)

Two muscle system – cremaster external and tunica dartos

Cremaster external muscle passes along inguinal canal and attaches to tunica vaginalis

- Pulls tunica vaginalis as it contracts when the environmental temperature drops

Tunica dartos muscle attaches to scrotal skin and forms a septum separating the scrotum

- Pulls scrotal skin as it contracts when the environmental temperature drops

Control and Regulation of testicular temperature (2)

Pampiniform plexus

– consists of convoluted veins and arteries which follow the spermatid cord into the inguinal canal. Arterial branch comes from spermatid artery and venous part enters the spermatid vein

- controls temperature by dissipating heat from the aortal blood through the convolutions before reaching the testis

The testes is located in the abdominal cavity during the fetal stageOnly descents into scrotum at 7 months of pregnancySometimes do not descend and when born, two conditions may occur i.e., cryptochidism or monochidismCrypotochidism – cryptochids are males with both testes in inguinal canal/abdominal cavity

- usually sterile- may either be hereditary or due to lack of hormones- undescended testes are associated with reduced fertility,

increased risk of testicular cancer and psychological problems when the boy is grown

- undescended testes are also more susceptible to testicular torsion, infarction and inguinal hernias

Monochidism – monochids are males with only one testis descended into scrotum, the other remained in inguinal canal/abdominal cavity

- usually fertile as one testis still functioning normally therefore spermatogenesis is not impaired

Approximately 3% of full-term and 30% of premature infant boys are born with at least one undescended testis, making monochidism/cryptorchidism the most common birth defect of male genitalia

However, most testes descend by the first year of life (the majority within three months), making the true incidence of cryptorchidism around 1% overall.

Ductal System

Originates from Wolffian ducts (mesonephric kidney)Mullerian ducts = rudiments in prostate gland (prostatic utricle/uterus masculinus) – non-functional but can grow when there is estrogen influence causing prostate cancerMesonephric tubules = vasa efferentiaMesonephric ducts = epididymis, vas deferens and seminal vesiclesUrogenital sinus = prostatic, cavernous and membranous urethra, prostate glands and Bulbo-urethral gland (Cowper’s gland)Rete testis in the testis = efferentia ducts and then becomes epididymis and vas deferens

Epididymis

Originates from mesonephric ductsDivided into caput (head), corpus (body) and cauda (tail)Extra fluid from sperm is reabsorbed to concentrate spermatozoa 100X Presence of high concentrations of testosterone/ DHT in the tubule causes epididymis to secrete a motility- inducing protein that binds to the cell membrane of sperm cellsSecrete mucoproteins/glycoproteins that coats the head of the spermAlso secretes carnitine, glycerolphosphorycholine, fructose and glycoproteinsTransit time for spermatozoa to attain maturation and the ability to move/motility is about 6 – 12 daysSpermatozoa can move forward and has the ability to fertilize ovum once has entered cauda epididymisMorphological and biochemical changes also occur

Caput

Corpus

Cauda

Vas deferens

Developed from Wolffian ducts

Vas deferens have a lot of muscle layers (inner and outer longitudinal muscle layer with circular layers in between this muscles – layers are important for sperm motility

Vas deferens form the ampulla near the bladder

Sperm enters vas deferens from epididymis

Acts as a reservoir to store spermatozoa

Also acts as a conduit between testes and urethra

Mature sperm stored in the Vas Deferens and can remain viable for up to 3 months

If no ejaculation occurs, sperm will dribble into terminal ampulla into urethra

Copulatory organ - penisOriginates from genital tubercleProvides an outlet for both urine and the copulatory ejaculate (spermatozoa and seminal plasma)Histology/anatomy of penis varies from species to species and from region to region within the same speciesBody of the penis consists of:

- the urethra- erectile tissue (corpora cavernosa penis and corpora cavernosum

urethra), cavernous bodies act as erectile tissues where it can be engorged with blood to erect the penis

- touch and pressure receptors (Pacinian corpuscles)- a dense connective tissue capsule (tunica albuginea- tip of penis is called glans penis and in humans it is mushroom-shaped

Penis

Accessory glands

A pair of seminal vesicles, prostate glands and bulbo-urethral glands (Cowper’s glands)

Originates from urogenital sinus and mesonephric ducts

Produces seminal plasma which is the fluid component of semen

seminal vesicle empties contents into ampulla- tubuloalveolar gland - yellowish secretory product and contains fructose, citrate, ascorbic acid, inositol,

prostaglandins and proteins- fructose is an important energy source for spermatozoa- 70% of ejaculate (semen) derives from the seminal vesicles- secretory activity stimulated by testosterone

prostrate gland empties contents into the prostatic urethra- prostrate is a branched tubuloalveolar gland - secretions include acid phosphatase, amylase, and fibrinolysin- gland wraps around prostatic urethra and empties into it- glycoprotein deposits develop and can become calcified, these are called prostatic

concretions or corpora amylacea and are a characteristic feature of the adult prostrate- secretory activity stimulated by testosterone- hyperplasia occurs within the gland with increasing age, gradually decreasing the

diameter of the urethra and slowing urine voiding

bulbourethral (Cowper’s) gland empty into the post-prostatic urethra

- tubuloalveolar glands that secrete a lubricating mucous that contains galactose, galactosamine, galacturonic acid, sialic acid, and methylpentose

- secretions precede other ejaculatory products and release involves the oxytocin axis

- secretory activity of epithelia stimulated by testosterone

Seminal plasma

Three functions: 1) as a media that provides the

suspension/vehicle and also activation to spermatozoa

2) provides electrolytes, nitrogen, citric acid, fructose etc for nutrition

3) provides an alkaline pH to semen to combat acidity of vagina

SpermatozoaA very simple cell but highly adapted for reaching and penetrating the ovumBasically have head, midpiece and tailDifferent sizes in different speciesHead shape may be paddle (human, rabbit, bull, ram), cylindrical (cockerel) or hooked (rodent species)Acrosome in the head contains hydrolytic enzymes for digesting cells around ovum; can also digests sperm upon deathCarries the necessary package for fertilization (enzymes and chromosomes) Needs to travel light as main function is for fertilizationTail contains mitochondria that provides ATP for energy for increased motility to reach ovum before sperm diesTail have 9 + 2 doublets arrangement called axonemeHas no energy reserves, hence has a limited life span once released (48 – 72 hrs)Dies by degeneration (hydrolytic enzymes in acrosome destroy sperm upon death)

Spermatozoa

Rat sperm Rabbit sperm

Human sperm Chicken sperm

Sperm motility

SemenEjaculate - spermatozoa and seminal plasma By volume <10 % sperm Accessory Glands: 60 % seminal vesicle,10 % bulbourethral, 30 % prostate Usually ph 7 to 7.4 Coagulate after ejaculation in humanCoagulation is important so that sperm number that enters vagina is maintainedLiquefaction of semen occurs usually before 30 minsLiquefaction is due to enzyme-substrate interactionThe liquefaction time denotes semen quality: the longer the liquefaction time, the lower is the quality. WHY? As the life span of sperm is only about 72 hours, the sperm will need to break free from the gel ASAP to enable it to swim up to meet the ovum

Normal semen values (WHO,1999)

Volume 2 – 3 ml

Liquefaction time ideally 30 mins)

Colour Milky

Viscosity Fairly watery

pH 7 – 7.2

Motility 50 – 60%

Count > 20 million/ml

Viability > 50%

Normal morphology variable 30%

Terms

Normospermia/normozoospermia (normal semen values)

Azoospermia – no sperm found in sample

Oligospermia – less than 20 million/ml sperm

Asthenozoospermia – sperm present but non-motile

Necrozoospermia – high number of dead sperm

Teratozoospermia – high number of abnormal sperm

Regulation of spermatogenesis

Prepubertal LH and FSH are low, thus testes activity is low

Between the ages of 13 and 20 the hypothalamic/ pituitary/ gonadal axis is reactivated (puberty)]

The precise trigger is not known…

– could be percentage body adipose tissue

– could be pineal gland/ melatonin involvement

Regulation of testicular function

GnRH released every 2- 3 hours

Results in a pulsatile release of LH and FSH

Testosterone from Leydig cells inhibits both the release of LH and GnRH

Inhibin from Sertoli cells inhibits the release of FSH (but not LH or GnRH).

Hormonal influence

GnRH from hypothalamus goes to anterior pituitary – FSH and LH are released

LH (Interstitial Cell Stimulating Hormone/ICSH) goes to Leydig cells to initiate production of testosterone

FSH and testosterone stimulates Sertoli cell (Sustentacular cells) to increase enzyme activity (5-reductase, aromatase) and synthesis Androgen Binding Proteins (ABP)

ADP will bind to testosterone causing level of testosterone in lumen of seminiferous tubules to rise

Sustentacular cells also produce inhibin (a peptide hormone)

FSH and LH only acts on testis but testosterone influences testis and initiate development of sexual organs and male secondary sexual characteristics

Control of testosterone secretion

When testosterone and inhibin levels in the blood are high, two negative feedback mechanisms are initiated to regulate the spermatogenic process

When levels of circulating testosterone are high in the blood, this high testosterone will send a negative feedback mechanism to hypothalamus to inhibit LH release

Control of sperm production

When there are >20 million spermatozoa in the testicles, inhibin will send a negative feedback mechanism to the hypothalamus to inhibit the release of FSH

This two negative feedback mechanisms are terminated when level of testicular spermatozoa falls below 20 million and testosterone level falls below required level for normal spermatogenesis

Functions of testosterone

Produced by the Interstitial cells of Leydig under influence of LH and GnRH

Testosterone has a number of functions- Promotes maturation of sperm cells - Maintains male 2nd sex organs - Determines secondary male characteristics (wide

shoulders, narrow hips, body hair patterns, enlargement of thyroid cart of larynx, deepens voice)

- Stimulates bone and muscle growth, epiphysial closure, protein metabolism