Physiology of Reproduction

Dr Prof Dr Adeela
Aneela Amjad Shahid
MBBS,
DPT, M.PhiL,
MPhil PhD
Physiology
SMDC
 OBJECTIVES:
• At the end of Lecture students should be able
to:
– Explain physiological anatomy of Male
reproductive system
– Discuss spermatogenesis
– Elaborate Spermiogenesis
– Explain functions of prostate, seminal vesicles
– Describe Capacitation of spermatozoa
– Explain Acrosome reaction
 Reproduction
• Reproductive System
– Not needed for the survival of the individual
– Species survival
• Sexual reproduction
– Genes from two individual
– Combine at random
– Creates new combinations
– Increases chances of species survival
Male reproductive system
 Male reproductive system
• Testis made up of seminiferous tubule
• Epididymis
• Vas deferens
– Which enlarges into the ampulla of the vas deferens &
enters into Prostate gland
• Prostate gland
• Two seminal vesicles on either side of prostate
• Emptying into Prostatic end of Ampulla
• contents from ampulla, seminal vesicles & prostate pass
into an ejaculatory duct.
• Which empties into the internal urethra
Cross Section of a Seminiferous Tubules
Stages in the Development of Sperm from
Spermatogonia
 Spermatogenesis
• During formation of the
embryo
• Primordial germ cells migrate
into the testes and become
immature germ cells called
spermatogonia
• Spermatogonia lie in two or
three layers of the inner
surfaces of the seminiferous
tubules
 Spermatogenesis
• Spermatogonia:
–undergo mitotic division which begins
at puberty due to stimulation by
anterior pituitary Gonadotropic
hormones (FSH, LH)
–Produce two cells
• Becomes Primary spermatocytes by
Mitosis
Stages in the development of sperm from
spermatogonia
Spermatogonia:
Primary spermatocytes formed by
Mitosis
 Spermatogenesis (cont……)
• Primary spermatocytes undergoes meiotic
division :
– Form two secondary spermatocytes
– These too divide to form spermatids
– Spermatids are modified to become
spermatozoa
– 46 chromosomes in spermatocytes are
divided
– 23 chromosomes go to one spermatid and
the other 23 to the second spermatid
Primary spermatocytes undergoes
meiotic division
 Sexual Reproduction
• Each individual produces gametes
– Formed in gonads (Testes / Ovaries) by meiosis
• Male: testes produce
– Sperms
– Testosterone
• Female: ovaries produce
– Ova
– Estrogens, Progesterone
• Gametes (Sperm & Ova) unite in the process of fertilization
– Restores diploid number
– Forms zygote
 Sexual Determination
• Each zygote inherits
– 23 chromosomes from mother
– 23 chromosomes from father
• 23 pairs of homologous chromosomes
–chromosomes having the same genes at the same
loci
• Kinds of chromosomes
– 1-22 pairs of chromosomes: autosomal
– 23rd pair are sex chromosomes.
• Male: XY
• Female: XX
• Gender of zygote is determined by fertilizing sperm.
 Sex Chromosomes
• In each spermatogonium, one pair of chromosomes carries the
genetic information that determines the sex
• It is composed of one X chromosome called the female
chromosome, and one Y chromosome called the male
chromosome.
• During meiotic division
– Y chromosome goes to one spermatid that then becomes a
male sperm
– X chromosome goes to another spermatid that becomes a
female sperm.
• The sex of the eventual offspring is determined by which of
these two types of sperm fertilizes the ovum
 Formation of Testes
• First 40 days after conception the gonads of males and
females are similar in appearance.
• During this time:
– Spermatogonia and oogonia migrate from yolk sac to
developing embryonic gonads
– Gonads could become either testes or ovaries
depending on the presence of.
• TDF (testis-determining factor):
– promotes the conversion of embryonic gonads to
testes:
• Gene for TDF is located on short arm of Y, called SRY
(sex determining region of Y chromosome)
 Formation of Testes
• First 40 days after
conception the gonads
of males and females
are similar in
appearance.

•Gonads could become either testes or ovaries depending

on the presence or absence of TDF (testis-determining
factor):
• TDF promotes the conversion of embryonic gonads to
testes
• Gene for TDF is located on short arm of Y, called SRY (sex
determining region of Y chromosome)
 Development of Accessory Sex Organs & Genitalia
• Presence or absence of testes determines the accessory sex
organs and external genitalia.
• Female accessory organs derived from mullerian ducts
(Paramesonephritic)
• Fetal Sertoli cells secrete MIF (mullerian inhibition factor)
• MIF inhibits development of female accessory organs in
male baby. Male accessory organs derived from wolffian
ducts (Mesonephric)
• MIS continues to be secreted by the Sertoli
cells, and it reaches mean values of 48 ng/mL in
plasma in 1- to 2-year-old boys.
– Thereafter, it declines to low levels by the time of
puberty and persists at low levels throughout life.
• Testosterone is secretion starts at 8th week of
IUL and peak levels are achieved at 12- 14th
week of IUL
– secreted for the 10 weeks after birth then the levels
decline and increases after puberty in males
• MIS and testosterone act unilaterally.
• MIS causes regression of the mullerian ducts
by apoptosis on the side on which it is
secreted
• Testosterone stimulates the development of
the vas deferens and Epididymis from the
wolffian ducts.
• The testosterone metabolite
dihydrotestosterone (DHT) induces the
formation of male external genitalia and male
secondary sex characteristics
 Testes
• Structures in the testes:
– Seminiferous tubules:
– 900 coiled seminiferous tubules are present in testes.
– more than one half meter long, in which the sperm are
formed.
– Site where spermatogenesis occurs.
• Germinal cells: sperm
• Nongerminal cells: Sertoli cells (sustentacular cells)
– Contain receptors for FSH
– Leydig cells (interstitial cells):
• Contain receptors for LH
• Secrete Testosterone, androsterone &
dehydroepianrdosterone when stimulated by LH
 Formation & Structure of a Sperm
• When the spermatids are first formed, they are
like epithelioid cells
• They differentiate and elongate into
spermatozoa.
• Head and a tail is formed.
• The head is a condensed nucleus with a thin
cytoplasmic and cell membrane layer around it
• On the anterior two thirds of the head is a thick
cap called acrosome formed by the Golgi
apparatus
 Structure of sperm
• Acrosome contains
– Hyaluronidase
• It is an enzyme that depolymerizes the
mucopolysaccharide hyaluronic acid, which
is a component of the ground substance or
tissue cement (digest proteoglycan
filaments of tissues)
– Proteolytic enzymes (digest proteins)
• These enzymes allow the sperm to enter the
ovum and fertilize it.
 Flagellum
• Tail / flagellum has three major
components:
– Central skeleton (axoneme)
made up of 11 microtubules
– Thin cell membrane covering
the axoneme
– Collection of mitochondria
surrounding the axoneme in
the proximal portion/body of
the tail).
Cross Section of a Seminiferous Tubules
 Sertoli Cells
• Form Blood-testes barrier:
– Prevents autoimmune destruction of sperm.
• Contain aromatase (CYP19) enzyme that converts
testosterone to estrogen
• Sertoli cells secrete Inhibin, mullerian inhibiting substance
(MIS)
– MIS causes regression of the mullerian ducts by apoptosis
– Inhibin inhibits FSH secretion
• Phagocytize residual bodies
• Secrete androgen-binding protein (ABP):
– Binds to testosterone and concentrates testosterone in the
tubules.
 Testes
• Leydig cells secrete testosterone
– Begins at 8th week of IUL and peaks at 12-14th
week
– Testosterone masculinizes embryonic
structures
• Testes descend into scrotum shortly before birth
– Temp in scrotum is about 30C below internal
temp.
 Formation of Ovaries
• Absence of Y chromosome and TDF (testis-
determining factor) results in development of
ovaries.
• Ovarian follicles do not appear until 3nd
trimester.
• In both sexes gonads secrete other polypeptides,
including inhibin B, a polypeptide that inhibits
follicle stimulating hormone (FSH) secretion
 Formation of Sperm
/Spermiogenesis
• Maturation of
spermatozoa.
• Cytoplasm is
pinched off and
ingested by the
Sertoli cell
cytoplasm.
Structure of spermatozoon
 Hormonal Factors That Stimulate
Spermatogenesis
• Testosterone
• Luteinizing hormone
• Follicle-stimulating hormone
• Estrogens
• Growth hormone
• Testosterone
– Causes growth and division of the testicular
germinal cells
• Luteinizing hormone
– stimulates the Leydig cells to secrete
testosterone
• Follicle-stimulating hormone
– stimulates the Sertoli cells ,without this
stimulation, the conversion of the spermatids
to sperm will not occur
• Estrogens
– FSH stimulate Sertoli cells which convert
testosterone to estrogen, it is essential for
Spermiogenesis
• Growth hormone
– controls background metabolic functions of the
testes
– promotes early division of the Spermatogonia
 Maturation of Sperm in the Epididymis
• Sperms are nonmotile in the seminiferous tubules
and in the early portions of the Epididymis
• After 18 to 24 hours in the Epididymis they
become motile
• There are several inhibitory proteins in the
epididymal fluid which still prevent final motility
 Storage of Sperm in the Testes
• 120 million sperm are formed by testes each day
• sperm are stored in the Epididymis
• small quantity is also stored in the vas deferens
• Sperms are kept in inactive state by multiple
inhibitory substances in the secretions of the ducts
 FUNCTION OF THE SEMINAL VESICLES
• Each seminal vesicle is a tortuous, loculated tube with a
secretory epithelium
• Secretes a mucoid secretion
– Contains fructose, citric acid, prostaglandins, fibrinogen, and other
nutrient substances
• Seminal vesicle empties its contents into the ejaculatory
duct
• Prostaglandins help the fertilization in two ways:
– React with cervical mucus to make it more receptive for sperm
movement
– Cause reverse peristaltic contractions in uterus & fallopian tubes
to move the sperm toward the ovaries
 FUNCTIONS OF THE PROSTATE GLAND
• Prostatic fluid is Alkaline in nature
• It contains calcium, citrate ion, phosphate ion, a clotting enzyme,
and a profibrinolysin.
• Alkaline fluid is important for fertilization of the ovum
– Fluid of the vas deferens is acidic due to the presence of citric
acid and metabolic end products of the sperm which inhibit
sperm fertility
– Vaginal secretions are also acidic (with a pH of 3.5 to 4.0)
– Sperm do not become motile until the pH rises to about 6.0 to
6.5
– Prostatic fluid helps neutralize the acidity and enhances the
motility and fertility of the sperm
 OBJECTIVES:
• At the end of Lecture students should be able to:
– Describe Capacitation of spermatozoa
– Explain Acrosome reaction
– Explain the development of testes
– Describe blood tests barrier
– Discuss male infertility
– Elaborate metabolism, secretion, mechanism and
functions of testosterone
CAPACITATION OF
SPERMATOZOA
Obstacles
 Capacitation of Spermatozoa

• Sperm Capacitation refers

to the physiological
changes spermatozoa must
undergo in order to have
the ability to penetrate and
fertilize an egg.
• It is the preparation of
spermatozoa to penetrate
ovum
Capacitation of Spermatozoa (cont….)
• Spermatozoa are unable to fertilize the ovum
when secreted
• Multiple changes occur when sperm comes in
contact with the fluids of the female genital
tract, these changes activate the sperm for
fertilization. These collective changes are
called Capacitation of the spermatozoa
• Importance of Capacitation:
– Capacitation is required for fertilization of
the Ovum
Capacitation of Spermatozoa
 Following changes occur in Capacitation:
• It requires from 1 to 10 hours.
1. Inhibitory factors that suppress sperm activity are washed away by
uterine and fallopian tube fluids
2. Spermatozoa are continually exposed to cholesterol in floating
vesicles coming from the seminiferous tubules.
– Cholesterol is continually added to the cell membrane of
acrosome, toughening this membrane and preventing release
of its enzymes.
– In female genital tract sperms are deprived of the cholesterol
vesicles move into the uterine cavity
– They gradually lose excess cholesterol during the next few
hours.
– Membrane of the acrosome becomes weak
 Capacitation of Spermatozoa
3. The membrane becomes permeable to calcium ions
– Calcium enters the sperm in abundance
– Activity of the flagellum increases
– Flagellum achieves powerful whiplash motion
– Calcium ions cause changes in the cell membrane of
the acrosome to release its enzymes rapidly and easily,
when the sperm penetrates the granulosa cell mass
and the zona pellucida of the ovum
 ACROSOME REACTION

Reaction that occurs in the acrosome of the sperm

as it approaches the egg is called acrosome
reaction
STRUCTURE OF OVUM
 STRUCTURE OF OVUM
• Zona Pellucida
– Thick membrane
– Form protective coat
• Corona radiata
– 2-3 layers of cells attached cells
to zona pellucida
• Vitteline membrane
– Plasma membrane of egg cell
– Controls entry and exit of
substances
 Acrosome Reaction
• Reaction that occurs in the acrosome of the sperm as it
approaches the egg is called Acrosome reaction
• When the ovum is expelled from the ovarian follicle into
the fallopian tube, it carries multiple layers of granulosa
cells called corona radiata
• These granulosa cell layers must dissolute before a sperm
can fertilize the ovum
• Sperm must penetrate through the zona pellucida which is
a thick covering of the ovum
• When the sperm reaches the zona pellucida of the ovum,
the membrane of the sperm binds with receptor proteins in
the zona pellucida
Acrosome Reaction (continued)

Vittilline layer
 Acrosome Reaction (continued)
• Acrosome is rapidly dissolved and all the acrosomal enzymes
are released
– Hyaluronidase depolymerizes the hyaluronic acid polymers
in the intercellular cement that holds the ovarian granulosa
cells together and makes pathways between the granulosa
cells so that sperm can reach the ovum.
– The proteolytic enzymes digest proteins in the cells that still
adhere to the ovum and open pathway for passage of the
sperm head through the zona pellucida to the inside of the
ovum
– Within 30 minutes, the cell membranes of the sperm head
and of the oocyte fuse with each other & Genetic material of
the sperm and the oocyte combine to form zygote
Acrosome Reaction
 Why Does Only One Sperm Enter the
Oocyte?
• When the first sperm penetrates the zona pellucida of
the ovum
• Ca ions diffuse inward through the oocyte membrane
• After few minutes multiple cortical granules are released
from the oocyte by exocytosis into the perivitelline
space
• These granules contain substances that permeate all
portions of the zona pellucida and prevent binding of
additional sperm, and fall off those sperms that have
already begun to bind.
BLOOD–TESTIS BARRIER
 Blood–Testis Barrier
• Blood–testis barrier is formed by tight junctions,
adherens junctions and gap Junctions between
the Sertoli cells near the basal lamina.
• The walls of the seminiferous tubules are lined
by primitive germ cells and Sertoli cells which
are large complex glycogen-containing cells that
stretch from the basal lamina of the tubule to the
lumen
• Germ cells must stay in contact with Sertoli cells
to survive, the contact is maintained by
cytoplasmic bridges.
 Blood–Testis barrier
• Steroids penetrate this barrier easily
• Some proteins pass from the Sertoli cells to the
Leydig cells and vice versa in a paracrine fashion
• Maturing germ cells must pass through the barrier
as they move to the lumen
– By progressive breakdown of the tight junctions
above the germ cells along with formation of
new tight junctions below them
 Functions of Blood–Testis Barrier
• Blood–testis barrier prevents many large molecules
to pass from the interstitial fluid or blood and the
basal lamina into the lumen or near the lumen of
seminiferous tubules
• Protects the germ cells from blood borne
noxious agents
• Prevents antigenic products of dividing germ
cells from entering the circulation and generating
an autoimmune response
– Prevents autoimmune destruction of sperm
 Functions of blood–testis barrier (continued)
• Composition of fluid in seminiferous tubule is
maintained by blood–testis barrier
– Fluid in the seminiferous tubule is:
• rich in androgens, estrogens, K+, inositol, and
glutamic and aspartic acids
• Contains little protein and glucose also
• Help to establish an osmotic gradient that
facilitates movement of fluid into the tubular
lumen.
 Sertoli Cells
• Form Blood-testes barrier:
– Prevents autoimmune destruction of sperm.
• Contain aromatase (CYP19) enzyme that converts testosterone
to estrogen
• Sertoli cells secrete Inhibin, mullerian inhibiting substance
(MIS)
– MIS causes regression of the mullerian ducts by apoptosis
– Inhibin inhibits FSH secretion
• Phagocytize residual bodies
• Secrete ABP (androgen-binding protein):
– Binds to testosterone and concentrates testosterone in the
tubules.
TESTOSTERONE AND OTHER
MALE SEX HORMONES
 MALE SEX HORMONES
• Androgen means any steroid hormone that has
masculinizing effect
• The testes secrete several male sex hormones
– Inhibin
– MIS
– Testosterone
– Dihydrotestosterone
– Androstenedione
– Oestradiol
– Insulin like factor 3
 MALE SEX HORMONES (continued)
• Testosterone is secreted by the Interstitial Cells
of Leydig in the Testes
– Leydig cells are numerous in the newborn
male infant for the first few months of life and
in the adult male after puberty
– In new born and after puberty the testes
secrete large quantities of testosterone
– Leydig cells are almost non existent in the
testes during childhood when the testes
secrete almost no testosterone
 Testosterone
• Testosterone is secreted in excess &
considered to be the primary testicular
hormone
• Most of the testosterone is eventually
converted into the more active
hormone Dihydrotestosterone (DHT)
• It is also converted to Estrogen by the
Sertoli cells
 Enzymes in Leydig cells
• 11β-hydroxylase and 21 β -hydroxylase (adrenal
cortex) are absent in the Leydig cells
• Leydig cells contain 17α-hydroxylase
• Hence Pregnenolone is converted to 17 alpha
hydroxypregnenolone
• 17 alpha hydroxypregnenolone is converted to
DHEA
• DHEA is converted to Androstenedione
• DHEA and Androstenedione are then converted to
Testosterone
Biosynthesis of Testosterone
 Derivatives of testosterone
• Dehydroepiandrosterone (DHEA)

• Androstenedione Estrone Estriol

• Testosterone DHT

• Estradiol

• Estriol
 Secretion of Androgens Elsewhere in
the Body
• Adrenal gland
• Ovaries
• Placenta
– Adrenogenital syndrome
• Excess quantities of androgenic hormones are
produced that causes male secondary sexual
characteristics to occur, even in the female.
– Arrhenoblastoma
• Tumor of embryonic crest cells in the ovary,
produces excessive quantities of androgens in
women
 Metabolism of Testosterone
• (97%) bound with plasma albumin or with a
beta globulin called sex hormone–binding
globulin and rest circulate in blood in free
form.
• Testosterone fixed to the tissues in target
organs is converted to Dihydrotestosterone
 Degradation and Excretion of
Testosterone
• The testosterone not fixed to the tissues is
converted by the liver into androsterone &
dehydroepiandrosterone
• Conjugated with glucuronides or sulfates in the
liver
• These substances are secreted in the bile by the
liver into the gut and ultimately excreted out of
the gut into feces
• Or excreted into the urine through the kidneys
 Production of Estrogen in the
Male
• Sertoli cells convert testosterone to
estradiol
• 80 % Estrogens in men are derived from
circulating androgens through
aromatization of testosterone and
Androstenedione
• aromatase enzyme in liver convert
testosterone to estradiol and
Androstenedione to estrone
Production of Estrogen in the Male
Plasma testosterone concentrations & sperm production at
different ages
 OBJECTIVES
• At the end of lecture students must be able to
– Explain functions of Testosterone
 FUNCTIONS OF TESTOSTERONE
• Functions of Testosterone During Fetal
Development
– SRY protein (TDF) initiates a cascade of gene
activations that cause the genital ridge cells to
differentiate into cells that secrete testosterone and
eventually become the testes
– Testes are stimulated by HCG from the placenta to
produce testosterone in 7th week of fetal life & 10 or
more weeks after birth
• Development of the male body characteristics
• Development of secondary sexual characteristics
• Descent of Testes
 Cryptorchidism
• Failure of a testis to descend from the abdomen
into the scrotum at or near the time of birth of a
fetus is called Cryptorchidism
– Testes are derived from the genital ridges in
the abdomen
– 3 weeks to 1 month before birth of the baby,
the testes normally descend through the
inguinal canals into the scrotum.
 Cryptorchidism (continued)
– Testes may not descent in few cases in IUL
– One or both testes may remain in the:
• Abdomen
• Inguinal canal
• Any where along the route of descent
– A testis that remains throughout life in the abdominal
cavity because of high temperature is not capable of
spermatogenesis.
• There is degeneration of tubular epithelium leaving
only the interstitial structures of the testes.
 Cryptorchidism (continued)
• Testosterone is important hormone secreted by the
fetal testes
• It causes the testes to descend into the scrotum
from the abdomen.
• Deficiency of Testosterone results from:
– Abnormally formed testes that are unable to
secrete enoaugh testosterone.
• The surgical operation is not successful in
these patietns
 Development of Adult Primary and Secondary
Sexual Characteristics
• Effect on the Distribution of Body Hair
• Causes Male Pattern of Baldness
• Causes Cracking of Voice
• Increases Thickness of the Skin
• Development of Acne
• Increases Protein Formation and Muscle Development
• Increases Bone Matrix & Calcium Retention
• Increases the Basal Metabolic Rate
• Increases Red Blood Cells
• Effect on Electrolyte and Water Balance
 Testosterone Secretion

• Responsible for initiation and maintenance

of body changes in puberty.
• Stimulate growth of muscles, larynx, and
bone growth until sealing of the epiphyseal
discs.
• Promote hemoglobin synthesis.
• Acts in paracrine fashion and is responsible
for spermatogenesis.
Hairline in children and adults
MECHANISM OF ACTION OF
TESTOSTERONE
CONGENITAL ADRENAL HYPERPLASIA
/ADRENOGENITAL SYNDROME
Congenital Adrenal Hyperplasia (CAH)

• Congenital adrenal hyperplasia refers to

autosomal recessive disease resulting from
mutations of genes responsible for production
of enzymes involved in steroidogenesis by the
adrenal glands
 Congenital Adrenal Hyperplasia

• Congenital defects in enzymes (21β-

hydroxylase & 11β-hydroxylase involved in
steroidogenesis resulting in less formation of
steroids, this results in increase ACTH
secretion
– Increase ACTH secretion results in adrenal
hyperplasia
 21β-hydroxylase (P450c21)
deficiency/Adrenogenital syndrome
• Mutation of 21β-hydroxylase gene results
in deficiency of this enzyme
• 90% of enzyme deficiency cases are due to
this
21β-hydroxylase (P450c21) deficiency
11β hydroxylase deficiency
/Adrenogenital syndrome
 Effects
• Deficiency of Mineralocorticoids
• Deficiency of Glucocorticoids
• Increase in sex hormones
• Increase in ACTH
• Results in Adrenal Gland hyperplasia
/Adrenogenital syndrome
• Increase in sex hormones (androgens) produces
virilization & Masculinizing effect
 Salt-Wasting CAH
• It is a the severe form of classic 21-
hydroxylase deficiency.
• In this type of CAH, the adrenal glands
make too little aldosterone, causing the
body to be unable to retain
enough sodium (salt). Too much sodium is
lost in urine (thus the name, "salt-wasting"
 Features In Females

• Masculinizing effects
• Ambiguous genitalia at birth
• Female develops virile characteristics such as
growth of a beard, deeper voice, baldness
• Masculine distribution of hair on the body and
the pubis
• Deposition of proteins in the skin & in the
muscles
• Poor feeding or vomiting
• Dehydration
• Electrolyte changes (abnormal levels
of sodium and potassium in the
blood)
• Arrhythmias
 In the pre-pubertal male

• Precocious puberty
• In adult male, the virilizing characteristics are
obscured by the normal virilizing characteristics of
the testosterone.
 Diagnosis

• High levels of 17alpha

hydroxyprogesterone in plasma
• Increased excretion of 17-ketosteroids
derived from androgens in the urine.
17alpha hydroxylase deficiency

– Deficiency of sex hormones

– Deficiency of cortisol
– Increase in production of Mineralocorticoids
– Increase retention of Na - Increase of BP
– Increased excretion of K
 OBJECTIVES:
• At the end of Lecture students should be able to:
– Discuss onset of puberty
– Explain the causes of abnormal Spermatogenesis and
Male infertility
– Describe control of male sexual functions
– Elaborate the causes of hypogonadism
 Onset of Puberty
• FSH and LH are high in newborn, falls to low levels in
few weeks after birth
• During childhood, the slightest secretion of any sex
steroid hormones exerts a strong inhibitory effect on
hypothalamic secretion of GnRH
• At the time of puberty, GnRH breaks through the
childhood inhibition
• Onset of puberty occurs by increased secretion of FSH
and LH
 Onset of Puberty

• Age of onset related to the amount of

body fat and physical activity in the
female
• Leptin secretion from adipocytes may be
required for puberty.
ABNORMAL SPERMATOGENESIS
AND MALE FERTILITY
 Causes of Male Infertility
• Low sperm count
• Cryptorchidism
• Excessive temperature of the testes
• Abnormal Sperm Morphology and Motility
• Antibodies that attack sperm
• Mumps Infection causing Bilateral Orchitis
of the testes
 Causes (cont…)

• Varicocele
• Congenital strictures in the genital ducts
• Tumors
• Hormone imbalances
• Defects of tubules that transport sperm.
 Low Sperm Count

• Quantity of semen is 3.5 milliliters (1-5ml)

• There are about 120 million sperm /ml
• Range is from 35 million to 200 million/ml
• When the number of sperm falls below 20
million/ml the person will be infertile.
Abnormal Sperm Morphology
 Abnormal Sperm Morphology
• Sperm abnormality is one of the factor that
results in infertility
• A man may has a normal number of sperms but
many or one half the sperm are found to be
abnormal physically
• Such as:
• having two heads
• abnormally shaped heads
• abnormal tails
 Abnormal Sperm Motility
• At other times, the sperm appear to be
structurally normal, but they are either entirely
nonmotile or relatively nonmotile.
• 40% of the sperm should be motile, or moving.
This can include non-progressive movement. At
least 32 %of the sperm should show progressive
motility
• Hence when the majority of the sperm are
morphologically abnormal or are nonmotile, the
person is likely to be infertile
 Abnormal Spermatogenesis and Male
Infertility
• The seminiferous tubular epithelium can be
damaged by a number of diseases and other
conditions, resulting in abnormal
spermatogenesis.
– Bilateral Orchitis of the testes resulting from mumps
– Congenital strictures in the genital ducts
– Excessive temperature of the testes
 Affect of Temperature on
Spermatogenesis
• Increasing the temperature of the testes
can prevent spermatogenesis by causing
degeneration of Spermatogonia and most
cells of the seminiferous tubules
 Cryptorchidism
• Failure of a testis to descend from the abdomen
into the scrotum at or near the time of birth of a
fetus is called Cryptorchidism
– Testes are derived from the genital ridges in
the abdomen
– 3 weeks to 1 month before birth of the baby,
the testes normally descend through the
inguinal canals into the scrotum.
 Cryptorchidism (continued)
– Testes may not descent in few cases in IUL
– One or both testes may remain in the:
• Abdomen
• Inguinal canal
• Any where along the route of descent
– A testis that remains throughout life in the abdominal
cavity because of high temperature is not capable of
spermatogenesis.
• There is degeneration of tubular epithelium leaving
only the interstitial structures of the testes.
 Cryptorchidism (continued)
• Testosterone is important hormone secreted by the
fetal testes
• It causes the testes to descend into the scrotum
from the abdomen.
• Deficiency of Testosterone results from:
– Abnormally formed testes that are unable to
secrete enoaugh testosterone.
• The surgical operation is not successful in
these patietns
CONTROL OF MALE SEXUAL
FUNCTIONS
 HORMONES FROM THE HYPOTHALAMUS AND
ANTERIOR PITUITARY GLAND

• GnRH and its effect in Increasing the secretion of LH & FSH

• Gonadotropic Hormones:
• Regulation of Testosterone production by LH
• Inhibition of Anterior Pituitary Secretion of LH and FSH by
Testosterone-Negative Feedback Control of Testosterone
Secretion
• Regulation of Spermatogenesis by FSH & Testosterone
• Role of Inhibin in negative feedback control of seminiferous
tubule activity
• Human chorionic gonadotropin secreted by
the placenta during pregnancy stimulates
testosterone secretion by the fetal testes
HYPOGONADISM IN THE MALE
 Hypogonadism in the Male
• Male Hypogonadism, also known as
testosterone deficiency, is a failure of the
testes to produce the testosterone, sperm, or
both.
• It can be due to a testicular disorder (primary
Hypogonadism) or the result of a disease
process involving the hypothalamus and
pituitary gland (Central Hypogonadism)
 Causes of Primary & Central
Hypogonadism
• Primary Hypogonadism:
– Klinefelter syndrome and Turner syndrome, Mumps
• Central Hypogonadism:
– Hypothalamic defects- Adiposogenital syndrome
– Pituitary defects include hypopituitarism and
pituitary hypoplasia
• Androgen insensitivity syndrome:
Hypogonadism resulting from the lack of
hormone response – receptor defect
 Hypogonadism in the Male
• When Testes of a male fetus are nonfunctional during fetal
life, male sexual characteristics do not develop properly
• Lose of testes before puberty – Eunuchism
– Infantile sexual characteristics
– Height is slightly greater than normal
– Bones are thin
– Muscles are weak
– Voice is childlike
– No loss of hair on the head
– Masculine hair distribution not present
• When Loss of testicular functions occurs after
puberty
– Some male secondary sexual characteristics
revert to those of a child and others remain of
adult masculine character
– Slight regression in the voice from the bass
quality
– Decrease in masculine hair production
– Decrease in thickness of bones
– Loss of the musculature
 Adiposogenital syndrome/
Fröhlich’s syndrome/
hypothalamic Eunuchism
• There is Hypogonadism due to genetic
inability of the hypothalamus to secrete GnRH
–Features of Eunuchism will be there
–It is associated with abnormality of the
feeding center of the hypothalamus,
causing uncontrolled food intake resulting in
obesity
Female Reproductive System
 Female Reproductive System
• Ovaries
• Fallopian tubes
• Extensions of fallopian tubes called
fimbriae partially cover each ovary
• Uterus
• Vagina
 Female Reproductive System
• Reproduction begins with the development of
ova in the ovaries.
• Ovaries:
– Contain large number of follicles which enclose
ova.
– At ovulation, secondary Oocyte is extruded
 OOGENESIS AND FOLLICULAR
DEVELOPMENT IN THE OVARIES
 OOGENESIS AND FOLLICULAR
DEVELOPMENT IN THE OVARIES
• Series of steps by which a developing egg (Oocyte)
differentiates into a mature egg (ovum) is called Oogenesis
• Primordial germ cells from the embryonic yolk sac migrate
into the ovarian cortex and become oogonia or primordial
ova
• Oogonia or primordial ovum collects around it a layer of
spindle cells from the ovarian stroma called granulosa cells
• The ovum surrounded by a single layer of granulosa cells is
called a primordial follicle
• Ovum is still immature and is called a primary Oocyte
• The oogonia in the embryonic ovary complete mitotic
replication and the first stage of meiosis by the fifth
month of fetal development
• The germ cell mitosis then ceases and no additional
Oocyte are formed
• At birth the ovary contains about 1 to 2 million primary
oocytes
• Oogenesis arrested in prophase of 1st meiotic division
(primary oocyte).
• Apoptosis occurs:
– 3 million primary oocytes at birth
 After Puberty
• First meiotic division of the
primary oocyte completed after
puberty
• Each oocyte divides into two i.e.
secondary oocyte and a small
first polar body
• Each of these cells contains 23
duplicated chromosomes
• The first polar body then
degenerates
 OVULATION
• Secondary oocyte is
ovulated it undergoes
second meiotic division
• After the sister chromatids
separate the meiosis II is
halted at metaphase II
stage until the ovum is
fertilized
 If the ovum is fertilized
• If the ovum is fertilized the final
step in meiosis occurs and the
sister chromatids in the ovum go
to separate cells.
• Half of the sister chromatids
remain in the fertilized ovum
and the other half in a second
polar body
• Second polar body then
disintegrates
 OBJECTIVES:
• At the end of lecture students should be
able to:
–Discuss female hormonal system
–Explain ovarian cycle & Endometrial
cycle
FEMALE HORMONAL SYSTEM
• At birth
– each ovum is surrounded by a single layer of
granulosa cells & is called a Primordial Follicle
• In childhood
– granulosa cells provide nourishment for the ovum
and secrete an oocyte maturation inhibiting factor
(OMIF) that keeps the ovum suspended in its
primordial state in the prophase stage of meiotic
division
• After puberty
– FSH and LH are secreted in significant quantities &
the ovaries begin to grow
 FEMALE HORMONAL SYSTEM

• Gonadotropin-releasing hormone
(GnRH)
• Follicle stimulating hormone (FSH) and
luteinizing hormone (LH)
• Ovarian hormones -estrogen and
progesterone
Female Monthly Sexual Cycle
• Monthly rhythmical changes in the rates
of secretion of the female hormones and
corresponding physical changes in the
ovaries & uterus is called the female
monthly sexual cycle
 GONADOTROPIC HORMONES AND THEIR
EFFECTS ON THE OVARIES
• Puberty
– At 9 to 12 years of age, the pituitary begins to
secrete progressively more FSH and LH under
the influence of GnRH
• Menarche
– The age of onset of first normal monthly sexual
(menstrual) cycles (11 and 15 years) is called
cycle menarche
 Plasma concentrations of the Gonadotropins and
ovarian hormones during the normal female sexual cycle
Importance of Female sexual cycle

• Only a single ovum is normally released

from the ovaries each month
• The endometrium is prepared in advance
for implantation of the fertilized ovum at
the required time of the month.
 Summary of ovarian cycle
• Each month following the menarche at 12 years of age,
several follicles begin to develop into Graafian follicles.
• One of the Graafian follicles becomes dominant, grows
very large, produces a bulge at the ovarian surface and
finally ovulates. This is the follicular phase of the
menstrual cycle and is controlled by FSH
• FSH release is in turn controlled by GnRH from the
hypothalamus
• Under FSH stimulation the growing follicle matures and
secretes increasing amounts of estrogen
 Summary of ovarian cycle
• At 14th day of the cycle estrogen triggers a surge of LH
secretion from the anterior pituitary (a positive
feedback effect), which results in the release of the
ovum.
• The high LH concentration also promotes the
formation of a corpus luteum and secretion of
progesterone
• Progesterone from the corpus luteum prepare the
uterus for possible pregnancy.
• If pregnancy does not occur, the corpus luteum
degenerates about 12 days after ovulation and
progesterone levels fall.
 Ovarian Cycle
• FSH & LH causes activation of the cAMP
second messenger system which activates
protein kinase which in turn causes
phosphorylation of key enzymes that
stimulate estrogen & progesterone
synthesis
 Ovarian Cycle
• Follicular phase
• Ovulation
• The Luteal phase
 FOLLICULAR PHASE OF
THE OVARIAN CYCLE
• Follicular phase is a period of follicular growth in
the ovary, variable in length, lasts from 10 days
to 3 weeks
– The first stage of follicular growth is moderate
enlargement of the ovum
– That stage is followed by growth of additional
layers of granulosa cells in some of the
follicles. These follicles are known as primary
follicles.
 Development of Antral Follicles
• During the first few days of each monthly female sexual
cycle FSH increases slightly greater than that of LH
• FSH, cause accelerated growth of 6 to 12 primary
follicles each month.
• The initial effect is rapid proliferation of the granulosa
cells, giving rise to many layers of cells.
• Spindle shaped cells derived from the interstitium of
ovary collect in several layers outside the granulosa
cells, forming a second mass of cells called the THECA
CELLS
 THECA CELLS
• The theca is divided into two layers
• Theca Interna
– The cells take on epithelioid characteristics and
develop the ability to secrete estrogen and
progesterone
• Theca externa
– develops into a highly vascular connective tissue
capsule that becomes the capsule of the developing
follicle
Stages of follicular growth in the ovary
• After the early growth of follicles the granulosa
cells secretes a follicular fluid that causes an
antrum to appear within the mass of granulosa
cells that contains a high concentration of
estrogen
• The primary source of estrogen is the granulosa
cells
• The early growth of the primary follicle up to the
Antral stage is stimulated mainly by FSH alone
• Theca interna secrete androgens that are
aromatized by the granulosa cells (FSH activates
aromatase enzyme) to estrogen
 Formation of vesicular follicles
• Greatly accelerated growth forms vesicular follicles by the
following mechanisms:
– Estrogen increases number of FSH receptors on
granulosa cells making the granulosa cells more sensitive
to FSH
– FSH and Estrogens combine to promote LH receptors on
the granulosa cells and causes LH stimulation to occur in
addition to FSH stimulation and causes more rapid
increase in follicular secretion
– LH & Estrogens cause proliferation of theca cells and
increase their secretion as well
 Only One Follicle Fully Matures Each Month,
and the Remainder Undergo Artesia
• After a week of growth before ovulation occurs—one of the
follicles outgrows, and the remaining 5-11 developing
follicles involute & become atretic
• The large amounts of estrogen from the most rapidly
growing follicle depress further FSH secretion blocking
further growth of the less well-developed follicles.
• Largest follicle continues to grow because of its intrinsic
positive feedback effects (estrogen stimulates granulosa
cells which produces more estrogen)
• The single follicle reaches a diameter of 1 to 1.5
centimeters at the time of ovulation and is called the
mature follicle.
 Plasma concentrations of the Gonadotropins and
ovarian hormones during the normal female sexual cycle
• FSH stimulates the ovarian follicle, causing an
egg to grow. It also triggers the production of
estrogen in the follicle. The rise in estrogen
tells your pituitary gland to stop producing
FSH and to start making more LH. The shift
to LH causes the egg to be released from the
ovary
 Ovulation
• About 14th day of the cycle, the distended follicle
ruptures, and the ovum is extruded, this is called
ovulation
• Outer wall of the follicle swells rapidly, and a small
area in the center (stigma) of the follicular capsule
protrudes & fluid begins to ooze through it
• Later on the stigma ruptures widely and more
viscous fluid with ovum move outward. Ovum is
surrounded by a mass of granulosa cells, called the
Corona Radiata
 A Surge of Luteinizing Hormone Is
Necessary for Ovulation
• LH increases 2 days before ovulation & peak levels
reach 16 hours before ovulation
• FSH also increases at the same time
• FSH and LH cause rapid swelling of the follicle
before ovulation
• LH acts on the granulosa & theca cells, converting
them mainly to progesterone secreting cells
• Secretion of estrogen begins to fall 1 day before
ovulation, while progesterone secretion increases
 Plasma concentrations of the Gonadotropins and
ovarian hormones during the normal female sexual cycle
 It is in this environment of:

• Rapid growth of the follicle

• Diminishing estrogen secretion after a prolonged
phase of excessive estrogen secretion
• increase secretion of progesterone
• ovulation occurs.
• Without the initial preovulatory LH surge
ovulation will not take place.
Interaction of follicular theca and granulosa
cells for production of estrogens
 LH causes rapid secretion of progesterone
• Two events occur
• Theca Externa begins to release proteolytic enzymes
(collagenase) from lysosomes, dissolution of collagen
in CT holding follicular cells together in the capsular
wall occurs & wall weakens, resulting in further
swelling of the entire follicle and degeneration of the
stigma
• Rapid Growth of new blood vessels into the follicle
wall, inflammatory reaction due to break down
products of collagen- attracts WBC-prostaglandins
(vasodilation) are secreted in the follicular tissues
Initiation of Ovulation
 LUTEAL PHASE
OF THE OVARIAN CYCLE
• Process of luteinization
–First few hrs after expulsion of the ovum,
remaining granulosa and theca interna cells
enlarge in diameter, become filled with lipid
inclusions (yellowish appearance) called
lutein cells and the total mass of cells
together is called the corpus luteum
 Luteal Phase
• LH stimulates formation of the empty follicle into
corpus luteum.
• Corpus luteum secretes:
– Progesterone
– Estrogen
• Estrogen mainly and progesterone have Negative
feedback on LH and FSH.
• Inhibin: suppress FSH.
Interaction of follicular theca and granulosa
cells for production of estrogens
 Fate of the Follicle that Ruptures
• The follicle that ruptures at the time of ovulation
promptly fills with blood, forming what is
sometimes called a Corpus Hemorrhagicum
• The granulosa and theca cells of the follicle lining
promptly begin to proliferate, and the clotted
blood is rapidly replaced with yellowish, lipid rich
Luteal cells, forming the corpus luteum
• This initiates the Luteal phase of the menstrual
cycle, during which the Luteal cells secrete
estrogen and progesterone
Formation of The Corpus Luteum
 Corpus Luteum

• Granulosa cells in the corpus luteum develop

extensive SER that form large amounts of the
estrogen & progesterone
• Theca cells form androgens Androstenedione
and testosterone
• Most of these hormones are converted by
aromatase in the granulosa cells into estrogens
• The corpus luteum grows to the size of 1.5 cm
in 7 to 8 days after ovulation
 Fate of the Follicle that Ruptures
• Growth of the Corpus Luteum depends on its
developing an adequate blood supply, and there is
evidence that vascular endothelial growth factor
(VEGF) is essential for this process.
• If pregnancy occurs, the corpus luteum persists,
there are no more periods until after delivery.
• If pregnancy does not occur, the corpus luteum
begins to degenerate (24-26th day of the cycle)
and is eventually replaced by scar tissue, forming a
Corpus Albicans
Secretion by the Corpus Luteum: An Additional
Function of Luteinizing Hormone
• Secrete large amounts of both progesterone,
estrogen and inhibin