Fertilization and early development Flashcards
Capacitation-
involves change in the sperm plasma membrane (glycoprotein and lipid content changes) resulting in increased fertilizability
involves change in the sperm plasma membrane (glycoprotein and lipid content changes) resulting in increased fertilizability
Capacitation
Zona pellucida-
Surrounds oocyte; composed of sulfated glycoproteins ZP-1,2, and 3. ZP-2 and ZP-3 form long extracellular filaments that are cross linked by ZP-1.
surrounds oocyte; composed of sulfated glycoproteins ZP-1,2, and 3. ZP-2 and ZP-3 form long extracellular filaments that are cross linked by ZP-1.
Zona pellucida
ZP-3-
sulfated glycoprotein of the zona pellucida that acts a sperm binding receptor. Binding activated sperm plasma membrane H+ and Na+ transporters as well as Ca2+ transporter increasing sperm cytosolic pH and causing influx of Ca++ which triggers exocytosis of the acrosome
sulfated glycoprotein of the zona pellucida that acts a sperm binding receptor. Binding activated sperm plasma membrane H+ and Na+ transporters as well as Ca2+ transporter increasing sperm cytosolic pH and causing influx of Ca++ which triggers exocytosis of the acrosome
ZP-3
Acrosomal reaction-
sperm binds to ZP-3 sulfated glycoprotein of the zona pellucida, H+, Na+, and Ca++ transporters are activated causing exocytosis of the acrosome releasing it’s contents into the oocyte.
sperm binds to ZP-3 sulfated glycoprotein of the zona pellucida, H+, Na+, and Ca++ transporters are activated causing exocytosis of the acrosome releasing it’s contents into the oocyte.
Acrosomal reaction
Izumo-
sperm protein associated with sperm egg plasma membrane fusion
sperm protein associated with sperm egg plasma membrane fusion
Izumo
CD-9-
egg protein associated with sperm/egg plasma membrane fusion
egg protein associated with sperm/egg plasma membrane fusion
CD-9
Zona reaction-
Cortical granule exocytosis- Ca++ released from egg ER by IP3 from sperm/egg plasma membrane fusion causes release of granule contents to extracellular space which inhibits the ability of ZP-3 to bind with sperm and “hardens” the zona preventing polyspermy
Cortical granule exocytosis- Ca++ released from egg ER by IP3 from sperm/egg plasma membrane fusion causes release of granule contents to extracellular space which inhibits the ability of ZP-3 to bind with sperm and “hardens” the zona preventing polyspermy
Zona reaction
Aside from preventing polyspermy, what is another important result of Ca++ increase after fusion-
the egg chromosomes which have been arrested in metaphase 2, continue dividing with the destruction of CSF and activation of APCs. This creates the pro-nucleus of the egg (other half of DNA is exocytosed). Pro-nucleus of sperm is also created and both pro-nuclei enter S phase in preparation for first cleavage division. The pro-nuclei are pushed together by microfilaments and microtubules to for metaphase plate and new unique individual is formed. This is the culmination of fertilization.
oligospermia:
reduced numbers of sperm
asthenospermia:
reduced motility of sperm
teratozoospermia:
altered sperm morphology
Cleavage-
a series of mitotic cell divisions that occur as the embryo moves down the oviduct toward the uterus. (week one)
Blastomeres-
~16 sphereical cells comprising the embryo around day four or five which terms the embryo a morula
~16 sphereical cells comprising the embryo around day four or five which terms the embryo a morula
Blastomeres
Morula-
stage of embryo when it is comprised of ~16 spherical cells
stage of embryo when it is comprised of ~16 spherical cells
Morula
Compaction-
a change in the way blastomeres of the morula interact with eachother. Tight and gap junctions form and cells flatten together to form a ball. Cadherins play an important role here. Also embryo becomes more polarized to for distinct apical and basal surfaces and blastocoel forms. Embyo is now called a blastocyst
a change in the way blastomeres of the morula interact with eachother. Tight and gap junctions form and cells flatten together to form a ball. Cadherins play an important role here. Also embryo becomes more polarized to for distinct apical and basal surfaces and blastocoel forms. Embyo is now called a blastocyst
Compaction
Blastocyst-
the embyo after blastocoel has formed during compaction.
the embyo after blastocoel has formed during compaction.
Blastocyst
Hatching-
at the 6-7 day mark, the blastocoel reaches the uterus and get ready to implant by shedding the zona pellucida by realizing hydrolytic enzymes.
at the 6-7 day mark, the blastocoel reaches the uterus and get ready to implant by shedding the zona pellucida by realizing hydrolytic enzymes.
Hatching
Trophoblast-
the outer cells of the embryo that go on to form the placenta
the outer cells of the embryo that go on to form the placenta
Trophoblast
Syncytiotrophoblast-
formed by the fusion of a portion of the embryonic trophoblast with the epithelial cells of the uterine endometrium. Invades the uterine stroma and contacts maternal circulatory system which begins to nourish the embryo
formed by the fusion of a portion of the embryonic trophoblast with the epithelial cells of the uterine endometrium. Invades the uterine stroma and contacts maternal circulatory system which begins to nourish the embryo
Syncytiotrophoblast
Cytotrophoblasts-
trophoblast cells that do not fuse with the endometrium and divide via mitosis to add cells to the rapidly proliferating syncytiotrophoblast
trophoblast cells that do not fuse with the endometrium and divide via mitosis to add cells to the rapidly proliferating syncytiotrophoblast
cytotrophoblast
Ectopic implantation-
abnormal site of implantation
Human chorionic gonadotropin-
(HCG) secreted by the syncytiotrophoblast to maternal blood stream causing maternal release of estrogen and progesterone to prevent the sloughing of the endometrium and allow maintenance of the pregnancy
(HCG) secreted by the syncytiotrophoblast to maternal blood stream causing maternal release of estrogen and progesterone to prevent the sloughing of the endometrium and allow maintenance of the pregnancy
Human chorinic gonadotropin
Decidual reaction-
trigger by the invasion of the syncytiotrophoblast into the endometrium. Endometrial cells surrounding the embryo begin to accumulate glycogen and lipids.
trigger by the invasion of the syncytiotrophoblast into the endometrium. Endometrial cells surrounding the embryo begin to accumulate glycogen and lipids.
Decidual reaction
Decidual cells-
created from endometrial cells that stock up on lipid and glycogen after invasion of syncytiotrophoblasts. They surround the embryo to form the decidua.
created from endometrial cells that stock up on lipid and glycogen after invasion of syncytiotrophoblasts. They surround the embryo to form the decidua.
Decidual cells
Decidua-
decidual cells surrounding the embryo. One function may be to protect the embryo from the maternal immune system.
Bilaminar disc-
flattening of the inner cell mass to form two layers, the epiblast and the hypoblast. The hypoblast is away from the site of fusion and cells are cuboidal, epiblast is adjacent to the site of fusion and newly forming amniotic sac and cells are columnar
flattening of the inner cell mass to form two layers, the epiblast and the hypoblast. The hypoblast is away from the site of fusion and cells are cuboidal, epiblast is adjacent to the site of fusion and newly forming amniotic sac and cells are columnar
Bilaminar disc
Animal pole-
the inner cell mass, as opposed to the trophoblast
Amniotic cavity-
fluid space between the inner cell mass and adjacent trophectoderm
fluid space between the inner cell mass and adjacent trophectoderm
amniotic cavity
Epiblast-
layer of bilaminar disc adjacent to the amniotic cavity; will eventually give rise to the embryo as well as extraembryonic structures. Identifies the dorsal section of the embryo
layer of bilaminar disc adjacent to the amniotic cavity; will eventually give rise to the embryo as well as extraembryonic structures. Identifies the dorsal section of the embryo.
Epiblast
Hypoblast-
layer of the bilaminar disc that is not adjacent to the amniotic cavity and will only give rise to extraembryonic structures; ie. Yolk sac. Identifies the ventral aspect of the embryo.
Extraembryonic mesoderm-
cells that break free of the primary yolk sac (around day 9) and fill the space between the embryo and the trophoblast. A dense cluster of these cells will give rise to the umbilical chord.
cells that break free of the primary yolk sac (around day 9) and fill the space between the embryo and the trophoblast. A dense cluster of these cells will give rise to the umbilical chord.
Extraembryonic mesoderm
layer of the bilaminar disc that is not adjacent to the amniotic cavity and will only give rise to extraembryonic structures; ie. Yolk sac. Identifies the ventral aspect of the embryo.
Hypoderm
Gastrulation-
mass migration of cells to form three germ layers; ectoderm, endoderm, mesoderm. All are derived from the epiblast.
mass migration of cells to form three germ layers; ectoderm, endoderm, mesoderm. All are derived from the epiblast.
Gastrulation
Primitive streak-
thickening of epiblastic cells to demarcate the left/right and anterio/posterior axis of the embryo
thickening of epiblastic cells to demarcate the left/right and anterio/posterior axis of the embryo
Primitive streak
Mesoderm-
formed by migration of the epiblastic cells through the primitive streak, they displace hypobalstic cells and become the middle layer of the embryo at this point
formed by migration of the epiblastic cells through the primitive streak, they displace hypobalstic cells and become the middle layer of the embryo at this point
Mesoderm
Endoderm-
cells that migrate through the primitive streak and displace hypoblastic cells forming the bottom (ventral) aspect of the embryo
cells that migrate through the primitive streak and displace hypoblastic cells forming the bottom (ventral) aspect of the embryo
Endoderm
Ingression-
the migration of epiblastic cells through the primitive streak to form mesoderm and endoderm
the migration of epiblastic cells through the primitive streak to form mesoderm and endoderm
Ingression
Notochord-
the rostral most epiblastic cells that migrate through the primitive node (Hensen’s node) forming a thick cord that will provide important structural support for the embryo as well as playing a key role in cell differention signaling and the development of the nervous system. The vertebral column eventually forms around the notochord
the rostral most epiblastic cells that migrate through the primitive node (Hensen’s node) forming a thick cord that will provide important structural support for the embryo as well as playing a key role in cell differention signaling and the development of the nervous system. The vertebral column eventually forms around this:
Notochord
Neurulation-
formation of the nervous system, begins 3rd week
formation of the nervous system, begins 3rd week
Neurulation
Neural tube formation-
ectoderm cells directly dorsal to the notochord are induced by the notochord to form the neural plate
ectoderm cells directly dorsal to the notochord are induced by the notochord to form the neural plate
Neural tube formation
Neural plate-
thickening of the ectoderm directly overlying the notochord
Neural folds-
buckling of the neural plate, ~day 18. Neural folds at the cranial end of the notochord enlarge and will eventually become the brain.
buckling of the neural plate, ~day 18; the ones at the cranial end of the notochord enlarge and will eventually become the brain.
Neural folds
Neural tube-
end of the third week; formed by neural folds folding around and fusing to completely enclose the neural tube in ectoderm
end of the third week; formed by neural folds folding around and fusing to completely enclose this structure in ectoderm
Neural tube
Neural crest cells-
population of cells at the lateral border of the neural folds that migrate away from the neural tube to form spinal and autonomic ganglia, Schwann’s cells, the meninges, the adrenal medulla, and melanocytes. Sometimes called the “4th germ layer”.
population of cells at the lateral border of the neural folds that migrate away from the neural tube to form spinal and autonomic ganglia, Schwann’s cells, the meninges, the adrenal medulla, and melanocytes. Sometimes called the “4th germ layer”.
Neural crest cells
Paraxial mesoderm-
one of three types of mesodermal swellings around the third week eventually become 42-44 pairs of somites present around 5th week; become axial skeletal and musculature and associated dermis of the skin
one of three types of mesodermal swellings around the third week eventually become 42-44 pairs of somites present around 5th week; become axial skeletal and musculature and associated dermis of the skin
Paraxial mesoderm
Intermediate mesoderm-
forms two long swellings running rostral-caudal on both sides of the notochord; will become urogenital system
forms two long swellings running rostral-caudal on both sides of the notochord; will become urogenital system
Intermediate mesoderm
Lateral mesoderm-
begins to display fluid spaces that separate the lateral mesoderm into dorsal and ventral wings. The dorsal wing called the somatic mesoderm will help form the lateral and ventral body wall, while the ventral wing called the splanchnic mesoderm will form the gut lining and form mesentery
begins to display fluid spaces that separate the lateral mesoderm into dorsal and ventral wings. The dorsal wing called the somatic mesoderm will help form the lateral and ventral body wall, while the ventral wing called the splanchnic mesoderm will form the gut lining and form mesentery
Lateral mesoderm
Somatic mesoderm-
dorsal wing of the lateral mesoderm; will form lateral and ventral body wall
dorsal wing of the lateral mesoderm; will form lateral and ventral body wall
somatic mesoderm
Splanchnic mesoderm-
ventral wing of the lateral mesoderm will surround the gut and form mesentery
ventral wing of the lateral mesoderm will surround the gut and form mesentery
Splanchnic mesoderm
Coelom-
the space that splits the lateral mesoderm
the space that splits the lateral mesoderm
Coelom
Angiogenesis-
formation of blood vessels (3rd week) in extraembryonic locations, specifically the yolk sac, extraembryonic mesoderm, the connecting stalk, and the chorion. Heart tubes also begin to develop in the embryonic mesoderm cranial to the neural plate at this time; embryonic vessel development progresses so circulation begins at the end of the 3rd week
formation of blood vessels (3rd week) in extraembryonic locations, specifically the yolk sac, extraembryonic mesoderm, the connecting stalk, and the chorion. Heart tubes also begin to develop in the embryonic mesoderm cranial to the neural plate at this time; embryonic vessel development progresses so circulation begins at the end of the 3rd week
Angiogenesis
Embryo folding-
4th week. Embyo begins to fold along two axes; longitudinal and transverse. Gives rise to basic body plan by: 1) converting three flat germ layers into cylindrical endoderm (central/inside), mesoderm (medial) and ectoderm (peripheral/outside) 2) seals off intraemryonic coelom from extraembyonic coelom and 3) rolls endoderm into tubular gut surrounded by mesentery and forms ventral wall
4th week. Embyo begins to fold along two axes; longitudinal and transverse. Gives rise to basic body plan by: 1) converting three flat germ layers into cylindrical endoderm (central/inside), mesoderm (medial) and ectoderm (peripheral/outside) 2) seals off intraemryonic coelom from extraembyonic coelom and 3) rolls endoderm into tubular gut surrounded by mesentery and forms ventral wall
Embryo folding
ECTODERM derivatives:
Epidermis, hair, nails, cutaneous and mammary glands; central and peripheral nervous system
Epidermis, hair, nails, cutaneous and mammary glands; central and peripheral nervous system
ECTODERM derivatives
MESODERM derivatives:
Paraxial: Muscles of head, trunk, limbs, axial skeleton, dermis, connective tissue; Intermediate: Urogenital system, including gonads; Lateral: Serous membranes of pleura, pericardium, and peritoneum, connective tissue and muscle of viscera, heart, blood cells
Paraxial: Muscles of head, trunk, limbs, axial skeleton, dermis, connective tissue; Intermediate: Urogenital system, including gonads; Lateral: Serous membranes of pleura, pericardium, and peritoneum, connective tissue and muscle of viscera, heart, blood cells
Mesoderm derivatives
ENDODERM derivatives:
Epithelium of lung, bladder and gastrointestinal tract; glands associated with G.I. tract, including liver and pancreas.
Epithelium of lung, bladder and gastrointestinal tract; glands associated with G.I. tract, including liver and pancreas.
Endoderm derivates
blastomeres initially have similar development potencies, each capable of giving rise to a complete embryo (vs mosaic development). Development largely depends on induction.
Regulative development-
cell fate is already assigned during cleavage and a strict development plan is in place whereby removal of one or more cells results in an incomplete embryo (not present in humans)
Mosaic development-
the ability of one cell (or some type of signal) to influence the development of another cell. Leads to regulative pattern of development.
Induction-
The first “decision” for an embryonic cell:
Inner cell mass or trophoblast. Regulated by the Hippo signaling pathway. Hippo signaling phosphorylates Yap and also inhibits Tead4 in inner cells. Hippo is inhibited in outer cells stimulating trophoblast formation where Yap and Tead4 are active.
Yap-
associated with trophoblast development
Tead4-
associated with trophoblast development
Second “decision” for inner embryonic cells:
Epiblast or hypoblast. Oct4, Nanog, and Sox2 push cells toward epiblast. Gata positive cells form hypoblast.
Oct 4 -
pushes cells toward epiblast
Nanog-
push cells toward epiblast
Sox2-
push cells towards epiblast
Gata-
push cells towards hypoblast
Third “decision” for inner embryoninc cells-
Ectoderm, endoderm, or Mesoderm. High Oct 4/ low BMP4→ embryonic stem cell self renewal.
High Oct 4/ high BMP4→ mesoderm
Low Oct4/ High BMP4 → ectoderm
Low Oct4/ Low BMP4 → neuroectoderm
Nanog expression inhibits neuroectoderm and neural crest fates
bone morphogenic protein 4. Regulates cell differentiation between ectoderm and mesoderm fates
BMP 4-
fibroblast growth factor; pushes cells to ectoderm; inhibited by Activin, BMP, Wnt; later influence of BMP 4 leads to skin rather than neural
FGF-
lead to endoderm→ liver, lung, pancreas
Activin and Nodal-
can give rise to all embryonic and extra-embryonic cell types and structures
Totipotent-
can give rise to all embryonic cell types and structures
Pluripotent-
can give rise to multiple (but not all) cell types
Multipotent-
can give rise to just one type of cell
Unipotent-
EGA; 4-8 cell stage, most maternal mRNA has been degraded, ~day 3
Embryonic genome activation-
signals that alter cell fate
Morphogens-
cells producing morphogens
Inducers-
induction involving diffusible molecules
Paracrine-
involves cell-cell contact
Juxtacrine-
cells stimulate themselves
Autocrine-
Factor regulating dorsal/ventral axis development-
Sonic hedgehog
Factor regulating left/right asymmetrical axis-
ciliary cells of the primitive node direct Nodal to the left side of the body, Nodal stimulates Lefty which is not strong enough to inhibit Nodal on the left but inhibits whatever Nodal is present on the right
activated by Nodal, it inhibits low amounts of Nodal on the right side
Lefty-
Nodal-
accumulates on the left due to ciliated cells of the primitive node waving the same direction, it activates Lefty which inhibits leftover Nodal present on the right side
responsible for regulating development of anterior/posterior axis (careful, this is cranial/caudal axis in humans)
Hox genes-
in the primitive node, longer exposure to this gives cells a posterior/caudal fate:
Retinoic acid-
The “Big 5” signaling pathways involved in development:
- TGF (transforming growth factor); includes TGF beta, BMP, Activin, Nodal
- Hedgehog
- FGF (fibroblast growth factor)
- Wnt
- Notch
caused by defective Hedgehog signaling
Cyclopia-
mutaions in FGFR3
Achondroplasia and dwarfism-
can promote cancer-especially in the epithelial cells of the colon
Hyperactivity of Wnt-
dispruption of the Notch pathway caused by mutation of Jagged1 gene
Alagille syndrome-
epithelial mesenchymal; TGF-beta, FGF, Wnt, and Notch pathways; important in cell adhesion and migration, regulated by transcription factor Snail
EMT-
mesenchymal epithelial; BMP pathway
MET-
transcription factor regulationg motility and adhesion, represses cadherin, claudin, and occluding resulting in loss of tight junctions and adherins
Snail-
Two drivers of epithelial folding-
cell proliferation and contraction of actin in zonula adherins
Two essential features of stem cells-
- Not terminally differentiated but can give rise to daughter cells that terminally differentiate 2. Can self-renew
rise from stem cells, they are in transit between stem cells and terminally differentiated cells, this is how stem cells are conserved while amplifying their daughter cell numbers. Mitotically active. Can only divide a finite number of times, unlike stem cells.
Progenitor cells-
How are cells “locked in” to a particular pattern of gene expression?
Epigenetic changes involving gene silencing via methylation
when epigenetic changes are “wiped clean” . Ex: imprinting?.
Epigenetic reprogramming-
Two ways stem cell health is maintained:
- The use of progenitor cells 2. Retention of parent DNA strand (less likely to incur mutations)
Inhibitors of DNA binding proteins. They prevent premature differentiation of stem cells. Disfunction can lead to tumorigenesis
Id proteins-
