Download Gametogenesis: Spermatogenesis Regulated by Luteinizing

1. Gametogenesis: Spermatogenesis
a. Regulated by Luteinizing Hormone (LH) produced in the anterior pituitary
i. Stimulates testosterone production
ii. Binds to Sertoli cells to promote spermatogenesis
b. Follicle Stimulating Hormone (FSH)
i. Binds to Sertoli cells to stimulate testicular fluid production
c. Primordial Germ Cells (PGC’s) (46, 4n)  gametes
i. 2nd week: formed in the epiblast
ii. Moves to wall of yolk sac
iii. 4th week: migrate to gonads
iv. Remain dormant till puberty
d. PGC’s at puberty differentiate into spermatogonia A (stem cell) in the sex cords
i. Spermatogonia A become clone of cells by meiotic division
ii. The last division of spermatogonia A creates spermatogonia B
e. Spermatogonia B (46, 2n)  mitosis  1° spermatocytes (46, 2n)
f. 1° Spermatocytes  meiosis I  2° spermatocytes (23, 2n)
g. 2° Spermatocyte (23, 2n)  meiosis II  spermatids (23, n)
h. Sertoli cells support and protect the germ cells, providing nutrition, and assists in
release of mature spermatozoa.
2. Spermiogenesis: Morphology of the spermatozoon
a. Four steps for transformation of spermatids into spermatozoa (takes 64 days)
i. Formation of acrosome from Golgi
1. Covers half the nuclear surface
2. Contains acrosin assisting penetration of the egg (zona pellucida)
ii. Condensation of the nucleus
iii. Formation of neck, middle piece, and tail
1. Same structure
as kinocilia (9 + 2
arrangement)
iv. Shedding of most of the
cytoplasm
b. Morphology
i. Head
1. Acrosome and
nucleus
ii. Neck
1. Proximal and
Distal Centrioles
iii. Midpiece
1. Microtubules
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2. Outer dense fibres
3. Mitochondria
4. Annulus
iv. Tail
1. Main piece
a. Microtubules
b. Outer dense fibres
c. Fibrous Sheath
2. End piece
a. Microtubules
c. The mature spermatozoa enters the lumen of the seminiferous tubules and then
‘squeezed’ towards the epididymis
i. Gain full motility in the epididymis
ii. 2-3 mm/min swim speed
3. Gametogenesis: Oogenesis
a. Prenatal maturation
i. 3rd week: PGC’s enter ovary and differentiates into oogonia
ii. End of 3rd Month: undergoes number of meiotic divisions
iii. Become arranged in clusters surrounded by flat epithelial cells (follicle cells)
iv. The majority of oogonia continue to divide by mitosis but
1. Some stop in prophase I and form 1° oocytes
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v. 5 Month: Rapid oogonia production, germ cells in the ovary reach maximum
(about 7 million)
vi. After: Cell death begins
vii. 7th Month: The majority of oogonia have degenerated except for a few near the
surface
viii. All surviving 1° oocytes are stopped in prophase I and most are individually
surrounded by follicular cells = primordial follicle
b. Postnatal maturation
i. Near birth: all 1° oocytes enter into diplotene stage
1. 1° oocytes remain in prophase and do not finish the meiotic division
before puberty is reached (maybe by oocyte maturation inhibitor)
ii. At birth: there are 700 000 – 2 000 000 1° oocytes
1. <500 will be ovulated
2. Can last for 40 years or more
iii. Each ovarian cycle: 15-20 primordial follicles begin to mature  only 1 matures
through all 3 stages – Primary or Preantral  Secondary or Antral 
Preovulatory
1. As 1° oocyte grows follicular cells change from flat to cuboidal and then
proliferate to produce stratified epithelium of granulosa cells, and the
whole unit is called a primary follicle
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2. Granulosa cells rest on basement membrane separating them from
stromal cells = theca folliculi
3. Granulosa cells and oocytes secrete glycoproteins on the surface of
oocytes = zona pellucida
4. As growth continues: follculi organize into theca interna (secretory
cells) and theca externa (fibrous capsule)
5. A fluid filled space forms between the granulose cells and together form
the antrum = secondary follicle (25 mm diameter)
a. Granulosa cells surrounding the oocyte = cumulus oophorus
6. A surge in LH causes the mature secondary follicle to undergo the
Preovulatory growth phase
7. Meiosis I completed and two unequal daughter cells (each 23, 2n) are
formed
a. Secondary oocyte receives most of the cytoplasm
b. First Polar body receives no cytoplasm and lies between zona
pellucida and cell membrane
8. The cell enters meiosis II but stops in metaphase II 3 hours before
ovulation
a. Meiosis II completed only if fertilized
b. Cell degenerates 24 hours after ovulation if not fertilized
4. Ovulation and Fertilization
a. Ovulation
i. FSH stimulates the primordial follicles to grow and mature, and maturation of
granulosa cells
1. Granulosa cells + theca interna cells produce estrogen
ii. LH secreted after estrogen stimulation
1. Stimulates progesterone production in follicular stromal cells and
follicles rupture and ovulation begins
iii. High LH concentration increase collagenous activity surrounding the follicle 
digestion of collagenous fibres surrounding follicle
iv. LH surge cause contraction of the ovary expelling the oocyte with the cumulous
oophorus region out of the ovary
v. Some of the cumulous oophorus rearranges to form the corona radiate
b. Corpus Luteum
i. After ovulation, the ruptured follicle together with cells from the theca interna
forms the corpus luteum by LH influence
ii. The corpus luteum secretes progesterone
iii. Progesterone + Estrogen causes the uterine wall to enter the progestational or
secretory stage which prepares for embryo implantation
c. If no fertilization then…
i. Corpus Luteum reaches maximum development 9 days after ovulation
ii. It shrinks and forms the Corpus Albicans
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iii. Progesterone production decreases and menstrual bleeding occurs
d. If fertilization occurs then…
i. Human chorionic gonadotropin (HCG) prevents degeneration of corpus luteum
ii. Corpus luteum continues to secrete progesterone until the end of 4th month
iii. After 4th month: placenta takes over progesterone secretion
e. Fertilization
i. Occurs in the ampullary region of the uterine tube (widest part and close to
ovary)
ii. Spermatazoa must undergo capacitation (to pass through corona cells) and
acrosome reaction
1. Capacitation is the conditioning period in the uterine tube where the
glycoprotein coat and seminal plasma proteins are removed from the
plasma membrane covering the acrosome
2. The acrosome reaction is induced by zona proteins once bound to zona
pellucida. This causes the release of enzymes to penetrate the zona
pellucida (eg. acrosin)
iii. 3 Phases of fertilization
1. Penetration of Corona Radiata
a. Capacitated sperm passes through the corona radiata
2. Penetration of Zona Pellucida
a. Aided by acrosomal enzymes
b. Cortical reaction: once one sperm comes in contact with the
oocyte surface, the zona pellucida releases lysosomal enzymes
from the cortical granules
3. Fusion of Sperm and Oocyte cell membranes
a. Plasma membranes of egg and sperm fuse  head and tail of
spermatozoa enter the cytoplasm of oocyte, but plasma
membrane is left behind
b. Spermatozoa nucleus  male pronucleus (22 + X or Y)
c. Oocyte completes meiosis II
i. The result is second polar body
ii. And the definitive oocyte  forms female pronucleus
(22 + X)
d. Each pronucleus replicates its own DNA before they fuse
together and form a zygote
5. Cleavage of the fertilized egg, morula, formation of the blastocyst (First week of intrauterine
life)
a. Cleavage
i. After 2 cell stage zygote increases number of cells by mitotic divisions (NOT
increase in mass)
ii. These cells which become smaller with each cleavage are known as blastomeres
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iii. The third cleavage (1  2  4  8 cells) causes the cells to maximize contact
with each other forming a compact ball (compaction process) held by tight
junctions
iv. After 3 days, the compacted 16 cell morula has an inner cell mass and outer cell
mass
1. Inner cell mass  embryo proper
2. Outer cell mass  thophoblast which later contributes to the placenta
b. Blastocyst formation
i. Fluid begins to penetrate zona pellucida into intercellular spaces of the inner
cell mass
ii. The spaces gradually become one singe cavity called the blastocele
iii. Inner mass located on one pole = embyroblast
iv. Outer mass flattens to form wall of blastocyst= trophoblast
v. Zona pellucida disappears  ready for implantation
6. Implantation: Changes in the uterus and on the surface of the blastocyst
a. Wall uterus consists of 3 layers
i. Endometrium – mucosa lining the inside wall
ii. Myometrium – thick layer of smooth muscle
iii. Perimetrium – peritoneal covering lining the outside wall
b. From puberty to menopause, the endometrium undergoes a cycle of 28 days under
hormonal control by the ovary
c. During this menstrual cycle, endometrium passes through 3 stages
i. Proliferative phase – growth under influence of estrogen
ii. Secretory phase (2-3 days after ovulation) – in response to progesterone from
the corpus luteum
1. If fertilization occurs then endometrium assists in implantation and
contributes to formation of placenta
a. Three distinct layers are seen in endometrium
i. Compact layer (superficial)
ii. Spongy layer (intermediate)
iii. Basal Layer (thin)
b. Normally the human blastocyst implants in the endometrium
along the anterior or posterior walls of the uterus
2. If fertilization does not occur then shedding of endometrium marks
beginning of menstrual phase
iii. Menstrual phase
1. Blood from superficial arteries and stuff are shedded
2. 3-4 days during menstrual phase, compact and spongy layer are
expelled from the uterus and only basal layer remains
d. Changes in the surface of the blastocyst
i. …
ii. …
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iii. …
iv. …
7. Development of the blastocyst during the second week
a. 8th day: blastocyst partially embedded into endometrial stroma
i. Trophoblast has two layers
1. Cytotrophoblast: inner layer of mononucleated cells
2. Syncytiotrophoblast: outer multinucleated zone
ii. Inner cell mass or embryoblast differentiates into
1. Hypoblast: cuboidal cells
2. Epiblast: columnar cells
iii. Small cavity appears within the epiblast which enlarges  amniotic cavity
1. Amnioblasts form the roof of the
cavity from epiblast
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b. 9 day: blastocyst more deeply embedded into
endometrium
i. Lacunae form in the syncytiotrophoblast
ii. Primitive yolk sac (exocoelomic cavity)
appears from
1. Heuser’s membrane (single layer of
flat cell) - develops from the
cytotrophoblast
2. Hypoblast
th
th
c. 11 and 12 day: blastocyst is completely
embedded into endometrium, so that the epithelium cell almost entirely covers the hole
in the uterine wall
i. Extraembryonic mesoderm: cells that appear between the inner surface of
cytotrophoblast and outer surface of the exocoelomic cavity (primitive yolk sac)
ii. Extraembryonic Coelom: forms from spaces in the extraembryonic mesoderm
1. Extraembryonic somatopleuric mesoderm – lines the cytotrophoblast
and amnion
2. Extraembryonic splanchnopleuric mesoderm – lines the yolk sac
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d. 13 day: endometrium surface has fully healed
i. Hypoblast produce cells that proliferate and form a new cavity in the yolk sac
1. Secondary yolk sac: as it forms, portions of the exocoelomic cavity
pinch off and become the exocoelomic cyst
2. Extraembryonic coelom  chorionic cavity
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8. Developmental map of the blastocyst (the epiblast fate map)
9. Homeobox genes, determination of body axes
a. HOX genes codes for transcription factors which regulates the morphogenesis
i. There are 39 HOX genes in 4 parallel series
ii. 4 copies on 4 different chromosomes
iii. Genes coding for later events are located upstream
b. 3 axis
i. Craniocaudal (anteroposterior) axis
1. Once the head ends is established, the primitive streak forms caudally,
which is maintained and expressed by nodal, from the TGF-β gene
family
2. Cells at posterior margin of embryonic disc (posterior marginal zone,
PMZ) secretes an activin-like molecule, thus inducing primitive streak
formation
ii. Dorsoventral axis
1. Bone morphogenetic protein-4 (BMP-4) and fibroblast growth factor
(FGF) is secreted throughout the embryonic disc, which ventralizes the
mesoderm into the intermediate and lateral plate mesoderm
iii. Transverse axis
1. Sonic hedgehog expression gets restricted to the left side of the
primitive node by the binding of activin-IIa to its receptor
10. Gastrulation
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a. Occurs during 3rd week of gestation with the formation of the primitive streak on the
surface of the epiblast
i. Cephalic end bulge of the primitive streak is the primitive node
ii. Epiblast cells migrate towards primitive streak and detach from epiblast and slip
into the streak
1. The epiblast cell migrate through the primitive streak and node in
specific patterns which determine their fate (see 8. Epiblast fate map)
iii. The cells invaginate (inward movement), and some cell become endoderm and
others form the mesoderm between the epiblast and newly formed endoderm
iv. The cells remaining in the epiblast  ectoderm
v. As more cells migrate through primitive node, they fuse contact with
extraembryonic mesoderm and become the prechordal mesoderm at the
cephalic end
vi. The cells after become the notochordal plate
b. As hypoblast cells are replaced by migrating endoderm cells moving in the streak, the
notochord proliferates and detaches from endoderm and becomes the definitive
notochord
c. The buccopharyngeal membrane forms the mouth since it is cephalic while the cloacal
membrane forms at the caudal end which forms the anus
i. 16th day: The cloacal membrane appears and the posterior wall of the yolk sac
forms the allantois
d. Migration of cells ceases at 4th week
i. The cranial end starts differentiation sooner
ii. The embryonic plate grows
iii. The primitive streak gets shorter and shorter
e. Primary villi  capillaries created  secondary villi  tertiary villi
i. Capillaries created connect capillaries in the chorionic plate and connecting stalk
ii. Provide nutrition and oxygen
11. Neurulation, derivatives of the ectoderm
a. Middle of 3rd week: Surface ectoderm in midline dorsal to the notchord differentiates
into microdermal cells = neural plate
b. Elongated, slippershaped neural plate expands towards the primitive streak.
c. End of 3rd week:
i. lateral edges of neural plate becomes elevated = neural folds
ii. Depressed midregion forms the neural groove
d. Neural folds approach each other at midline and fuse = neural tube
e. Cephalic and caudal ends of neural tube communicate with amniotic cavity by way of
caranial and caudal neuropores
f. Day 25  closure of cranial neuropore
g. Day 27  closure of posterior neuropore
h. Neuraltion completed and CNS is represented by a closed tubular structure with :
i. A narrow caudal portion = spinal cord
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ii. Broader cephalic portion characterized by dilations = brain vesicles
i. As the neural folds elevate and fuse, cells at the lateral border or crest of the
neuroectoderm begin to dissociate from their neighbors = neural crest
j. Crest cells leave the neural folds after closure of the neural tube and migrate along one
of two pathways :
i. A dorsal pathway through the dermis, where they will enter the ectoderm and
form melanocytes in the skin and hair follicles
ii. A ventral pathway through the anterior half of each somite to become sensory
ganglia, sympathetic and enteric neurons, Schwann cells and cells of the adrenal
medulla.
k. By the time the neural tube is closed, two ectodermal thickenings become visible in the
cephalic region.
i. The otic placodes
1. Forms otic vesicles for hearing and maintenance of equilibrium
ii. The lens placodes
1. 5th week, form the lenses of the eye
l. Derivatives of the Ectodermal Germ Layer
i. CNS and PNS
ii. Sensory epithelium : ear, nose, and eye
iii. The epidermis : hair and nail
12. Differentiation and derivatives of the mesodermal germ
layer
a. Intraembryonic Body Cavity divides the
intraembryonic mesoderm in 3 parts
i. Paraxial mesoderm
1. Beginning of 3rd week paraxial
mesoderm is organized into segments
known as somitomeres
2. Formation proceeds cephalocaudally
3. Somitomeres are further organized
into somites which first arise in the
occipital region (20th day)
4. Divides by transverse grooves into 42-44 pairs of somites
a. 4 occipital
b. 8 cervical
c. 12 thoracic
d. 5 lumbar
e. 5 sacral
f. 8-10 coccygeal
5. The first occipital and 5-6 coccygeal disappear
6. Remaining somites divide into 3 parts
a. Sclerotome – ventromedial part
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i. Bones, cartilage, and ligaments
b. Myotome – middle part
i. Skeletal muscle of chest, abdomen, and limbs
c. Dermatome – dorsal part
i. Dermis
ii. Subcutaneous tissue
ii. Intermediate mesoderm
1. Connects paraxial mesoderm with lateral plate
2. Differentiates into urogenital structures
iii. Lateral plate mesoderm
1. 2 parts
a. Visceral mesoderm – surrounds wall of gut
b. Parietal mesoderm – surrounds intraembryonic cavity of body
wall
b. Derivatives of mesoderm
i. Paraxial
1. Part of skull, muscles, and vertebrae
ii. Intermediate
1. Urogenital system
iii. Lateral
1. Visceral – serous membranes around the organs
2. Parietal – serous membranes, body wall, and limbs
13. Cephalo-caudal and lateral folding. Early differentiation of the endoderm
a. Lateral folding: somites start to rapidly grow laterally which divides and splits the yolk
sac into 3 parts before the gut is formed
i. Intraembryonic part (which becomes gut)
ii. Extraembyonic part (which stays as yolk sac)
iii. Connecting duct (becomes vitelline duct)
b. Cephalo-caudal folding: the curving of the embryo in a sagittal plane
i. 3 parts
1. Foregut – separated from the amnion by buccopharyngeal membrane
a. Created from endoderm
2. Midgut – connected with yolk sac by the vitelline duct
3. Hindgut – separated from the amnion by the cloacal membrane
ii. The buccopharungeal eventually ruptures (4th week) creating an open
connection between amniotic cavity and primitive gut
iii. The cloacal membrane ruptures (7th week) creates an opening for the anus
c. Both types of folding partially incorporate the allantois into the body
d. Derivatives of endoderm
i. Epithelial lining of respiratory tract
ii. Epithelial lining of urinary bladder and urethra
iii. Epithelial lining of tympanic cavity and auditory tube
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iv. Reticular stroma of tonsils and thymus
v. Parenchyma of thyroid, parathyroid, liver, and pancreas
14. Development of the muscular system
a. Skeletal muscle
i. Cell from myotome (middle part of paraxial mesoderm) migrate to their definite
locations and differentiate to myoblast and fuse to form long multi nucleated
fibres
ii. 5th week: myotome cells are divided by intermuscular septum into 2 parts
1. Epimere
a. Dorsal portion
b. Forms extensor muscles
c. Innervated by dorsal ramus
2. Hypomere
a. Ventral portion
b. Forms muscles of limbs and body wall
c. Innervated by ventral ramus
b. Smooth muscle
i. Cells of visceral mesoderm (lower part of lateral plate mesoderm) surround the
gastrointestinal tract (GI tract) and vascular system
ii. Differentiate into smooth muscle cells
c. Cardiac muscle
i. Cell of visceral mesoderm surround the endothelial heart tube
ii. Differentiate to myoblasts and adhere to one another by intercalated dics
iii. Myoblasts develop as in skeletal but don’t fuse, forming the special bundles
called Purkinje fibers
15. Growth of the bones: Increase in length and diameter
a. …
b. …
c. …
16. External appearance of the embryo, development of the fetus, full-term baby
a. 2nd week
i. Bilaminar germ discs
ii. Amniotic cavity
iii. Yolk sac
iv. Extraembryonic mesoderm
v. Extraembryonic coelom
rd
b. 3 week
i. Gastrulation
ii. Parachordal plate
iii. Primitive streak and node
iv. Notochord
v. Trilaminar germ disc (intraembryonic mesoderm, endoderm, and ectoderm)
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c.
d.
e.
f.
g.
h.
i.
j.
vi. 2 mm embryo length
3 and 4th week
i. Neurulation
1. Neural tube
2. Neural crest
ii. Cephalo-caudal and lateral folding
1. Gut
a. Foregut
b. Midgut
c. Hindgut
2. Viteline duct
3. Definitive yolk sac
3rd to 8th week
i. Organogenesis
1. All major organs develop
2. Limbs develop
3. Knee and elbow joints develop
4. Fingers separate
5. Tail disappears
6. 25 mm length of embryo
th
9 week – delivery = fetal period
i. Maturation of tissues and organs
ii. Fast growth of body
rd
3 month
i. Head constitutes half of the length
ii. Eyes found ventrally
iii. Ears found laterally
iv. Limbs are proportional
v. External genitalia can be seen
th
4 month
i. Head a third of length
ii. Eyelids
th
5 month
i. Muscular activity initiates (movements can be felt by mother)
ii. Fetus is covered with fine hair (lanugo hair) on eyebrows and head
6th month
i. Reddish skin
ii. Wrinkled appearance because of lack of underlying connective tissue
iii. Some organs function but the respiratory and CNS have not differentiated
sufficiently and there is little coordination between them
th
7 month
i. 90% survival rate if born at this time
rd
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ii. Subcutaneous fat pads deposit
iii. Maturation of nervous system
iv. 25 cm
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k. 40 week
i. Head is a quarter of length of embryo
ii. 50 cm length of body
iii. 3 – 3.5 kg
l. Premature < 37 weeks
m. Postmature > 40 weeks
17. Fetal membranes, umbilical vessels and cord at full term. Formation of the placenta
18. Twinnings
a. Dizygotic twins (70% of twins) (also called fraternal)
i. Simultaneous fertilization of 2 oocytes and 2 different spermatozoa
ii. The zygotes implant separately in the uterus and grow individually therefore
having their own placentas, amniotic cavity, and chorionic cavity
iii. If placentas are close together fusion might take place, leading to rbc exchange
(erythrocyte mosaicism)
b. Monozygotic twins
i. 1 oocyte is fertilized by 1 spermatozoa
ii. Zygote splits at two cell stage and two separate zygotes develop
iii. Each embryo has own placenta and amniotic cavity, but different chorionic
cavity
iv. If late separation occurs at bilaminar germ disc stage (before formation of
primitive streak), then both embryos will have their placentas, amniotic cavities,
and chorionic cavities together
v. If separation fails to complete = conjoined twins
19. The factors causing malformations
a. Environmental Factors
i. Infections
1. Rubella
2. Toxoplasma
ii. Ionizing radiation
iii. Chemical agents
1. Drugs
2. Vitamins
3. Alcohol
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4. Pollution
iv. Hyperthermia
b. Genetic mutations
i. Dominant, recessive
1. Haemophilia
2. Phenylketonuria
c. Disruptions
i. Vascular accidents
1. Bowel atresis
ii. Amniotic bands
1. Amputation
d. Deformations
i. Mechanical forces
1. Compression
2. Clubfeet (due to compression in amniotic cavity)
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