Reproduction (Dr. B.

Vanderhyden)
1. Describe gender determination during embryogenesis
1. Identify the determinants of genetic, gonadal, and phenotypic sex

physiologizi
ng.blogspot.
com

Genetic sex
• Depends on the combination of sex chromosomes at the time of
conception
 XX or XY
• Determines gonadal sex
 Whether testes or ovaries develop
Gonadal Sex
• Presence or absence of a Y chromosome determines gonadal
differentiation
 For the first money and a half of gestation, all embryos have
potential to differentiate along either male or female lines
 Gonadal specificity appears during the 7th week of intrauterine
(inside uterine) life under the influence of sex-determining region
of the Y chromosome (SRY)
 The single gene responsible for sex determination
 SRY triggers a chain of reactions that leads to physical
development of a male, as SRY “masculinize” the gonads
by stimulating H-Y Antigen
 H-Y antigen is only found in males
 H-Y antigen is a specific PM protein found only in
males that directs differentiation of the gonads into
testes
 Genetic females lack the SRY gene and consequently do
not produce H-Y antigen
 Their gonadal cells never receive a signal for
testicular formation
 Therefore, by 9th week, undifferentiated gonadal
tissue begin developing into ovaries
Phenotypic Sex
• Depends on the genetically determined gonadal sex
“Sexual differentiation”
: embryonic development of the external genitalia and reproductive tract
along mle/female
• Differentiation into male-type reproductive ststem is induced by
androgens
o Androgen is a masculinizing hormone secreted by the
developing testes
Ex) testosterone
 Absence of androgen results in development of female-
type reproductive system
  By 10th ~12th weeks of gestation, sexes can be
distinguished by anatomic appearance of external
genitalia

Sexual differentiation of the reproductive tract

• Male and female external genitalia develop from the same embryonic
tissue
• Male and female reproductive tracts are not developed from the same
undifferentiated embryonic tissue
 Two primary duct systems developed in all embryos
 Wolffian ducts
 Mullerian ducts

• In males,
 Reproductive tract develops from wolffian ducts
 Mullerian ducts degenerate
• In females,
 Reproductive tract develops from mullerian ducts
 Wolffian ducts regress
• Since both duct systems are present before sexual differentiation
occurs, early embryo has potential to develop eother male or female
reproductive tract

Development of reproductive tract

: Determined by the presence or absence of two hormones secreted by
fetal testes: testosterone and Mullerian inhibiting factor

Males:
o Testosterone
• Induces development of the wolffian ducts into the male reproductive
tract
• testosterone is then converted to Dihydrotestosterone (DHT) to be
responsible for differentiating the external genitalia into penis and
scrotum
 o Mullerian inhibiting factor
• Causes regression of the Mullerian ducts

Females:
• Absence of testosterone causes wolffian ducts to degrade
• Allows Mullerian ducts to develop into the female reproductive tract and
external genitalia to differentiate into clitoris and labia

2. List the three major cell types of a newly formed ovary and testis

three major cell types of a newly formed ovary are:

1. Oogonia
• These are immature egg cells that are produced in large numbers
during fetal development.
• eventually undergo meiosis to form primary oocytes.

2. Granulose
3. theca

Three major cell types of a newly formed testis are:

- Spermatogonia
• These are immature sperm cells that are produced in large numbers
during fetal development.
• eventually undergo meiosis to form sperm cells.
- Sertoli cells
• These are cells that support and nourish the developing sperm cells.
• produce hormones such as testosterone and inhibin.
- Leydig cells
• These are cells that produce testosterone, the male sex hormone which
plays a key role in male sexual development.
3. Describe how hormones regulate phenotypic sex differentiation

2. Describe the anatomy of the male reproductive system

- primary role of the male reproductive system is to produce and deliver

sperm to fertilize an egg in the female.
 These sperm are produced outside the body cavity by the testicles,
which are located in the scrotum.
• The scrotum protects and supports the male reproductive organs
that are located outside the body cavity.
o include the testicles, epididymis, and the vas deferens.

- The testicles produce about three hundred million sperm each day.
However, this is possible only if the temperature of the testicle is 93.2
degrees Fahrenheit.
 The scrotum maintains this temperature by adjusting how closely it
holds the testicles to the body.
- The interior of each testicle consists of multiple lobules containing two or
three seminiferous tubules.
  It is within these tubules that sperm formation begins.
 The sperm moves out of the tubules into the epididymis and then
into the vas deferens.
 The vas deferens carry the sperm upward into the body cavity.
 After the sperm leaves the vas deferens through the ejaculatory
ducts, they pass the openings of the seminal vesicles.
- The seminal vesicles, which are located near the base of the ejaculatory
ducts, secrete a thick, yellow substance to nourish the sperm.
 This secretion forms 60 percent of the volume of the semen.
- Semen is the sperm-containing fluid that is ejaculated at the climax of male
sexual excitement.
 From here, the semen travels into the eight-inch-long urethra, which
transports both urine and semen, but not at the same time.
 At first, the urethra is surrounded by the prostate gland, and then it is
surrounded and protected externally by the penis that is relaxed
except during sexual excitement.
 During sexual excitement, the penis stiffens and enlarges so it can
deliver the sperm into the female vagina.
 During the expelling of the semen, which is known as ejaculation,
the prostate gland secretes a thick, alkaline fluid that increases the
ability of the sperm to move in the semen.
- Located just below the prostate gland are the bulbourethral glands.
 These glands open into the urethra, and, during sexual arousal, they
secrete the pre-ejaculate fluid that flushes out any residual urine
from the urethra.
 It also lubricates the urethra to help the sperm pass through.
- When the male ejaculates into the vagina of the female, the sperm must
travel upward through the uterus to fertilize the egg in the Fallopian tube.

Internal sex organs

• Testis
• Main male reproductive organ
2 main functions
 Produce male gametes – sperms
 Produce testosterone
• Seminiferous tubules
• Location: inside lobules (sections inside the testis divided by septage)
• Highly coiled tube-like structure
 Central lumen and outer wall
 Wall of seminiferous tubules contain three types of cells
 Leydig cells
 germ cell
 Sertoli cells

• Epididymis
• Connects testis to vas deferens
• Immature sperms produced in the seminiferous tubules transport to the
epididymis via efferent ducts
• Three parts
 Head, body, tail
 Immature sperms travel towards the tail of the epididymis and go
through the process of maturation
 During maturation, immature becomes mature and gain
properties such as motility and fertility

• Vas deferens
• Connects epididymis to ejaculatory duct

• Seminal vesicle
• Small secretory gland connected to vas deferens
• Produces seminal fluid
 that mixes with sperms and forms semen
• alkaline
 prolongs the survival of sperms in acidic vagina
• joins with vas deferens to form the ejaculatory ducts

• Prostate gland
• Walnut sized organ below the bladder and surrounds urethra
• Secretes alkaline fluid that forms 30% of total semen volume
• Improves survival & motility of the sperms
1. Describe the gross and microscopic anatomy of the testes

- Testes perform dual function of producing sperm and secreting

testosterone
o Spermatogenesis + steroidogenesis
- 80% of testicular mass consists of seminiferous tubule
o Place where spermatogenesis and meiosis take place
- Leydig cells, the endocrine cells that produce testosterone, lie in the
connective tissue between the seminiferous tubule
o Production of testosterone in regulated by pituitary gland’s secretion
of luteinizing hormone

2. Describe the pathway followed by sperm from the testis to the exterior of
the body

i. Sperm produced in the testes through spermatogenesis

ii. Sperm move through to epididymis, back of testes responsible for storage,
maturation and transport of sperm
iii. Sperm then travels through the vas deferens, a tube that runs from
epididymis to the base of prostate gland.
 1. Vas deferens is responsible for propelling the sperm towards the
exterior of the body through contractions
iv. At ejaculation, sperm moves into the urethra

In summary,
Testes  epididymis  vas deferens  urethra

3. Localize and describe the structure of the male reproductive accessory

glands

 Seminal vesicle
 Two small sac like glands located behind the bladder, near the base of
the urinary tract
 Secretes thick viscous fluid that makes up 60~70% of semen
 Contains fructose, which provides energy for sperm
 Washes the sperm into the urethra and dilutes the thick mass of
sperm to enable them to become mobile
• Secretes prostaglandins
 Stimulates contraction of reproductive tracts to stimulate motility
to help trasnport the sperm
 Helps to transport sperm from their storage site int eh male to the
site of fertilization in the female oviduct
• Supply fructose to nourish the ejaculated spem

 Prostate gland
o Large single gland that completely surrounds ejaculatory ducts and
urethra
o Secretes thin milky product that makes up 20~30% of the semen
 Contains enzymes to help protect and nourish the sperm
o Secretes alkaline fluid to neutralize the acidic vagina secretions

 Bulbourethral gland (Cowper’s gland)

o Below the prostate gland
o Secretes clear, mucus-like fluid that lubricates the urethra before
ejaculation
  This fluid lubricates urethra for spermatozoa

4. Describe the structural organization of the penis as a copulatory organ

External sex organs

• Penis
o Common pathway for urine and semen
o Made of root, body and gland

o Structure of the root of penis

 Attaches penis to the body
o Structure of the body of the penis
 Consists of three columns of erectile tissues
 2 corpora cavernosa
 Columns of erectile tissue spaces or caverns
 Gets filled with blood
 Contains deep arteries
 1 corpus spongiosum
 Columns of spongy tissue
 Urethra passes through this tissue
o Structure of gland of the penis
 Enlarged corpus spongiosum at one end
 Covered with foreskin

• Scrotum
o Pouch like structure of skin
Two main functions
• Protects the testis
• Maintains 2~3*C temp lower than the body temperature
 Important for spermatogenesis

5. Describe sexual response in male vs female

Male sexual response

 1. erection of penis
- mechanoreceptor activation or sensory input causes increased
parasympathetic and decreased sympathetic input
- results in vasodilation caused by nitric oxide release from autonomic neurons
→ arterial smooth muscle relaxation
- vasocongestion in the corpora cavernosa
- enhanced by passive compression of the veins

2. emission
- sympathetic contraction of smooth muscle surrounding vas deferens and
glands to move sperm from epididymis through vas deferens into urethra

3. expulsion (ejaculation)
- sympathetic spinal level reflex
- smooth muscle contraction of tubular system, and skeletal muscle
contractions at base of the penis
- release of ~3 ml semen containing ~300 million sperm
- followed by latent period (minutes to hours) during which a second erection is
not possible

Mechanism of erection of the penis

Female Sexual Response

- general vasocongestion of vaginal epithelia and clitoris
- increased vaginal secretion of mucus made less viscous at the time of
ovulation
- muscular contractions of uterus and vagina to increase sperm transport to
Fallopian tubes
- uterine motility
o increased by estradiol, decreased by progesterone
- sex drive somewhat dependent on androgen production (adrenals and
ovaries)

Four phases of sexual response:

I. excitement
o erection, increased blood pressure and heart rate, increased skeletal
muscle tone, vaginal secretions
II. plateau - emission
III. orgasm - ejaculation, vaginal and uterine contractions
IV. resolution - return to normal

6. List the structural components of a spermatozoa and describe their

function

4 Parts: head, acrosome, midpiece, tail

 Head
- Consists primarily of the nucleus
o Contains sperm’s complement of genetic information

 Acrosome
- Enzyme filled vesicles that caps the tip of the head
o Used as an “enzymatic drill” for penetrating the ovum
- Formed by aggregation of vesicles produced by the endoplasmic
reticulum/Golgi complex before these organelles are discarded

 Midpiece
 - Movement of the tail is powered by energy generated by the mitochondria
concentrated within the midpiece of the sperm

 Tail
- Provides motility

6. Describe the composition of semen

 fluid produced by the seminal vesicles – 60~70%

 prostate gland – 20~30%
 testicles and epididymis – 5%
 Bulbourethral and urethral glands – 2%

1. Fructose – energy for sperm (seminal vesicles)

2. Bicarbonate buffers – to buffer acidity of vaginal secretion (prostate)
3. prostaglandins - stimulate sperm motility and contractions of female
reproductive tract (seminal vesicles)
4. clotting factors - for retention of sperm within the vagina (fibrinogen
from seminal vesicles, and clotting enzymes and fibrinolysin from
prostate

3. Describe the regulation of male reproductive function system

1. Distinguish steroid hormones (both structurally and functionally) from
amino acid-based hormones

Steroid hormones
- derived from cholesterol
- include testosterone, estrogen, progesterone, and cortisol
- lipophilic
o soluble in lipids
o able to diffuse through cell membranes to reach their target cell
- hydrophobic,
 o insoluble in water
o binds to intracellular receptor and affects the transcription of target
genes
- long-lasting effects
o exert their actions by altering the transcription of target genes
- involved in many physiological processes such as growth, development,
and metabolism.

Amino acid-based hormones

- derived from amino acids,
o epinephrine, norepinephrine, thyroxine, and insulin
- hydrophilic
o soluble in water and unable to diffuse through cell membranes
- bind to receptors on the cell surface or intracellularly and affect the activity
of enzymes or the opening or closing of ion channels
- rapid effects
o exert their actions by altering the activity of enzymes or the opening
or closing of ion channels
- involved in in many physiological processes such as metabolism,
cardiovascular function and immune function

2. List the actions of androgen in the body

Sex differentiation
- Growth and development of Wolffian ducts (internal genitalia)
- Development of penis and scrotum (external genitalia)
- Descent of the testes into the scrotum
- Differentiation of the brain
o establishes male pattern of sexual behaviour after puberty

Spermatogenesis
- At puberty: completion of meiotic division and early maturation of
spermatids
- After puberty: maintenance of spermatogenesis
 Secondary sex characteristics
- Growth and maintenance of accessory sexual organs
- Growth of penis
- Growth of facial, axillary, chest and pubic hair, male pattern baldness
- Body growth

Anabolic effects
- Protein synthesis and muscle growth
- Growth of bones and closure of epiphyses at ends of long bones
- Growth of other organs (including larynx)
- Erythropoiesis
o stimulates erythropoietin secretion by kidneys

Behavioural effects
- Aggression (at least in animals)
- Increased libido

3. Describe the hypothalamic and pituitary regulation of steroidogenesis in

the male

- hypothalamus, produces gonadotropin-releasing hormone (GnRH)

o responsible for triggering the release of luteinizing hormone (LH)
and follicle-stimulating hormone (FSH) from the anterior pituitary
gland.
 These hormones travel to testes where they stimulate the
Leydig cells to produce testosterone
o LH and FSH are gonadotropins
 Gonadotropins
: hormones that regulate the functions of the gonads (testes)

- LH stimulates the Leydig cells in the testes to produce testosterone.

o Acts in negative feedback fashion to inhibit LH secretion in two ways
  Decrease GnRH release by acting on the hypothalamus,
which indirectly decreases both LH and FSH release
 Reduce the responsiveness of the LH secretory cells to GnRH

- FSH stimulates the Sertoli cells in the seminiferous tubule in testes to

support spermatogenesis.
o FSH regulates the production and maturation of sperm cells
o helps to maintain the structural integrity of the seminiferous tubules
in the testes where spermatogenesis occurs

- hypothalamus monitors the levels of testosterone and responds by

adjusting the release of GnRH accordingly.
o If the levels of testosterone are too high, the hypothalamus reduces
the release of GnRH, which in turn reduces the release of LH and
FSH, resulting in a decrease in testosterone production.
o If the levels of testosterone are too low, the hypothalamus increases
the release of GnRH, which in turn increases the release of LH and
FSH, resulting in an increase in testosterone production

4. Outline the main steps in spermatogenesis, as a progression through

meiosis
 Spermatogenesis
- Process by which sperm cells are produced in the testes
o More specifically, in the walls of seminiferous tubules inside
testis
- 4 sperm cells formed from each primary spermatocyte that enters
meiosis
- Takes 64 days for development from a spermatogonium to a mature
sperm
- ~30 million sperm / day

Stages of spermatogenesis
A. Mitotic proliferation
B. Meiosis
C. Packaging

A. Mitotic proliferation
- Spermatogonium located in the outermost later of the seminiferous
tubule divide mitotically
o All cells bearing full 46 chromosomes identical to parent cell
- Following mitotic division of a spermatogonium, one of the daughter
cells remains at the outer edge of the tubule as undifferentiated
spermatogonium
o Maintains the germ-cell-line
 - The other daughter cell moves toward the lumen through various
developmental stages to form sperm, which is released into the
lumen
- Sperm forming daughter cell divides mitotically twice more to form
four identical primary spermatocytes
o Following the last division, primary spermatocytes enter rest
phase – chromones duplicates and prepares for meiotic
division

B. Meiosis
- Each primary spermatocyte (diploid number of 46 doubled
chromosomes) forms two secondary spermatocytes (each with
haploid number of 23 doubled chromosomes) during the first meiotic
division to form four spermatids (23 single chromosomes)
- no further division after this stage
- each spermatid is remodelled into a single spermatozoon
o human can theoretically produce 16 spermatozoa each time a
spermatogonium initiates this process

C. Packaging
- Process of spermiogenesis

I. Takes place inside the seminiferous tubules

II. Diploid spermatogonia located near the outer edge of the tubule divide via
mitosis to form primary spermatocytes
III. First mitotic division produces secondary spermatocytes with a haploid
number of duplicated chromosomes
IV. Second mitotic division produces spermatids
a. Each with 23 single chromosomes
b. Maturation of spermatids produce sperm
V. Sertoli cells, the only other type of cells in the seminiferous tubule,
provides the forerunners of the sperms with nourishment and molecular
signal
VI. Mature sperm consists of a head with an enzyme containing cap, a mid
piece with mitochondria to provide energy for locomotion, and a whip like
tail with a core of microtubules

5. Describe spermiogenesis

- The final stage of spermatogenesis

- Process by which the spermatids mature into sperm cells
o Occurs in epididymis
o Motility is acquired in the epididymis.
- Spermatogenesis: process of producing sperm cells
- Spermiogenesis: process of maturing of sperm cells

• most of cytoplasm is discarded

 sperm head = 2-3 μm in diameter, 5 μm long, nucleus + plasma
membrane
• develops a flagellum or tail
 for locomotion, 3-4 mm/min
• develops a midpiece of mitochondria
 powers motility by providing ATP
• develops an acrosome
 bag of enzymes on the head beneath plasma membrane enzymes =
hyaluronidase, proteases

q spermatids undergo a series of changes that result in the formation of fully

mature sperm cells. This process includes…
o formation of a tail
o development of the acrosome (a cap-like structure that contains enzymes
necessary for fertilization)
o formation of the midpiece, which contains the sperm's energy-producing
mitochondria

6. Explain why Y bearing male producing sperm cannot develop and

survive without exchanging cytoplasm of developing germ cells by
cytoplasmic bridges?

• Until sperm maturation is complete, developing germ cells arising from single
primary spermatocytes remain joined by cytoplasmic bridges.
 These connections permit the four developing sperm to exchange
cytoplasm
 This linkage is important because…
 X chromosome contains genes that code for cell products
essential for sperm development (ex. SRY in male)
 During meiosis in sperm formation, half the sperm receive X and other
half a Y chromosome
 If not for sharing of cytoplasm, not all haploid cells would be
provided with the products coded for by X chromosomes until
sperm development is complete, thus the reason why Y-bearing
male producing sperm would not develop and survive
 During oogenesis, every ovum receives an X chromosome
 Because separation of the XX sex chromosome pairs yield only X
chromosome

Genetic variability of gametes

1) crossing-over
2) random distribution of maternal and paternal chromatid pairs

7. Define blood-testis barrier and list the functions of Sertoli and Leydig
cells in supporting spermatogenesis

Blood-testis barrier
• Specialized structure that separates the blood vessels from the seminiferous
tubules in the testes, where spermatogenesis occurs
• Formed by Sertoli cells
• Tight junction forms a physical and functional barrier that prevents the entry of
blood-borne substances and immune cells into the seminiferous tubules and
protect the developing sperm cells
 Prevents blood borne substances from passing between the cells to
gain entry to the lumen of the seminiferous tubule
• Prevents the anti-body producing cells in the ECF from reaching the tubular
sperm factory
 Prevents formation of antibodies against highly differentiated
spermatoza
• Because developing sperm cells do not have direct access to blood-borne
nutrients, the Sertoli cells provide nourishment

Sertoli cells
• Specialized support cells that line the walls of the seminiferous tubules
• Forms a blood-testes barrier from tight junctions between adjacent Sertoli
cells
• Nutritional support
 Provides nutrients and energy to the developing sperm cells through
‘spermatogenic nourishment’
 Involves transfer of nutrients (glucose, amino aicds)
• Physical support
• Immune protection
 Prevents the entry of harmful substances and immune cells into the
seminiferous tubule
• Hormonal regulation
 Sertoli cells respond to FSH by producing androgens binding proteins
(ABP)
 ABP binds to testosterone and transports it to the developing
sperm cells
 Maintains appropriate levels of testosterone for spermatogenesis
• Important phagocytic function
 Engulfs the cytoplasm extruded from the spermatids during remodelling
and destroy defective germ cells that fail to successfully complete all
stages of spermatogenesis
• Secretes into the lumen seminiferous tubule fluid
 Flushes the release sperm from the tubule into the epididymis for
storage and further processing
• Secretes Androgen-Binding Protein (ABP)
 ABP binds androgens- specifically, testosterone
 Maintains a high level of testosterone within seminiferous tubule
lumen
 o Testosterone is 100 times more concentrated in
seminiferous tubule than in blood
 Essential for sustaining sperm production
 ABP retains testosterone within the lumen
• Site of action for control of spermatogenesis by both testosterone and follicle-
stimulating hormone (FSH)
 Production of FSH is associated with the production of ABP
 Production of inhibin (hormone) acts in negative feedback fashion to
regulate FSH regulation
 Inhibin acts directly on the anterior pituitary to inhibit FSH
secretion
o This feedback inhibition of FSH appropriate because FSH
stimulates spermatogenesis by acting on Sertoli cellls

Functions of Sertoli cells

1) nurture developing sperm
2) maintain blood-testis barrier
3) produce androgen-binding protein (ABP)
4) respond to FSH and testosterone to promote spermatogenesis
5) produce inhibin
6) produce seminiferous tubular fluid
7) remove damaged germ cells by phagocytosis

Leydig Cells
• Located in the connective tissue between seminiferous tubules
• Responsible for the production of testosterone
 Through the process of steroidogenesis
 Regulated by the pituitary gland’s secretion of luteinizing hormone

8. Describe the functional contributions of the epididymis and the

accessory organs to the production of semen

Epididymis
• After sperm have been produced in the seminiferous tubules, they are swept
into the epididymis due to the pressure created by continual secretion of
tubular fluid from Sertoli cells
• Spermatozoa entering the epididymis is non-motile
 Due to low pH in epididymis and vas deferens

Functions
• Serves as sperm’s exit route from the testis
 Sperms matures during the passage through epididymis
 Gains capabilities to move and fertilize
o Sperm’s capacity to fertilize is enhanced by exposure to
secretion of female reproductive tract
 “capacitation”
 Maturation is stimulated by the testosterone retained within the tubular
fluid bound to androgen-binding protein

Duct deferens
• Serves as an important site for sperm storage
• Tightly packed sperms are relatively inactive and their metabolic needs are
low
• They can be stored for many days without nutrient blood supply and are
nourished only by simple sugats present in tubular secretion

Capacitation
:an undefined chemical process that occurs primarily in the female reproductive
tract
1) necessary for fertilization
2) changes in the plasma membrane of the spermatozoa
3) accelerated motility of spermatozoa

4. Describe the anatomy of the female reproductive system

- The major structures of the female reproductive system

 - two ovaries, two fallopian tubes, the uterus, and the vagina.
- A normal female is capable of reproducing from the onset of menstruation --
during puberty, until the end of menopause.
- The female is fertile and able to become pregnant approximately during the
13th and 14th days of each menstrual cycle.
- The total number of eggs a woman will produce in her lifetime are present in
her ovaries when she is born. (~4 million oocytes at birth, ~400,000 remain at
puberty, ~400 ovulate)
- Each month, at the beginning of a menstrual cycle, the pituitary gland secrets
the follicle-stimulating hormone, which is commonly known as FSH.
- This hormone stimulates one egg to mature within an ovary.
- A maturing egg is surrounded by a graafian follicle.
- On the 13th or 14th day of the menstrual cycle, the graafian follicle ruptures
and releases the mature egg from the ovary.
- Because the fallopian tube is not attached to the ovary, the finger like fimbriae
must catch the egg and guide it into the fallopian tube.
- After the release of the egg, the graafian follicle changes and becomes the
corpus luteum, which secretes the hormone progesterone, in preparation of
the lining of the uterus to support a pregnancy.
- If the egg is not fertilized, the corpus luteum dies and the progesterone
secretion ceases.
- The menstrual cycle is then completed with a menstrual period.
- If the egg is fertilized as it travels down the fallopian tube, the corpus luteum
continues to produce progesterone.
- The fertilized egg moves into the uterus, where it is implanted.
- The placenta forms and, for the duration of the pregnancy, it secretes the
progesterone required to maintain the pregnancy.
- Throughout the 40 weeks of the pregnancy, necessary nutrients are supplied,
and waste products are removed by the placenta and the umbilical cord.
- When it is time for the baby to be born, the pituitary gland secretes the
hormone oxytocin.
- This hormone stimulates the labor contractions that result in the birth of the
child.
- After the infant has been delivered, the final stage is the delivery of the
placenta, as the afterbirth.
 1. Describe the gross and microscopic anatomy of the ovaries

The ovaries are the primary female reproductive organs, performing the dual
function of producing ova (oogenesis) and secreting estrogen and progesterone.
• These hormones act together to promote fertilization of the ovum and to
prepare the female reproductive system for pregnancy.
o Estrogen in the female governs many functions similar to those carried
out by testosterone in the male,
 maturation and maintenance of the entire female reproductive
system
 establishment of female secondary sexual characteristics.
• In general, the actions of estrogen are important to preconception events.
o Estrogen is essential for…
 ova maturation and release
 development of physical characteristics that are sexually
attractive to males
 transport of sperm from the vagina to the site of fertilization in the
oviduct.
 contributes to breast development in anticipation of lactation.
o Progesterone is essential for…
 preparing a suitable environment for nourishing a developing
embryo/fetus
 contributing to the breasts’ ability to produce milk.

Functions of ovaries
- production of germ cells (oogenesis
- oogenesis
- steroidogenesis (steroid hormone prduction

2. Describe the structural components of the female reproductive tract

3. Describe the gross and microscopic anatomy of the uterus

4. Describe the pathway followed by an embryo

I.

5. Describe the regulation of female reproductive function

1. Describe ovarian steroidogenesis as a compartmentalized process (two

cell-two gonadotropin)

Hypothalamus secretes GnRH.

GnRH travels to anterior pituitary to stimulate gonadotropins: FSH and LH

Females are born with all of the stem cells, called ‘oogonium’, a female ever
needs
- oogonium converts into primordial follicle
- happens pre-puberty, childhood
- when the female reaches puberty, localized androgens stimulate conversion
of primordial follicle into primary follicle
primary follicle
 contains primary oocyte
o hasn’t undergone meiosis I and still frozen at prophase I
o a single layer cuboidal columnar like follicle cells

- Primary follicle is converted into Early Secondary Follicle with the help of FSH
- Cuboidal cells proliferate to form multiple layers of granulosa cell
- FSH stimulates the oocyte to produce glycoprotein membrane around it
called Zona pellucida
- Production of estrogen
 Key player: thecal cell
 Thecal cells are right next to granulosa cells
a. LH stimulates conversion of cholesterol to androgens in thecal cells
b. Right next to androgens in thecal cells, are granulosa cells
c. Androgen moves into granulosa cells
d. FSH stimulates conversion of androgen into estrogen

- Early secondary follicle  Late secondary follicle  Graafian follicle

- Proliferate
- Granulosa cells begin to produce pockets of follicular fluid
- Produce estrogen
  8~9 days into follicular phase, estrogen level in blood spike
 Rise in estrogen level exerts a negative feedback mechanism
i. Rise in estrogen level
ii. Estrogen inhibits hypothalamus to secrete GnRH
1) in result, inhibits anterior pituitary from releasing FSH and LH
iii. not as much FSH and LH produced
1) in result, estrogen level drops
 13~14 days in, estrogen level start rising in the blood again and exert a
positive feedback mechanism
“LH surge”
o Induces cumulus expansion by secreting hyaluronic acid
o Induces oocyte maturation
 Oocytes progress from Prophase I to Metaphase
II
o Stimulates hypothalamus to produce tons of GnRH
o Stimulates anterior pituitary to secrete LH, not as much FSH
Why?
 At the end of the follicular phase, Graafian follicle notices the
rise in estrogen
o as a result of high estrogen level in blood, produces
inhibin
o Inhibin inhibits anterior pituitary from releasing FSH
- Result of LH surge
 LH travels to graafian follicle
 LH stimulates increase in blood flow and permeability to
the graafian follicle to produce more follicular fluid
 Activates special enzymes
 Proteases
: eats away the tissue around the graafian follicle and cuts
out the secondary oocyte that was frozen at metaphase II
o ovulation (beginning of ovulatory phase: day 14~15)
Luteal Phase
- LH triggers conversion of the graafian follicle that was ruptured to corpus
luteum
- LH directly stimulates corpus luteum and produce progesterone

In summary,
i. Follicular phase
- Day 0~14
- Primordial  graafian
- Mainly FSH, little bit of LH
- Mitosis
- Estrogen produced
- Follicular fluid
- Primary oocyte  secondary oocyte

ii. Ovulatory phase

- Day 14~15
- LH surge

iii. Luteal Phase

- Graafian  corpus luteum
- LH produces progesterone

2. Describe the hypothalamic and pituitary regulation of steroid hormone

production in the female

Production of a releasing hormone GnRH by the hypothalamus stimulates the

pituitary's anterior lobe to release FSH and LH.
• FSH and LH stimulate egg maturation and estrogen production.
 Occurs in the ovary
• Estrogen production leads to rise in estrogen level in blood.
• High estrogen levels trigger a surge in LH which brings about the release of
an egg and formation of the corpus luteum.
• This glandular structure releases progesterone and estrogen.
• During the last phase of the cycle, the rising blood levels of progesterone and
estrogen feedback to the hypothalamus and the pituitary to inhibit secretion of
LH and FSH.
3. Compare the timing of negative and positive feedback by estrogen
during the menstrual cycle

Menstrual cycle can be divided into 2 phases

- Follicular phase (day 0-14)
- Primordial  graafian
- Primary oocyte  secondary oocyte
- Luteal phase (day 14-28)

Follicular phase
At the beginning of menstrual cycle, there is a increase in gonadotropin releasing
hormones (GnRH) by the hypothalamus
- This should increase steady increase in FSH and LH
- But instead, there is an increase and then a slow dropping level of FSH
- And steady level of LH
Why?
 In the first ten days, steady low concentration of LH due to
inhibitory effects of estrogen.
 Steady drop of FSH due to increase in estrogen levels

- FSH initially rises

- because during follicular phase, FSH will enter the ovaries and
stimulate follicle maturation of the primary follicles
 some primary follicles mature into secondary follicle
 during maturation of follicles, hormone called Estrogen is
produced
*Estrogen has many effects
- in the first 10 days of cycle, estrogen has negative feedback on pituitary
gland
o inhibits the release of LH
o at low concentration, estrogen inhibits LH secretion from anterior
pituitary
 reason why there is a steady level of LH in the blood
 even though GnRH stimulates the release of LH, at low
concentrations estrogen will inhibit LH release
 - FSH is secreted primarily in response to low estrogen
o When estrogen level rise, FSH will fall
 Reason why there is a steady drop in FSH (increase in
estrogen levels)

As follicles mature, they will produce more estrogens

- At low concentration, estrogen inhibits secretion of LH
- Increase in estrogen concentration causes decrease in FSH secretion

Day 10~13/14
After 10 days, estrogen level continues to rise as follicles mature in the ovaries
- Has positive feedback
- Stimulates the release of LH
o High concentration of estrogen stimulates LH secretion

Day 13/14
Increase in GnRH and estrogen stimulates LH secretion
- Thus the massive spike in LH concentration that triggers ovulation of the
most mature follicle in the ovary
- Ovulation of the follicle releases the oocyte (egg)
- LH triggers ovulation and oocyte is released

Luteal phase: formation of corpus luteum

After ovulation, LH level drops back down
- GnRH drops
- FSH has small spike due to side effect of increase of LH secretion

After follicle ovulates, follicle turns into corpus luteum

- corpus luteum is a dead follicle
- corpus luteum will sow degrade
purpose of corpus luteum
o secretes three hormones
 estrogen
 inhibin
 progesterone
 What do these hormones do?
Inhibin
- Has a negative feedback
- Inhibits the secretion of FSH because at luteal phase, we don’t need more
follicles to mature just yet

Progesterone
- Negative effect on hypothalamus
- Stimulates endometrial growth
o Endometrial lining is the lining of the uterus which shed each month
o Where egg implants if fertilized
- Inhibits the secretion of GnRH
o Effects release of LH and FSH
o After ovulation during the luteal phase, Progesterone levels increase
slowly and estrogen levels decrease slowly
 This suppresses GnRH

Increase in progesterone and inhibin during the luteal phase, causes a decrease
in GnRH, LH and FSH

Corpus luteum degenerates and allows a new set of follicles to mature

- All hormones produced by Corpus luteum decrease
 when corpus luteum degenerate, progesterone decrease  GnRH level
increase since progesterone cannot inhibit GnRH release  allows new
menstrual cycle to occur

- Since decrease in progesterone and estrogen, hormones cannot maintain

the endometrial lining of uterus and shed (period)

4. Fraternal twins vs identical twins

- fraternal twins arise from separate ova fertilized by separate sperm, they
share no more in common than any other two siblings except for the same
birth date.
 - Identical twins develop from a single fertilized ovum that completely divides
into two separate, genetically identical embryos at a very early stage in
development.

4. Describe ovarian follicular development and its hormonal regulation

Characteristics of follicle growth
1) proliferation of granulosa cells (primary follicle)
2) Zona pellucida deposition by oocyte
3) stromal cells differentiate into theca cells
4) Antrum formation (Graafian follicle)
5) differentiation of granulosa cells
- cumulus granulosa cells - get ovulated with oocyte
- mural granulosa cells - become corpus luteum
6) Oocyte grows in diameter

Primary oocyte = primordial germ cell surrounded by layer of granulosa

5. Compare and contrast the processes of spermatogenesis and oogenesis

Oogenesis process
: process of producing eggs

Steps of oogenesis
Inside the ovaries of a female animal are diploid germ cells called oogonia.
- An oogonium grows to become a primary oocyte (diploid).
- Meiosis 1 followed by unequal cytoplasmic division produces one large
secondary oocyte in a smaller polar body, both are haploid.
- Completion of meiosis and a second round of unequal cytoplasmic division
produce one large secondary oocyte and 3 smaller polar bodies.
- The secondary oocyte will function as a gamete
- also called an ovum or egg.
- The polar bodies will degenerate.

Oogenesis
- Starting from a primary oocyte, the first phase of meiosis produces a single
secondary oocyte and the first polar body, a small residual cell with very little
cytoplasm
- Second phase of meiosis create one mature oocyte and three polar bodies

- Timing of meiosis producing mature oocyte is very complex

- Early in development, XX germ cells begins first phase of meiosis but
arrest in prophase forming oocytes surrounded by follicular cells
 Doesn’t complete the first step of meiosis until later
- Follicular cells and oocytes together create primordial follicle
 Follicular cells grow to become cuboidal in primary follicle
- As primary follicles mature, follicular cells proliferate and secretes layer of
glycoprotein around oocyte called zona pellucida
- Important to protecting the egg as it migrates down the oviduct and may
or may not be fertilized
- During each menstrual cycle, several primary oocytes grow larger and
follicular cells surrounding them proliferate to become granulosa cells
- Once granulosa cells proliferate to the point where they can no longer
sustain themselves, they begin to form small vacuoles called lacunae
within the secondary follicle
- As secondary follicle mature, lacunae fuse to form follicular antrum,
- Prior to ovulation, follicular antrum enlarges and creates mature Graafian
follicle
Graafian follicle
: entire assemblage of follicular cells, oocyte and connective tissue
 Subdivisions of connective tissue surrounding the follicular cells
Theca externa
- Anchors it to the egg

Theca interna
- Secretes hormones that affect oocyte’s development and make it
capable of fertilizing if ovulated

Follicular cells: thecal + granulosa cells

During each menstrual cycle, several follicles race each other to develop
Graafian follicle stage but typically only one is released from the egg to the
oviduct
- Follicular antrum ruptures and egg moves out into the reproductive tract

Comparison between spermatogenesis and oogenesis

- Identical step of chromosome replication and division
- Except, cytoplasmic distribution and time span for completion
- Just as 4 haploid spermatids are produced by each primary spermatocyte, 4
haploid daughter cells produced by each oocyte (if the first polar body does
not degenerate before it completes second meiotic division)

- Primordial germ cells enter the ovaries/testis early in development and

develop oogonia
- they divide mitotically to create primary oocyte
- Enters meiosis (where female and male differentiates)

Difference between spermatogenesis and oogenesis

I. Location
a. Spermatogenesis  testes
b. Oogenesis  ovaries
II. Stem cells
a. Spermatogenesis  spermatogonia
b. Oogenesis  oogonia
III. Number of cells produced
 a. Spermatogenesis produces four sperm cells from each primary
spermatocyte
b. Oogenesis produces one egg and three polar bodies from each
primary oocyte
IV. Fates of daughter cells
a.  Spermatogenesis:
i. each primary spermatocyte gives rise to 4 spermatids that all
become spermatozoa
b. Oogenesis,
i. Only primary oocyte remains at birth
ii. Each primary oocyte gives rise to one ovum
iii. Other daughter cells (polar body) degenerates
V. Timing of meiosis
a. Spermatogenesis:
i. Begins at puberty and continues until death
b. Oogenesis
i. Arrested at prophase of meiosis I
ii. Resumed at ovulation (puberty)
iii. Second meiotic division after fertilization
iv. Process ceases after menopause
VI. Cytoplasmic division
a. spermatogenesis
i. Cytoplasm is divided equally between daughter cells
ii. Almost all cytoplasm shed during spermiogenesis
b. Oogenesis
i. Oocyte receives most of cytoplasm
ii. Polar bodies get chromosomes but almost no cytoplasm
VII. Time it takes to develop
a. Spermatogonium to spermatozoa takes two months to develop
b. Oogonium (present before birth) to mature ovum takes 11~50 years
(beginning of ovulation at puberty to end of ovulation at menopause)

6. Describe ovulation and its regulation

Ovulation
: release of mature eggs from ovaries in females
- Process of graafian follicle in the ovary ruptures and ovary is released into the
abdominal cavity
- Process occurs on the 14 day of the menstruation cycle in a normal cycle of
28 days
- occurs in response to the LH surge (about 36 hours later)
- most common cause of twins is ovulation of two follicles
- oocyte and cumulus cells ovulate
- move into oviduct aided by fimbriae
- move through oviduct aided by cilia

Hormonal regulation of ovulation

- In the follicular phase during first days of menstrual cycle, the hypothalamus
secretes GnRH
- GnRH stimulates the anterior pituitary to secrete two gonadotropins
 FSH and LH
- Gonadotropins activate the ovaries
- Development of primordial follicles
- Only one follicle in one of the two ovaries produces egg cells
 Remainder degenerates
- FSH stimulates the follicular cells to proliferate
- Follicle first develops multilayer wall
 Known as granulosa cells
- Then develops a cavity called antrum
- Developing follicle begins to secrete estrogen
- As estrogen level in blood increases, it inhibits the secretion of FSH by
negative feedback system
- Rapid increase in estrogen in the 11th day of the cycle stimulates the
hypothalamus again
 Leads to intensive secretion of FSH and LH via positive feedback
- High level of LH and FSH causes the follicle (Graafian follicle) to burst
- Releasing the secondary oocyte

7. Describe the corpus luteum as a transient endocrine structure

 CL
- structure in the ovary that develops after ovulation
- follicular basement membrane breaks down
- granulosa and theca cells differentiate into luteal cells
- CL secretes progesterone and oestrogen
- pregnancy: CL persists 3-4 months
- no pregnancy: CL spontaneously degenerates after 2 weeks becomes
corpus albicans that is eventually degraded

Transient endocrine structure

: temporary endocrine gland presents only during certain stages of development

At ovulation, old follicular cells transform to form corpus luteum via a process
called luteinization

Formation of Corpus luteum

- Becomes highly vascularized as blood vessels from the thecal region invade
the granulosa
- These changes are appropriate for its functions

 To secrete into the blood abundant quantities of progesterone along

with smaller amounts of estrogen
o Estrogen secretion in the follicular phase followed by
progesterone secretion in the luteal phase is essential for
preparing uterus for fertilization
- Fully functional within 4 days of ovulation

Degeneration of corpus luteum

- If the released ovum is not fertilized and does not implant, corpus luteum
degenerates within 14 days of its formation
- Luteal cells degenerate and is phagocytized
- Luteal phase is now over, and one ovarian cycle is complete
- New wave of follicular development begins when the degeneration of
old corpus luteum has completed
Corpus Luteum of Pregnancy
- If fertilization and implantation do occur, the corpus luteum continues to grow
and produce increasing amount of progesterone and estrogen
- Ovarian structure persists until pregnancy ends
- Provides hormones essential for maintaining pregnancy until the developing
placenta can take over this crucial function

8. Describe the cyclical regulation of the uterine endometrium

-  Early in the follicular stage, FSH and LH stimulate growth of an ovarian

follicle.
- During the same period, the endometrial lining is sloughed off.
- As the follicle grows, it secretes estrogen, estrogen levels rise, causing
thickening of the endometrium.
- When the level of estrogen peaks, it triggers a surge in LH.
- The LH surge brings about ovulation of the now mature follicle.
- The old follicle cells are transformed into the corpus luteum.
- The corpus luteum secretes both estrogen and progesterone.
- The progesterone primes the uterine wall for implantation.
- If fertilization and implantation do not occur, the corpus luteum
degenerates, progesterone and estrogen levels drop, and menstruation
and a new follicular phase begin.

Uterine Cycle:
- humans: menstrual cycle  monthly shedding of uterine tissue
- other mammals: estrous cycle  no shedding, behavioural changes

Three phases:
1) Menstrual
- initiated by decrease in progesterone and estradiol levels (CL
degeneration)
o Because the net effect of progesterone and estrogen is to prepare
the endometrium for implantation of a fertilized ovum, uterine lining
deprives of its hormonal support
 - lasts 3-5 days (variable)
- total blood loss is ~50 ml (variable)
2) Proliferative
- simultaneous with last portion of follicular stage of ovarian cycle
- ovarian estradiol
- stimulates proliferation of endometrium
- thickens the lining to 3~5mm
- increases number of spiral arteries and glands
- ends at time of ovulation
3) Secretory
- simultaneous with luteal stage of ovarian cycle
- ovarian estradiol and progesterone
- increases gland secretion of glycoproteins
- increases thickness to 4-6 mm
- provides environment for embryo implantation
- ends when CL degenerates  progesterone and estradiol decrease
- prostaglandin levels increase  constriction of spiral arteries, tissue dies
- prostaglandin also causes contractions of uterine muscle (cramping

9. List the effects of the estrogen and progesterone in the body

Influence on uterine
Uterus consists of two layers
- myometrium
- outer smooth muscle layer
- endometrium
- inner lining that contains blood vessels and glands

Estrogen stimulates growth of both myometrium and endometrium

- induces synthesis of progesterone receptors in endometrium
- endometrium must be primed by endometrium before progesterone can
exert effect on it
Progesterone acts on estrogen primed endometrium to convert it into lining
suitable for implantation of fertilized ovum

Effects of Oestrogen:
1) ovary
- stimulates granulosa cell proliferation and ovulation (positive feedback)

2) uterus
- endometrium  proliferation (thickening)
- myometrium  increases amount of muscle - actin and myosin production

3) vagina
- proliferation of epithelium
- thins cervical mucus

4) mammary glands
- lengthening of glands
- increases adipose tissue

5) secondary sex characteristics

- normal function and structure of accessory sex organs
- subcutaneous fat deposits
- broadens pelvis
- breast development
- shortens period of long bone growth

6) prevents bone loss

Effects of Progesterone:
1) uterus
- endometrium
- proliferation
- coiling of glands and vasculature
- maintenance of endometrium during pregnancy
- myometrium
- decreases excitability
 - decreases responsiveness to oxytocin

2) cervix
o thickens mucus

3) mammary glands
o branching of duct system (arborization)
o progesterone + prolactin - increase alveolar development at end of ducts
o inhibits milk production

4) increases body temperature - 0.5 to 0.75 oC in luteal phase

Effects of LH:
- 2 modes of secretion: tonic secretion, LH surge
- triggers resumption of meiosis by the oocyte
- induces follicular rupture (ovulation)
- luteinization: transition from follicle into corpus luteum
- stimulates progesterone production by corpus luteum
- stimulates testosterone production by theca cells
 
Effects of FSH
- stimulates follicle development, granulosa cell proliferation
- stimulates estradiol production by granulosa cells
6. Describe the process of fertilization

Process of fertilization
- occurs in ampulla, upper third of the oviduct (fallopian tube)
- both sperm and ovum must be transported to ampulla

Ovum transport to the oviduct

- At ovulation, ovum is released and picked up by the oviduct
- Fimbriae, finer like projections that contract in a sweeping motion
guides the released ovum into the oviduct
- Cilia, hairlike projections that beat in waves toward interior of the
oviduct assures the ovum’s passage into oviduct

- Conception takes place during fertile period

- If not fertilized,
- Ovum begins to disintegrate within 12~24 hours
 Subsequently phagocytized
- Fertilization must occur within 24 hours after ovulation
- When ovum is still viable
- Sperm survive 48 hours~5days in the female reproductive tract, so
sperm deposited five days before ovulation to 24 hours after
ovulation may fertilize the released ovum

Sperm Transport to the oviduct

- Once sperm is deposited, it travels through the cervical canal, the uterus, and
then to the egg in the ampulla (upper third of the oviduct)
- First sperm arrive in the oviduct within half an hour after ejaculation
- Even though sperm is mobile, 30 minutes is too soon
- Female reproductive tract helps (following)

 First hurdle is passage through cervical canal

o Cervical mucus is usually too thick to permit sperm penetration
due to high progesterone or low estrogen levels
 o Cervical canal becomes thin and watery enough for
transportation of sperm when estrogen level is high, as in
presence of mature follicle about to ovulate
o Sperm migrate up the cervical canal by themselves
 Canal is only penetrable 2~3 days around ovulation

 Once sperm enters the uterus

o Contraction of myometrium churns them around in “washing
machine” fashion
o Sperm is dispersed throughout the uterine cavity
o When sperm reaches oviduct, they are propelled to ampulla by
upper contraction of oviduct smooth muscle cells

- Once sperm reaches ampulla, ova are not partners in conception

 Mature eggs release alluring
 Chemical that attracts sperms
 Causes them to propel themselves towards waiting
gamete

Fertilization
I. Capacitation
- Sperm penetrates corona radiata via membrane bound enzymes
- Sperm penetrate zona pellucida by binding with specific sites on the
surface (ZP3: Zona Pellucida 3)

II. Acrosomal Reaction

Penetration through zona pellucida
Fertillin
- Protein found on PM of the sperm
 Binding partners between sperm and ovum
 Binds to ZP3
- Binding of sperms induces inflow of Ca2+and triggers acrosome reaction
- Acrosomal membrane opens up and vesicle of the acrosome fuses
to release acrosomal enzymes
 - Acrosomal enzymes digest the zona pellucida, enabling the sperm
to tunnel through the protective barrier
First sperm to penetrate the zona pellucida fuses with PM of ovum
(secondary oocyte)
- Head of sperm, bearing DNA enters ovum’s cytoplasm
- Sperm’s tail is lost but the head carries the genetic info

III. Fast block to polyspermy

Reaction of Beta part of protein on sperm with oocyte membrane opens up
specific channels
- Sodium ions starts flowing into the cell
 Sodium ions create positive charge across the membrane
As a result, any other sperm that wasn’t first is blocked from
binding to the oocyte membrane
• Phenomenon known as block to polyspermy

 Once other sperms are blocked, alpha subunit of sperm cell

binds with the oocyte membrane and fuse
 can now release its nuclear material into the oocyte
cytoplasm

IV. Slow block to polyspermy

(a)Once the sperm cell moves in, smooth ER is activated and stimulates
production of calcium
- Calcium activates lysosomes
- Lysosomes migrate to cortical parts of the egg cell
 Lysosome fuses with cell membrane
 Lysosomes degrades zona pellucida and harden the cell
membrane
 Other sperm cells don’t have anything to attach to
(absence of zona pellucida)

(b)Exocytosis of enzyme filled cortical granules diffuse into zona pellucida

to inactivate receptors associated with Fertillin to inhibit any further binding
of sperm to zona pellucida
 - Enzyme hardens zona pellucida and seal off the tunnel

Completion of Meiosis II
- Calcium activates secondary oocyte that’s frozen in metaphase II to
finish meiosis II
 New fertilized (definitive) ovum and polar body produced after
meiosis II
 Secondary oocyte  mature ovum

V. Production of zygote
When male pronucleus (n) and female pronucleus (n) fuse, zygote (2n) is
formed
- Beginning point of embryo
- Conception has occurred

In summary
- ovulation release a secondary oocyte and first polar body enclosed within a
non-cellular zona pellucida and remnants of the follicle.
- If sperm meet up with such an oocyte, they surround it and release digestive
enzymes that clear a path through the zona pellucida.
- Although many sperm get this far, usually only one penetrates the secondary
oocyte.
- Inside the oocyte cytoplasm, the sperm degenerates until only its nucleus and
the centrioles remain.
- Penetration induces the secondary oocyte to finish meiosis. There are now
three polar bodies and a mature ovum or egg.
- The sperm nucleus and egg nucleus fuse.
- At fusion, fertilization is over. The diploid zygote has formed, and the
development will begin.

1. summarize the main features of early embryonic development up to

implantation

I. Ovulation
- hypothalamus releases GnRH
- GnRH stimulates anterior pituitary to secrete large amounts of LH
- Positive feedback cycle of Estrogen also triggers secretion of LH
 Positive feedback cycle when estrogen increase again during
the second time

LH is released and transports to ovary via blood

- LH stimulates ovary to produce lots of fluid to pressurize the graafian follicle
which contains secondary oocyte
- Increase leakiness of capillaries of graafian follicle
 Activates enzymes to break down connective tissue around
follicle
 Helps to pop out the secondary oocyte

Once oocyte is out, fimbriae begin to transport oocyte towards ampulla

- At this stage, oocyte is secondary oocyte
- Underwent meiosis I, getting ready to finish meiosis II
 Once it ovulates, secondary oocyte is stuck metaphase II
 Waiting for sperm to touch
 Once sperm touches, secondary oocyte completes
meiosis II
o Prepares for fusion

Once sperm is ejaculated, sperm travels up the vagina, through the cervix
of the uterus and fallopian tubes, to meet with secondary oocyte at
metaphase II at ampulla

II. Fertilization
In order for sperm to touch the egg, sperm must undergo capacitation and attach
to ZP3
- Once sperm cell touches ZP3, sperm cell is activated
- Head of the sperm cell fuse with the oocyte membrane
 Releases its nucleus into the cytoplasm

23 chromosomes in sperm cell nucleus and 23 chromosomes in oocyte cll

nucleus
- 23 are paternal and 23 maternal fuse to produce 46 chromosomes
- Zygote (46 chromosomes) produced

III. Cleavage
Zygote proliferates and replicates (cleavage)
- Zygote goes into two-cell-stage
- Zygote divides again to produce four cells (four-cell-stage)
 Zygote divides again (eight-cell-stage)
 Zygote divides again (16 cell stage)

Interesting structure formed after 16 cell stage (marula)

- Divided zygote cell surrounds the entire structure
- Inside the centre of the cell is hollow (nothing in there)
- All of the cells are forming the outer coat
q This structure is known as marula
- Anything from 16 cells and up until blastocyst

q Once cell is at the level of marula, they are called blastomeres

IV. Blastulation
- Process from marula to blastocytes is blastulation
- Forms blastocyst
- Marula takes the cells forming the edge and compacts it towards one edge to
convert to blastocyst
- Conversion of hollow ball to cell lining around the edge and group of
cells clumped together in one edge

Within blastocyst, fluid cavity is present

- Clumped up group of cells  inner cell mass
- Cells around the lining/edge  outer cell mass

Inner cell mass and outer cell mass continue to differentiate and develop,
- Outer cell mass becomes trophoblast
- Trophoblast differentiates into cytotrophoblast and
syncytiotrophoblast
- Inner cell mass becomes embryoblast
 - Embryoblast differentiates into bilaminar disc
 Epiblast and hypoblast

2. Define sperm capacitation and indicate its relevance to fertility

As sperm migrate towards zona pellucida, capacitation

- Cleans the head of sperm by removing cholesterol and modifying
glycoproteins
- Increases motility of the sperm
- As result, only specifically modified glycoproteins leftover

3. Describe the acrosome reaction

Acrosomal Reaction
Penetration through zona pellucida
Fertillin
- Protein found on PM of the sperm
 Binding partners between sperm and ovum
 Binds to ZP3
- Binding of sperms induces inflow of Ca2+and triggers acrosome reaction
- Acrosomal membrane opens up and vesicle of the acrosome fuses to
release acrosomal enzymes
- Acrosomal enzymes digest the zona pellucida, enabling the sperm to
tunnel through the protective barrier
First sperm to penetrate the zona pellucida fuses with PM of ovum (secondary
oocyte)
- Head of sperm, bearing DNA enters ovum’s cytoplasm
- Sperm’s tail is lost but the head carries the genetic info

- Ensures same-species fertilization

3. Define polyspermy and describe the mechanisms that block to

polyspermy
Fast block to polyspermy
Reaction of Beta subunit on sperm with oocyte membrane opens up specific
channels
- Sodium ions starts flowing into the cell
 Sodium ions create positive charge across the membrane
As a result, any other sperm that wasn’t first is blocked from binding
to the oocyte membrane
• Phenomenon known as block to polyspermy

 Once other sperms are blocked, alpha subunit of sperm cell binds
with the oocyte membrane and fuse
 can now release its nuclear material into the oocyte cytoplasm

Slow block to polyspermy

(a)Once the sperm cell moves in, smooth ER is activated and stimulates
production of calcium
- Calcium activates hydrolytic enzymes/lysosomes
- hydrolytic enzymes/lysosomes migrate to cortical parts of the egg cell
 hydrolytic enzymes/lysosomes fuses with cell membrane
 hydrolytic enzymes/lysosomes degrade zona pellucida and harden
the cell membrane
 Other sperm cells don’t have anything to attach to (absence of
zona pellucida)
- Calcium stimulates contraction and release of cortical granules
 Calcium exocytosis cortical granules out via cortical reaction
 Causes conversion of zona pellucida into solid
impenetrable membrane
o No more sperms

5. Define zygote; summarize the developmental steps that occur while the
embryo is traversing the oviduct

Zygote
: fertilized ovum (followed by union of male and female chromosomes)
During the first 3~4 days following fertilization, zygote remains within the ampulla

The beginning steps

Zygote divides mitotically to form morula
- Morula: rapid mitotic cell division of zygote to form a solid ball of cells

Rising level of progesterone from newly developing corpus luteum that formed
after ovulation stimulate the release of glycogen to use for energy by early
embryo

Descent of the morula to the uterus

2~3 days after ovulation, progesterone is produced to relax oviduct constriction
- Permits morula to rapidly propel into the uterus by oviductal contraction and
ciliary activity
- When morula descends to uterus, morula floats within the uterine cavity for
3~4 days
- Uterine cavity prepares for implantation under the influence of Luteal phase –
progesterone
- Uterus is in secretory phase (pregestational phase) storing glycogen
and becomes richly vascularized

Implantation of the Blastocyst in the prepared endometrium

Endometrium is suitable for implantation at about a week after ovulation
- Morula has descended to the uterus and continued to differentiate into
blastocyst capable for implantation
- Blastocyst: single later hollow ball of about 50 cells encircling a fluid
filled cavity, with a dense mass of cells grouped on one side

 Dense mass = inner cell mass  becomes embryo/fetus

 Thin outermost layer = trophoblast, accomplishes implantation

- Before blastocyst implant, zona pellucida must shed and undergo a process
called zona hatching
- process by which a blastocyst emerges from its protective outer
layer, the zona pellucida, and attaches to the lining of the uterus, a
process called implantation.
 - Blastocyst adheres to the uterine lining on the side of its inner cell
mass
 necessary for the blastocyst to establish a proper connection
with the uterus and to obtain nourishment from the mother

- Implantation begins when, on contact with endometrium, the trophoblastic

cells overlying the inner cell mass release protein digesting enzymes
- These enzymes digest pathways between endometrial cells and
permits penetration into the depths of the endometrium
 Continues to digest uterine cells

Through its cannibalistic actions, trophoblast performs dual function

a) accomplishing implantation as it carves out a hole in endometrium for
blastocyst
b) makes metabolic fuel and raw materials available for the developing
embryo while the advancing trophoblastic projections break down nutrient
rich endometrial tissue

6. Cleavage and implantation

Fertilization typically takes place in the upper part of the oviduct.

- Cleavage begins as the zygote moves to the oviduct toward the uterus.
- Continued mitotic divisions produce a ball of 16 to 32 cells called a morula.
o By the fifth day, a blastula has formed with a surface layer of cells
surrounding a fluid-filled blastocoel and an inner cell mass.
o About a week after fertilization, implantation is under way.
- The blastocyst adheres to the endometrium that lines the uterus and
begins to send out projections into the maternal tissues.
- As implantation proceeds, the inner cell mass develops into an embryonic
disk that is two cell layers thick.
o This will give rise to the embryo.
- Membranes start to form around the embryonic disk.
- Spaces in the maternal tissue around the implanting blastocyst open and
fill with blood.
 o Inside the blastocyst, a chorionic cavity opens around the amnion
and the yolk sac.
o The membrane that lines this cavity is the chorion, it will become
part of the placenta.

7. Define morula, blastocyst, hatching

Morula

Blastocyst
- Single layer hollow ball of about 50 cells resulting from mitotic division of
zygote
- Developmental stage that implants in endometrium

Hatching

7. Identify the three essential steps in reproduction that are targeted by

contraceptives
i. Blockage of sperm transport of the ovum
ii. Preventing ovulation
iii. Blockage of implantation

7. Compare the failure rates of barrier vs. hormonal contraception

Barrier methods = 10-15 / 100 average failures

Hormonal contraception = 20 / 100 average failures

7. Summarize the hormonal regulation of pregnancy, parturition and

lactation

1. Identify the origins of the components of the placenta

The placenta is an organ that develops in the uterus during pregnancy. It is
responsible for providing oxygen and nutrients to the developing fetus, and
removing waste products. The placenta is composed of two main parts: the fetal
portion and the maternal portion.

The fetal portion, also known as the chorionic villi, develops from the fertilized
egg and is composed of trophoblastic cells. These cells also give rise to the
chorionic membrane, which surrounds the fetus.

The maternal portion, also known as the decidua, is derived from the lining of the
uterus. The decidua is composed of decidual cells, which are modified
endometrial cells. The decidua also gives rise to the maternal blood vessels that
run through the placenta and provide oxygen and nutrients to the fetus.

Together, the fetal and maternal portions of the placenta form the barrier that
separates the maternal and fetal blood supplies, allowing for the exchange of
oxygen, nutrients, and waste products

- By day 12, the embryo is completely embedded in the decidua.

o By this time the trophoblastic layer is two cell layers thick and is
called the chorion.
o Decidua: endometrial tissue at the implantation site to support
implanting embryo
- As the chorion continues to release enzymes and expand, it forms an
extensive network of cavities within the decidua.
o As the expanding chorion erodes decidual capillary walls,
maternal blood leaks from the capillaries and fills these
cavities.
 The blood is kept from clotting by an anticoagulant
produced by the chorion. Finger-like projections of
chorionic tissue extend into the pools of maternal blood.
- Soon the developing embryo sends out capillaries into these
chorionic projections to form placental villi.
- Some villi extend completely across the blood-filled spaces to anchor
the fetal portion of the placenta to the endometrial tissue, but most
simply project into the pool of maternal blood.
- Each placental villus contains embryonic (later fetal) capillaries
surrounded by a thin layer of chorionic tissue, which separates the
embryonic/fetal blood from the maternal blood in the intervillus
spaces.
- Maternal and fetal blood do not actually mingle, but the barrier
between them is extremely thin.
 o only the thin chorionic tissue (plus the capillary wall of the fetal
vessels) separates the fetal and maternal blood.
o All exchanges between these two bloodstreams take place
across this extremely thin barrier.
o This entire system of interlocking maternal (decidual) and fetal
(chorionic) structures makes up the placenta.

2. describe the fetal-placental circulation

By 5 weeks after implantation, placenta is established and operational

- The heart of developing embryo is pumping blood into the placental villi
and embryonic tissues
o Through gestation, fetal blood traverses between placental villi and
circulatory system via umbilical cord
 Life line between fetus and placenta

The fetal-placental circulation refers to the blood flow between the fetus and
the placenta. It is a unique circulatory system that is separate from the
maternal circulation.

The blood flow begins in the fetal heart, where it is pumped into the umbilical
artery. The umbilical artery carries oxygen-poor blood from the fetus to the
placenta. Once the blood reaches the placenta, it flows through the chorionic
villi, which are the finger-like projections on the fetal side of the placenta. The
oxygen and nutrients from the mother's blood are exchanged across the
chorionic villi into the fetal blood, and waste products such as carbon dioxide
are transferred into the maternal blood.

The oxygen-rich blood then flows back to the fetus through the umbilical vein.
The umbilical vein carries the oxygen-rich blood from the placenta to the
fetus, where it enters the fetal heart and is pumped to the rest of the body.

It's worth mentioning that the umbilical cord contains two umbilical arteries
and one umbilical vein. The umbilical vein carries oxygen-rich blood and
nutrients to the fetus, while the two umbilical arteries carry deoxygenated
blood and waste products away from the fetus to the placenta.

3. List the functions of the placenta

 - exchange of gases (O2, CO2) by diffusion between fetus and mother
- delivery of nutrients by diffusion and active transport from mother to fetus
- delivery of antibodies from mother to fetus
- removal of fetal waste products
- secretion of hormones: hCG, progesterone, estradiol, hPL

4. Describe the differences between fetal and adult hemoglobin

HbF
- composed of 2 alpha subunits and 2 gamma subunits
o results in higher affinity for oxygen than HbA
 binds to oxygen more tightly and release it less easy
 allows for more oxygen extraction from mother’s blood
- produced primarily during fetal development
- production starts to decline after birth and replaced by HbA
- shorter lifespan

HbA
- composed of two alpha subunits and two beta subunits
o less affinity for oxygen than HbF
- produced primarily after birth
- replaces HbF after birth

5. List the three stages of parturition (labour, delivery, birth)

i. labour
ii. delivery
iii. birth
Parturition requires
- dilation of the cervical canal to accommodate passage of the fetus from the
uterus through the vagina and to the outside
- contractions of the uterine myometrium that are sufficiently strong to expel
the fetus
 role of oxytocin during parturition and ruing breast feeding
- Oxytocin promotes uterine muscle contractions that force the fetus against
the cervix, dilating it and triggering a neuroendocrine reflex that results in
secretion of even more oxytocin, which stimulates even stronger
contractions, and so on as labour progresses until the cervix is dilated
sufficiently for the baby to be pushed out.
- During breastfeeding, oxytocin causes milk ejection (milk letdown) by
stimulating contraction of the myoepithelial cells surrounding the milk-
secreting alveoli.

6. Describe the process of labour

At the beginning of labour

: contractions lasting 30 seconds or less occur about every 25 to 30 minutes

By the end
: contraction last 60 to 90 seconds and occur every 2 to 3 minutes.

Each uterine contraction begins at the top of the uterus and sweeps downward,
forcing the fetus toward the cervix.
- Pressure of the fetus against the cervix does two things.
1. the fetal head pushing against the softened cervix wedges open the
cervical canal.
2. cervical stretch stimulates the release of oxytocin through a
neuroendocrine reflex.

Stimulation of receptors in the cervix in response to fetal pressure sends a neural

signal up the spinal cord to the hypothalamus
- triggers oxytocin release from the posterior pituitary.
- This additional oxytocin promotes more powerful uterine contractions.
o As a result, the fetus is pushed more forcefully against the cervix,
stimulating the release of even more oxytocin, and so on.
This cycle is reinforced as oxytocin stimulates prostaglandin production by the
decidua. Prostaglandin further enhances uterine contractions.
Oxytocin secretion, prostaglandin production, and uterine contractions continue
to increase in positive-feedback fashion throughout labour until delivery relieves
the pressure on the cervix.

Stages of labour
- Cervical dilation
- Delivery of the baby
- Delivery of placenta

7. Summarize the neuroendocrine regulation of the onset and completion

of parturition

Role of high estrogen level

During early gestation, maternal estrogen levels are relatively low, but as
gestation proceeds, placental estrogen secretion continues to rise.
In the immediate days before the onset of parturition, soaring levels of estrogen
bring about changes in the uterus and cervix to prepare them for labour and
delivery
iv. high levels of estrogen promote the synthesis of connexons within the
uterine smooth muscle cells.
v. newly manufactured connexons are inserted in the myometrial plasma
membranes to form gap junctions that electrically link together the uterine
smooth muscle cells so they become able to contract as a coordinated
unit.
1. Simultaneously, high level of estrogen increases the concentration
of myometrial receptors for oxytocin
i. Brings about increased uterine responsiveness to oxytocin
which initiates labour

vi. increasing levels of estrogen promote production of local

prostaglandins
1. contribute to cervical ripening by stimulating cervical
enzymes that locally degrade collagen fibres.
 i. these prostaglandins themselves increase uterine
responsiveness to oxytocin.

Role of oxytocin

Oxytocin is a peptide hormone produced by the hypothalamus, stored in

the posterior pituitary, and released into the blood from the posterior
pituitary on nervous stimulation by the hypothalamus.

vii. A powerful uterine muscle stimulant, oxytocin plays the key role in
the progression of labour.

Role of corticotrophin releasing hormone (CRH)

CRH secreted by the fetal portion of the placenta into both the maternal
and fetal circulation,

viii. drives the manufacture of placental estrogen,

ix. dictates the timing of the onset of labour
x. promotes changes in the fetal lungs needed for breathing air

CRH is secreted by hypothalamus and regulates output of AcTH

xi. ACTH stimulate both cortisol and DHEA

Increased level of DHEA in response to placental CRH leads to

increase in placental estrogen secretion level

1. Placenta converts DHEA from fetal adrenal gland to

estrogen

7. Describe pregnancy-associated preparation for lactation and the

neuroendocrine regulation of milk production and milk let-down

Lactation

During pregnancy, the mammary glands in the breasts undergo structural

changes to become capable of producing milk
- Increase in the number of alveoli and ducts (milk producing galnds)
 - increase in the number of milk-producing cells called lactocytes

neuroendocrine regulation of lactation involves several hormones

- prolactin
o hormone produced by the anterior pituitary gland
 stimulated by rising level of estrogen
o stimulates milk production.
o The level of prolactin increases during pregnancy and remains high
during lactation
- oxytocin
o produced by the hypothalamus
o stimulates milk let-down, or the release of milk from the mammary
glands.
o released in response to the suckling of the baby,
 triggers the contraction of the muscles around the mammary
glands, allowing milk to flow through the ducts and into the
baby's mouth
- progesterone
o hormone produced by the ovaries
o stimulates abundant alvelorar loblar formation
o suppresses lactation during pregnancy
o The level of progesterone decreases after delivery
 allows lactation to occur
- estrogen
o hormone produced by the ovaries
o promotes the development of the mammary glands during
pregnancy.
o The level of estrogen decreases after delivery,
 allows lactation to occur
- somatomammotropin
o placental hormone that has a structure similar to that of both growth
hormone and prolactin

Prevention of Lactation during Gestation

Most of these changes in the breasts occur during the first half of
gestation, so the mammary glands are fully capable of producing milk by
the middle of pregnancy.

- However, milk secretion does not occur until parturition.

- The high estrogen and progesterone concentrations during the
last half of pregnancy prevent lactation by blocking prolactin’s
stimulatory action on milk secretion.
- Prolactin is the primary stimulant of milk secretion.
o even though the high levels of placental steroids induce the
development of the milk-producing machinery in the
breasts, they prevent these glands from becoming
operational until the baby is born and milk is needed.
- The abrupt decline in estrogen and progesterone that occurs with
loss of the placenta at parturition initiates lactation.

Stimulation of lactation via suckling

Once milk production begins after delivery, two hormones are critical
for maintaining lactation: 

1. prolactin, which promotes milk secretion, and

2. oxytocin, which causes milk ejection.

Milk ejection (milk let down)

: forced expulsion of milk from lumen of alveoli out thrugh the ducts
- release of both of these hormones is stimulated by
neuroendocrine reflex triggered by suckling

Oxytocin release and milk ejection

- milk must be squeezed out of alveoli into the ducts towards the
nipple
o via contraction of specialized myoepithelial cells that
surround each alveolus
- suckling of breast stimulates sensory nerve ending in the nipple
o initates action potential that travels up spinal cord to
hypothalamus
o hypothalamus triggers burst of oxytocin release from
posterior pituitary
- oxytocin in turn, stimulates contraction of myoepithelial cells in the
breast to induct milk ejection

Prolactin release and milk secretion

- suckling triggers stimulation of prolactin secretion
o prolactin is controlled by two hypothalamaic secretion
 prolactin-inhibiting hormone (PIH)
 prolactin-releasing hormone (PRH)
- prolactin concentration remain low due to PIH’s dominant
influence