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SPERMATOGENESIS
The student will be able to: (MUST KNOW)
1. Define spermatogenesis.
2. Name the steps of spermatogenesis and describe the process of spermatogenesis in each step.
3. Elucidate the factors regulating spermatogenesis.
4. Understand the importance of semen analysis.
5. Give the value of normal sperm count and list the causes and effects of decreased sperm count.
6. List the composition of semen and learn the clinical importance of prostate specific antigen.
7. Draw the diagram of a normal spermatozoa.
8. Name the abnormal sperm and their effects on fertility.
9. Know the effects of vasectomy on reproductive functions.
LEARNING OBJECTIVES
 The process of development of male germ cells into spermatozoa is known as
spermatogenesis. The primordial germ cells migrate into the gonad during embryogenesis.
 These cells later become immature germ cells, called spermatogonia. Spermatogonia are
located attached to the basement membrane of the seminiferous tubule. From puberty onward,
these cells divide mitotically to continuously supply spermatocytes that form spermatozoa.
 Course of Spermatogenesis in Life:
 Spermatogenesis begins at puberty. The germ cells remain inactive throughout childhood.
 At puberty, under the influence of increasing level of gonadotropins and testosterone, the germ
cells are activated, and spermatogenesis is initiated.
 From puberty onward, spermatogenesis continues throughout life, though the process declines
at old age.
Flowchart: Steps of spermatogenesis. Note
that, till the stage of primary spermatocyte,
each cell contains 46 chromosomes and from
secondary spermatocyte to spermatozoa,
each cell contains 23 chromosomes (number
indicated against each category of cells as 46
chromosomes and 23 chromosomes in
brackets).
STEPS OF SPERMATOGENESIS
Fig: Stages of spermatogenesis
Figs : Structure of immature (A) and mature spermatozoa (B).
STRUCTURE OF SPERMATOZOA
 In human beings, the process of formation of sperm from the spermatogonium takes 65–74
days. Sometimes, the stages of development of sperms are collectively called as spermatogenic
cycle. Each stage has a relatively constant duration:
 Spermatogonia to primary spermatocytes is 16–20 days.
 Primary spermatocytes to secondary spermatocytes is 23–25 days.
 Secondary spermatocytes to spermatids is approximately 1 day.
 Spermatids to spermatozoa is about 25 days.
 Hormones like gonadotropins or androgen influence the number of spermatozoa produced, but
not the duration of the cycle. Thus, the duration of spermatogenesis remains virtually constant.
Normally, new cycles are initiated in every 2 to 4 weeks before the completion of old cycle.
Therefore, in the tubules, cells of different stages are seen at any time. This ensures
uninterrupted supply of spermatozoa throughout life.
 Hormonal Factors
 Androgen: Androgens stimulate spermatogenesis. LH creates an elevated local concentration
of androgen in the testis by stimulating Leydig cells to secrete testosterone, and this high
intratesticular testosterone is essential for spermatogenesis.
 Estrogen: Estrogen content of the fluid in the rete testis is high and there are estrogen
receptors in the rete testis.
 LH and FSH: LH helps in spermatogenesis by producing a high local concentration of
androgen.
 It is mainly the temperature that influences spermatogenesis.
 Lower environmental temperature facilitates spermatogenesis.
 Spermatogenesis best occurs at 30–35°C.
 However, very low temperature inhibits it. Conversely, increased temperature inhibits
spermatogenesis.
 Therefore, in persons taking repeated hot bath or those who regularly use insulated
athletic support for the scrotum, sperm count is invariably less.
 Generally, sperm count is more in comfortable winter and less in intense summer.
Volume : 2–5 mL
Color : White, opalescent
Specific gravity : 1.028
Motility : >60% should be actively motile within 3 hours of collection
Count : >40 million/mL is considered normal (usually, 100 million/mL is seen normally)
Liquefaction : Should liquefy within half-an-hour
Morphology : >80% should have normal morphology
pH : 7.3 to 7.5
Fructose content : Fructose concentration is 2–7 mg/mL
Other biochemical constituents :
SEMEN ANALYSIS
1. Prostaglandins
2. Ascorbic acid
3. Flavins
4. Phosphorylcholine
5. Ergotheoneine
6. Fibrinolysin, fibrinogenase
7. Acid phosphatase
8. Zinc
9. Phospholipids
10. Cholesterol
11. Spermin
12. Citric acid
13. Phosphate
14. Bicarbonate
15. Hyaluronidase
Figs : Abnormal sperms. (A) Bifid tail; (B)
Bifid head; (C) No head; (D) Curved tail.
ABNORMALITIES
Testicular Hormones and
Testicular
Abnormalities
The student will be able to: (MUST KNOW)
1. Name the hormones secreted from testis.
2. Outline the steps of synthesis and metabolism of testosterone.
3. Describe the functions of testosterone.
4. List the secondary sex characteristics in males.
5. Comprehend the feedback regulation of testicular functions.
6. Remember the functions of inhibin, activin, and follistatin.
7. Appreciate the importance of 17-ketosteroids.
8. Learn the causes and treatment of cryptorchidism.
9. Understand the physiological basis of other testicular abnormalities.
LEARNING OBJECTIVES
 The principal steroid secreted from testis is testosterone. It is the essential hormone for
male reproduction, and its absence or decreased production leads to sterility. Primarily, it
allows the development of male reproductive organs during fetal life, controls
spermatogenesis, guides development of secondary sex characteristics, and maintains
male vigor.
 Source
 Testosterone is synthesized by the Leydig cells of testis. Testosterone is also secreted
from adrenal cortex, ovaries, and placenta. Thus, a small amount of testosterone is
secreted in females.
STEPS OF TESTOSTERONE SYNTHESIS
 About 98% of testosterone binds with plasma proteins and only 2% is free in plasma.
 The free testosterone enters the target tissues in which it is converted to its active form
dihydrotestosterone (DHT) by 5α-reductase and estradiol (17β-estradiol) by aromatase.
 Thus, testosterone acts as prohormone and DHT is the biologically active hormone.
 Dihydrotestosterone has 2–3 times more affinity than testosterone for binding with androgen
receptors.
 Dihydrotestosterone causes hypertrophy of prostate.
FATE OF TESTOSTERONE SECRETED FROM LEYDIG CELLS
MECHANISM OF ACTION
 Development of Secondary Sex Characteristics
 Changes in external genitalia: Penis enlarges in length and width. The scrotum becomes
more rugose and pigmented.
 Changes in internal genitalia: Seminal vesicles increase in size and start secreting fructose.
Prostate gland enlarges and secretion increases from prostate and bulbourethral gland.
 Growth and distribution of body hairs.
 Skin changes: In general, skin becomes tough. Secretion of sebaceous gland increases and
becomes thick.
 Development of Secondary Sex Characteristics
 Mental changes: The individual becomes more active and aggressive. He takes more
interest in opposite sex.
 Voice change: Enlargement of larynx and thickening of vocal cord occur. Therefore, voice
becomes thick and deep.
 Body configuration: General increase in body height and girth occurs (growth spurt).
 Musculoskeletal changes: Growth of long bones, pectoral girdle, and vertebral bones occurs
at puberty.
Testosterone stimulates spermatogenesis, the exact mechanism of which is not known.
It is essential for sperm production and maturation.
1. It mainly facilitates the process of spermiogenesis.
2. It initiates spermatogenesis at puberty, and then maintains it throughout adulthood
and also in old age.
In male foetus, between 8th week and 18th week, testosterone causes the
differentiation of male genitalia.
1. The development of Wolffian duct into epididymis, vas deferens, and seminal
vesicles depends directly on the effects of androgen.
2. Also, the differentiation of urogenital sinus and genital tubercle into penis, scrotum,
and testis is mediated by testosterone and DHT.
3. Further, descent of testis into scrotum is promoted by testosterone.
Testosterone increases the synthesis of proteins and decreases its catabolism. This
results in increased growth and development of bones and muscles.
1. It causes sodium, potassium, calcium, phosphate, and water retention from kidney.
2. It is used as an anabolic drug in patients suffering from wasting diseases. Athletes
use it as anabolic steroids.
Many areas in the brain have androgen receptors. However, the receptors are densely
located in limbic areas, especially in amygdala and septum, and in hypothalamus,
pituitary, and preoptic area.
1.In these areas, testosterone is aromatized to estrogen.
2.Sexual dimorphism of neurons in the brain with respect to their distribution, size,
number, and activity has been reported in preoptic area and amygdala.
Inhibin
 Source
 Inhibin is secreted from Sertoli cells of testes in males and granulosa cells of ovaries in
females.
 Functions
 The main function of inhibin is to provide feedback signal to inhibit FSH secretion from
anterior pituitary. Inhibin B mainly inhibits FSH secretion.
Activin
It is a polypeptide hormone with molecular weight of 30,000.
Activin is produced by Sertoli cells.
1. It stimulates secretion of FSH.
2. Activin results from various combinations of βA and βB subunits of inhibin that forms βAβB, βBβB,
and βAβA.
3. They stimulate WBC development in the bone marrow, formation of mesoderm during embryonic life,
and also gonadal development.
Follistatin
Follistatin is a single-chain protein having molecular weight of about 40,000. It has various
isoforms that bind and inactivate activin.
1. When activins bind with follistatin, they lose their functions.
2. Thus, FSH secretion is reduced from pituitary cells.
3. Follistatin influences developing spermatogenic cells by a paracrine mechanism.
Cryptorchidism
 The failure of migration of testis from abdominal cavity into the scrotum during fetal development
is called undescended testis or cryptorchidism. The usual site of undescended testis is inguinal
rings.
1. From posterior wall of the abdomen testis first descends into the inguinal region, and then
from there into the scrotum.
2. The descent from abdomen into the inguinal region depends on MIS.
3. The descent from inguinal region to scrotum depends on testosterone and other factors.
4. Descent of testis normally completes in few days before the birth.
Treatment
Treatment with gonadotropin hormones facilitates the descent of testis. Surgical
correction is required when the hormonal treatment fails.
Complications
Undescended testis decreases sperm production, as temperature is high in the
abdomen. The incidence of malignant tumors is significantly more in undescended
testis.
Hypergonadotropic Hypogonadism
 If this occurs due to testicular dysfunctions, plasma level of gonadotropin is increased.
Hypogonadotropic Hypogonadism
 This occurs mainly due to tumor of hypothalamus or pituitary. Gonadotropin level in plasma is depressed.
 If hypogonadism occurs after puberty, the secondary sex characteristics regress slowly as androgenic
maintenance of these features is less essential. However, loss of libido is common.
 If loss of Leydig cells occurs from childhood, eunuchoidism results.
 Eunuchoid are usually tall, with narrow shoulders and less muscular development.
 The genitalia are small.
 Though pubic hairs are present, they are usually sparse and exhibit female pattern, i.e. triangle with base-
up.

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Spermatogenesis

  • 2. The student will be able to: (MUST KNOW) 1. Define spermatogenesis. 2. Name the steps of spermatogenesis and describe the process of spermatogenesis in each step. 3. Elucidate the factors regulating spermatogenesis. 4. Understand the importance of semen analysis. 5. Give the value of normal sperm count and list the causes and effects of decreased sperm count. 6. List the composition of semen and learn the clinical importance of prostate specific antigen. 7. Draw the diagram of a normal spermatozoa. 8. Name the abnormal sperm and their effects on fertility. 9. Know the effects of vasectomy on reproductive functions. LEARNING OBJECTIVES
  • 3.  The process of development of male germ cells into spermatozoa is known as spermatogenesis. The primordial germ cells migrate into the gonad during embryogenesis.  These cells later become immature germ cells, called spermatogonia. Spermatogonia are located attached to the basement membrane of the seminiferous tubule. From puberty onward, these cells divide mitotically to continuously supply spermatocytes that form spermatozoa.
  • 4.  Course of Spermatogenesis in Life:  Spermatogenesis begins at puberty. The germ cells remain inactive throughout childhood.  At puberty, under the influence of increasing level of gonadotropins and testosterone, the germ cells are activated, and spermatogenesis is initiated.  From puberty onward, spermatogenesis continues throughout life, though the process declines at old age.
  • 5. Flowchart: Steps of spermatogenesis. Note that, till the stage of primary spermatocyte, each cell contains 46 chromosomes and from secondary spermatocyte to spermatozoa, each cell contains 23 chromosomes (number indicated against each category of cells as 46 chromosomes and 23 chromosomes in brackets). STEPS OF SPERMATOGENESIS
  • 6. Fig: Stages of spermatogenesis
  • 7. Figs : Structure of immature (A) and mature spermatozoa (B). STRUCTURE OF SPERMATOZOA
  • 8.  In human beings, the process of formation of sperm from the spermatogonium takes 65–74 days. Sometimes, the stages of development of sperms are collectively called as spermatogenic cycle. Each stage has a relatively constant duration:  Spermatogonia to primary spermatocytes is 16–20 days.  Primary spermatocytes to secondary spermatocytes is 23–25 days.  Secondary spermatocytes to spermatids is approximately 1 day.  Spermatids to spermatozoa is about 25 days.
  • 9.  Hormones like gonadotropins or androgen influence the number of spermatozoa produced, but not the duration of the cycle. Thus, the duration of spermatogenesis remains virtually constant. Normally, new cycles are initiated in every 2 to 4 weeks before the completion of old cycle. Therefore, in the tubules, cells of different stages are seen at any time. This ensures uninterrupted supply of spermatozoa throughout life.
  • 10.  Hormonal Factors  Androgen: Androgens stimulate spermatogenesis. LH creates an elevated local concentration of androgen in the testis by stimulating Leydig cells to secrete testosterone, and this high intratesticular testosterone is essential for spermatogenesis.  Estrogen: Estrogen content of the fluid in the rete testis is high and there are estrogen receptors in the rete testis.  LH and FSH: LH helps in spermatogenesis by producing a high local concentration of androgen.
  • 11.  It is mainly the temperature that influences spermatogenesis.  Lower environmental temperature facilitates spermatogenesis.  Spermatogenesis best occurs at 30–35°C.  However, very low temperature inhibits it. Conversely, increased temperature inhibits spermatogenesis.  Therefore, in persons taking repeated hot bath or those who regularly use insulated athletic support for the scrotum, sperm count is invariably less.  Generally, sperm count is more in comfortable winter and less in intense summer.
  • 12. Volume : 2–5 mL Color : White, opalescent Specific gravity : 1.028 Motility : >60% should be actively motile within 3 hours of collection Count : >40 million/mL is considered normal (usually, 100 million/mL is seen normally) Liquefaction : Should liquefy within half-an-hour Morphology : >80% should have normal morphology pH : 7.3 to 7.5 Fructose content : Fructose concentration is 2–7 mg/mL Other biochemical constituents : SEMEN ANALYSIS 1. Prostaglandins 2. Ascorbic acid 3. Flavins 4. Phosphorylcholine 5. Ergotheoneine 6. Fibrinolysin, fibrinogenase 7. Acid phosphatase 8. Zinc 9. Phospholipids 10. Cholesterol 11. Spermin 12. Citric acid 13. Phosphate 14. Bicarbonate 15. Hyaluronidase
  • 13. Figs : Abnormal sperms. (A) Bifid tail; (B) Bifid head; (C) No head; (D) Curved tail. ABNORMALITIES
  • 15. The student will be able to: (MUST KNOW) 1. Name the hormones secreted from testis. 2. Outline the steps of synthesis and metabolism of testosterone. 3. Describe the functions of testosterone. 4. List the secondary sex characteristics in males. 5. Comprehend the feedback regulation of testicular functions. 6. Remember the functions of inhibin, activin, and follistatin. 7. Appreciate the importance of 17-ketosteroids. 8. Learn the causes and treatment of cryptorchidism. 9. Understand the physiological basis of other testicular abnormalities. LEARNING OBJECTIVES
  • 16.  The principal steroid secreted from testis is testosterone. It is the essential hormone for male reproduction, and its absence or decreased production leads to sterility. Primarily, it allows the development of male reproductive organs during fetal life, controls spermatogenesis, guides development of secondary sex characteristics, and maintains male vigor.  Source  Testosterone is synthesized by the Leydig cells of testis. Testosterone is also secreted from adrenal cortex, ovaries, and placenta. Thus, a small amount of testosterone is secreted in females.
  • 18.  About 98% of testosterone binds with plasma proteins and only 2% is free in plasma.  The free testosterone enters the target tissues in which it is converted to its active form dihydrotestosterone (DHT) by 5α-reductase and estradiol (17β-estradiol) by aromatase.  Thus, testosterone acts as prohormone and DHT is the biologically active hormone.  Dihydrotestosterone has 2–3 times more affinity than testosterone for binding with androgen receptors.  Dihydrotestosterone causes hypertrophy of prostate.
  • 19. FATE OF TESTOSTERONE SECRETED FROM LEYDIG CELLS
  • 20.
  • 22.
  • 23.
  • 24.  Development of Secondary Sex Characteristics  Changes in external genitalia: Penis enlarges in length and width. The scrotum becomes more rugose and pigmented.  Changes in internal genitalia: Seminal vesicles increase in size and start secreting fructose. Prostate gland enlarges and secretion increases from prostate and bulbourethral gland.  Growth and distribution of body hairs.  Skin changes: In general, skin becomes tough. Secretion of sebaceous gland increases and becomes thick.
  • 25.  Development of Secondary Sex Characteristics  Mental changes: The individual becomes more active and aggressive. He takes more interest in opposite sex.  Voice change: Enlargement of larynx and thickening of vocal cord occur. Therefore, voice becomes thick and deep.  Body configuration: General increase in body height and girth occurs (growth spurt).  Musculoskeletal changes: Growth of long bones, pectoral girdle, and vertebral bones occurs at puberty.
  • 26. Testosterone stimulates spermatogenesis, the exact mechanism of which is not known. It is essential for sperm production and maturation. 1. It mainly facilitates the process of spermiogenesis. 2. It initiates spermatogenesis at puberty, and then maintains it throughout adulthood and also in old age.
  • 27. In male foetus, between 8th week and 18th week, testosterone causes the differentiation of male genitalia. 1. The development of Wolffian duct into epididymis, vas deferens, and seminal vesicles depends directly on the effects of androgen. 2. Also, the differentiation of urogenital sinus and genital tubercle into penis, scrotum, and testis is mediated by testosterone and DHT. 3. Further, descent of testis into scrotum is promoted by testosterone.
  • 28. Testosterone increases the synthesis of proteins and decreases its catabolism. This results in increased growth and development of bones and muscles. 1. It causes sodium, potassium, calcium, phosphate, and water retention from kidney. 2. It is used as an anabolic drug in patients suffering from wasting diseases. Athletes use it as anabolic steroids.
  • 29. Many areas in the brain have androgen receptors. However, the receptors are densely located in limbic areas, especially in amygdala and septum, and in hypothalamus, pituitary, and preoptic area. 1.In these areas, testosterone is aromatized to estrogen. 2.Sexual dimorphism of neurons in the brain with respect to their distribution, size, number, and activity has been reported in preoptic area and amygdala.
  • 30. Inhibin  Source  Inhibin is secreted from Sertoli cells of testes in males and granulosa cells of ovaries in females.  Functions  The main function of inhibin is to provide feedback signal to inhibit FSH secretion from anterior pituitary. Inhibin B mainly inhibits FSH secretion.
  • 31. Activin It is a polypeptide hormone with molecular weight of 30,000. Activin is produced by Sertoli cells. 1. It stimulates secretion of FSH. 2. Activin results from various combinations of βA and βB subunits of inhibin that forms βAβB, βBβB, and βAβA. 3. They stimulate WBC development in the bone marrow, formation of mesoderm during embryonic life, and also gonadal development.
  • 32. Follistatin Follistatin is a single-chain protein having molecular weight of about 40,000. It has various isoforms that bind and inactivate activin. 1. When activins bind with follistatin, they lose their functions. 2. Thus, FSH secretion is reduced from pituitary cells. 3. Follistatin influences developing spermatogenic cells by a paracrine mechanism.
  • 33.
  • 34. Cryptorchidism  The failure of migration of testis from abdominal cavity into the scrotum during fetal development is called undescended testis or cryptorchidism. The usual site of undescended testis is inguinal rings. 1. From posterior wall of the abdomen testis first descends into the inguinal region, and then from there into the scrotum. 2. The descent from abdomen into the inguinal region depends on MIS. 3. The descent from inguinal region to scrotum depends on testosterone and other factors. 4. Descent of testis normally completes in few days before the birth.
  • 35. Treatment Treatment with gonadotropin hormones facilitates the descent of testis. Surgical correction is required when the hormonal treatment fails. Complications Undescended testis decreases sperm production, as temperature is high in the abdomen. The incidence of malignant tumors is significantly more in undescended testis.
  • 36. Hypergonadotropic Hypogonadism  If this occurs due to testicular dysfunctions, plasma level of gonadotropin is increased. Hypogonadotropic Hypogonadism  This occurs mainly due to tumor of hypothalamus or pituitary. Gonadotropin level in plasma is depressed.  If hypogonadism occurs after puberty, the secondary sex characteristics regress slowly as androgenic maintenance of these features is less essential. However, loss of libido is common.  If loss of Leydig cells occurs from childhood, eunuchoidism results.  Eunuchoid are usually tall, with narrow shoulders and less muscular development.  The genitalia are small.  Though pubic hairs are present, they are usually sparse and exhibit female pattern, i.e. triangle with base- up.