periods of human development - microanatomymicroanatomy.net/embryology/embryogenesis i-iv...
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Periods of Human Development
Preorganogenic FetalEmbryonic
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Spermatocyte Oocyte
1C1N
2C2N
1C1N
Sperm• 200-300 million ejaculated into female reproductive tract• Survive ≥ 24 hr• Undergo capacitation to become fertile
- requires ≈ 7 hr in female reproductive tract- removes glycoprotein and plasma proteins from plasma membrane
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Development of Oocyte and Follicle
FSH
EstrogenLH secretion Pituitary
Proliferativephase
Uterineendometrium
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Development of Oocyte and Follicle
LH
LH surge
LH surge• Increases levels of maturation promoting factor• Stimulates oocyte completion meiosis I
• 1st polar body formed• Secondary oocyte arrests in metaphase II
• Stimulates ovulation• Stimulates luteal reaction in granulosa and theca cells
• Increases progesterone synthesis• Induces secretory phase in endometrium
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Corpus Luteum
With Fertilization WithoutFertilization
HCG secreted from trophoblastCells degenerate
Corpus luteumof pregnancy formed Corpus albicans
formed
Secretes high levelsof progesterone
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Ovulation
• LH surge• Increases collagenase activity• Increases prostaglandin-induced contractions
of ovary and uterine tube
• Corona radiata forms from cumulus oophorus
• Fertilization occurs in the ampulla within 12-24 hr
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FertilizationCortical reaction• Release of lysosomal enzymes
Acrosome reaction• Release of enzymes (acrosin)• Required for digestion through zona pellucida
Sperm bindZP3 receptors Zona reaction
• Inactivates sperm receptors• Prevents polyspermy
Capacitationrequired for
penetration of corona radiata
Fusion of sperm & oocyte plasma membranes• Involves integrins (oocyte) and disintegrins (sperm)• Stimulates oocytes completion of meiosis II (2nd & 3rd polar body formed)• Sperm mitochondria degraded• Sperm centrioles involved in subsequent cell division
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Fertilization• Restores diploid # chromosomes• Determines sex of embryo
Immediately upon fertilization• Pronuclei form = pronuclear stage• DNA replication occurs 4C, 2N• Chromosomes mix = syngamy• Cleavage occurs 2 cells
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MorulationDay 1-3
• Blastomeres form• Zona pellucida persists• Morula = 16 cell embryo (each cell 1/16 mass of ovum)• Compaction occurs due to formation of tight junctions• Segregation of cells
• Inner cell mass embryo• Outer cell mass trophoblast• Gap junction communication within each group
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Blastocyst formation (day 4-6)
• Zona pellucida degenerates• Blastocyst cavity formed• Embryoblast embryo• Trophoblast placenta
Implantation (day 6-9)
• Trophoblasts invade endometrium• Integrins on trophoblasts bind ECM
• Laminin attachment• Fibronectin migration
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• Ovulation• Fertilization• Cleavage• Morulation• Blastocyst formation• Implantation
Events in Week 1
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With Fertilization• HCG from trophoblast maintains
corpus luteum• Progesterone from corpus luteum
stimulates gravid phase of endometrium
Menstrual Cycle• Menstrual phase ≈ d1-5• Proliferative (follicular) phase• Ovulation ≈ d11-14• Secretory (progestational) phase
begins 2-3 d after ovulation
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Pituitary Regulation of Ovary and Uterus
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Week 2: Formation of Bilaminar Germ Disc
≈ day 7.5
• Embryoblast Epiblast and Hypoblast
• Trophoblast Cytotrophoblast and Syncytiotrophoblast• Cytotrophoblast Syncytiotrophoblast
• Amniotic cavity forms in epiblast
• Decidua reaction: uterine glands secrete glycogen and mucous
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≈ day 9
• Trophoblastic lacunae form in syncytiotrophoblast
• Blastocyst cavity Primitive/primary yolk sac• Cytotrophoblast layer extends around abembryonic pole• Exocoelomic membrane formed
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≈ day 12
• Uteroplacental circulation established by invasion of maternal vasculature• Extraembryonic mesoderm forms• Extraembryonic coelom forms within mesoderm layer
• Coelom separates mesoderm into 2 layers = splanchnic and somatic
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≈ day 13
• Syncytiotrophoblast surrounds embryo and primary villi form• Hypoblast migrates to line inside of primitive yolk sac Secondary yolk sac• Extraembryonic coelom Chorionic cavity
• Extraembryonic somatic mesoderm Chorionic plate• Embryo suspended by connecting stalk
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Ectopic Implantation Sites
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Implantation in Uterine Tube
Implantation in Uterorectal Pouch
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Bilaminar Germ Disc at End of Week 2
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Week 3Gastrulation Forms Trilaminar Germ Disc and Notochord
• Epiblasts migrate• into primitive streak and primitive pit
• Epiblasts differentiate to form• 3 embryonic tissue types
• ectoderm• mesoderm• endoderm
• Notochord
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Formation of Notochord
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Specification of Cranial-Caudal and Dorsal-Ventral Axes
• Anterior visceral endoderm (AVE) present before gastrulation• expresses factors that specify the cranial region
• Nodal expression initiates and maintains the primitive streak
• BMP-4 (hatched area) is expressed throughout embryo• with FGF, BMP-4 specifies the ventral and lateral mesoderm• BMP activity is antagonized (blocked) to induce dorsal mesoderm
• goosecoid, chordin, noggin, follistatin expression by node induce notochord, somites and somitomeres in cranial region• Brachyury (T) expression in mid and caudal regions induces dorsal mesoderm
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Specification of Midline and Left-Right Body Axes
• Notochord expresses sonic hedgehog (SHH) and Brachyury (T) genes at the midline
• Node and primitive streak express FGF8 which controls nodal expression on left side of body
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Embryo at End of Week 3
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Development of Early Placental Villi
• Placental barrier• Syncytiotrophoblast• Basal lamina• Mesoderm• Basal lamina• Endothelial cell
• Where is maternal blood?• Surrounding syncytiotrophoblast
• Where is fetal blood?•Inside villous capillaries
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Week 3
• Notice cranial-to-caudal gradient of development• What is happening during this period?
Gastrulation and notochord formation• How big is the embryo? ≈ 1 mm length
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Week 3
Notochord• Induces ectoderm neural plate• Induces mesoderm somites
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Process of Neurulation
• Edges of neural plate elevate neural folds and neural groove• Folds fuse neural tube• Neural crest
• undergoes epithelial to mesenchymal transition• dissociates from neural tube• migrates throughout body
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Process of Neurulation
• BMP-4 induces ectoderm epidermis• Blocking BMP-4 activity induces formation of neural tissue• Node, notochord & prechordal mesoderm secrete BMP-4 antagonists• Expression of WNT and FGF required to differentiate immature
forebrain/midbrain type tissue into hindbrain
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Week 4
Fusion of neural tube begins in cervical region and proceeds in both cephalic and caudal directions
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Week 4
• Closure of neuropores• d25 and d27• essential to CNS development
• Folding• cephalocaudal• lateral
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Retinoic acid regulates cranial-to-caudal axis
• Controls specification of neural tissue type
• Controls gradient ofHomeobox (Hox) geneexpression
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Mesoderm Differentiation
(Intra-Embryonic)
• Paraxial mesoderm somites (segmented)• Intermediate mesoderm urogenital system (partially segmented)• Lateral plate mesoderm splits
• Somatic continuous with extraembryonic somatic• Splanchnic continuous with extraembryonic splanchnic• Intraembryonic coelom continuous with extraembryonic coelom
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SomiteDifferentiation
• Cranial-to-caudal formationd20-d35
• 42-44 total pairssome degenerate
• Sclerotomebone and cartilage
• Dermomyotome• Dermatome
dermis• Myotome
skeletal muscle
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Regulation of Mesoderm Differentiation
• Notochord: SHH• Neural tube: SHH, WNT, NT3• Ectoderm: BMP-4, WNT• Lateral plate: BMP-4
• Sclerotome: Pax1• Dermomyotome: Pax3• Myotome:
• MyoD (limb & body wall)• Myf5 (back)
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Formation of Blood Vessels
• Vasculogenesis• Form from blood islands
•Angiogenesis• Sprout from existing vessels
• FGF induces hemangioblastblood islandshematopoietic stem
cells and angioblasts• VEGF
• Induces angioblastsendothelial cells
and vessels• Induces angiogenesis
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Cephalocaudal Folding of Embryonic Disc
• Driven by CNS growth• Head & tail fold• Endoderm folded
inside body• foregut• midgut• hindgut
• Yolk sac connected by vitelline duct
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Lateral Folding of Embryonic Disc
• Driven by growth of somites• Lateral plate mesoderm fuses at anterior midline• Vitelline duct persists at midline (in midgut)
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Formation of Endoderm-lined Tube
• Buccopharyngeal and cloacal membranes rupture• Umbilical cord formed
• vitelline duct from midgut• allantois from cloaca of hindgut• blood vessels
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Day 28
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Week 5
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Week 6
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Week 11
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Week 12
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Month 7
Fetus would survive