Lecture 15: Fertilization and Implantation Flashcards
How many cells in the human body?
10 trillion
How many different types of cells in the human body?
250
What do we call cells that can continually renew tissues?
Stem cells
What are the 4 types of stem cells?
- Skin 2. Intestinal 3. Bone marrow 4. Neuronal
3 other names for fertilization?
Syngamy, fecundation and conception
Where does normal fertilization happen within the fallopian tube?
The ampulla region
What are fallopian tubes called in mammals other than humans?
Oviducts
What is active-forward motility?
The way the sperm approaches the egg and then moves from the corona radiata to the zona pellicuda
Describe the stages from sperm coming in contact with corona radiata to entry into ovum (7 steps).
- Release hyaluronidase by breaking down the plasma membrane of sperm to break down the hyaluronate covering the corona radiata cells: corona radiata breaks down and granulosa cells disperse
- Acrosome reaction: zona pellucida induces acrosome membrane of the sperm to break to release acrosin to break down the zona pellicuda: acrosin breaks down ZP1, ZP2, and ZP3 creating a channel through which the sperm can move via active-forward motility
- Sperm fuses to plasma membrane by its tip and then its side
- Fused sperm triggers intracellular Ca2+ wave and oscillations
- Cortical/Zona reaction: egg is activated which causes the cortical granules to release their contents through exocytosis into the perivitelline space
- Contents of cortical granules (1) inactivate ZP3 so it can’t bind to sperm membrane, (2) partially cleave ZP2 which hardens the zona pellicuda so that sperm cannot penetrate = block to polyspermy, and (3) activate PKC and CamKII enzymes that trigger the egg to resume meiosis
- Sperm injects its nucleus, tail, and other organelles into the egg’s cytoplasm, sperm plasma membrane is left behind
- Sperm nucleus decondenses and forms the male pronucleus and sperm tail degenerates
What is the difference between totipotent and pluripotent cells?
Totipotent: cells can become all types of cells in the human body + cells of the placenta Pluripotent: cells can become all types of cells in the human body (but not the placenta cells)
What are the 4 cell stages that are totipotent entirely?
- 2 cell stage 2. 4 cell stage 3. 8 cell stage 4. Morula
Explain the formation of the blastocyst
Fluid filled cavity begins to form due to the blastomeres cells spreading out over each other to prevent fluid from exiting between cells
How many sperm reach the ovum?
Thousands
How are corona radiata cells held together?
Connective tissue of hyaluronic acid
What is the zona pellicuda composed of?
3 glycoproteins: ZP1, ZP2, and ZP3
What do the enzymes released by the sperm after attaching to the ovum precisely break down?
Extracellular adhesion molecules between the cells, not the actual cells
How do the microvilli on the ovum plasma membrane contribute to fertilization?
They ensure the sperm is held firmly in place on the plasma membrane
What are the 2 steps in fertilization that provide a block to polyspermy?
Contents of cortical granules inactivate ZP3 so it can’t bind to sperm membrane + cleave ZP2 which hardens the zona pellicuda so that sperm cannot penetrate
What happens inside the ovum right when the sperm enters? What does this create?
Meiosis resumes at metaphase 2: Kinases (PKC and CamKII) activate other proteins to:
- PKC: pull chromosomes apart on the spindle
- CamKII: half the chromosomes deposited into the second polar body (life not possible without it) and half will form the female pronucleus
Creating the mature oocyte = ovum
Describe restoration of the diploid state following fertilization. When does this occur?
Occurs 6-10 hours post fertilization
- Both the hapoloid male and female pronuclei double their DNA
- The haploid female and male pronuclei come very close next to each other
- The pronuclei’s nuclear membranes dissolve, allowing their chromosomes to mix
- The spindle forms
- Microtubules line up chromosomes on the metaphase plate
- Cytokinesis (24 hours post-fertlization)
What are the 8 developmental transitions?
- Fertilization 2. Induction of the zygotic genome 3. Morula formation 4. Blastocyst formation 5. Implantation 6. Gastrulation 7. Neuralation 8. Organogenesis
What happens during the induction of the zygotic genome
Maternal genes begin to turn off and embryo genes begin to turn on
What is the first embryo stage where there are 2 different cells types? What are they?
Blastocyst: intracellular mass (ICM) and trophectoderm
When does organogenesis start?
8-9 weeks after fertilization
Describe blastocyst formation (3 steps). When does this happen?
4 days post-fertilization
- Outer cells differentiate into trophectoderm and start expressing Na+/L+ ATPase pumps to set up an osmotic gradient for water to flow into the interstitial space (following Na+ out of the cells) to reach equilibrium
- Cell junctions provide structural integrity and prevent water from escaping which allows for bastocoel formation
- Fluid builds up and and pushes inner cell mass to one side (4.5 days post-fertilization)
What are the 3 types of cell junctions created by the blastomeres?
- Occludens (tight) 2. Adherens (intermediate) 3. Desmosomes
When does the fluid filled cavity start to form?
4 days post fertilization
When does the bastocyst hatch out of the zona pellucida?
4.5-5 days post fertilization
When does embryonic implantation occur?
5-9 days post fertilization
What is the ratio of ions pumped by the Na+/K+ ATPase?
3 Na+ out/2 K+ in
What type of cells attach to the endometrial epithelium?
Trophectoderm at the embryonic pole
What type of epithelium is the endometrial epithelium?
Simple: 1 layer
How do the cells of the trophectoderm attach to the endometrial epithelium? 2 mechanisms
- Selectins loosely attach to receptors on mucosa cells
- Integrins strongly attach
Describe the steps of the Na+/K+ ATPase
- 3 Na+ bind to protein channel 2. ATP provides energy to move them against gradient 3. Pi is left bound which causes the channel to change shape 4. 3 Na+ released 5. 2 K+ bind 6. Pi released and channel returns to prior shape 7. 2 K+ released in cell
List the 2 differentiations of the inner cell mass cells in the stroma.
- Columnar cells = epiblast
- Cuboidal cells = hypoblast
What happens to the trophoblast cells once they reach the uterine stroma?
They differentiate into syncytiotrophoblast (=syncytial trophoblast) and cytotrophoblast (=cellular trophoblast)
What types of cells make up the embryonic portion of the placenta?
- Syncytiotrophoblast
- Cytotrophoblast
Draw the embryonic tissues fate map
What is another name for the epiblast?
Primitive ectoderm
What is another name for the hypoblast?
Primitive endoderm
What do the epiblast cells form upon implantation?
The amniotic cavity by giving rising to amnioblasts: think layer of primary ectoderm cells
What do the hypoblast cells form upon implantation?
Heuser’s membrane around the primitive yolk sac: they grow along the cytotrophoblast (along the “old” blastocyst cavity) and become squamous in this process
Heuser’s membrane = primitive endoderm + the ECM it secretes.
What do the syncitiotrophoblast cells form upon implantation? How? Where is it?
It surrounds the embryo entirely and forms trophoblastic lacuna (fluid filled cavities)
What happens to the trophoblastic lacunae at days 8-12?
Syncytiotrophoblast produces digestive enzymes that eat away at arteriole and veniole capillaries which fills up the lacunae with maternal blood
When, where and how does the extraembryonic reticulum form?
Embryonic implantation day 8-12
Between Heuser’s membrane and cytotrophoblasts
The Heuser’s membrane cells (hypoblasts) secrete a gellatenous material: ECM
What proteins in the extraembryonic reticulum?
Fibernectins, laminins
What happens to the epiblast after formation of the embryonic reticulum? How does this affect the embryonic reticulum? What day does this happen on?
It proliferates to form the extraembryonic mesoderm and completely surronds Heuser’s membrane, which can no longer secrete the gellatenous substance in the embryonic reticulum, so it begins to break down and fluid cavities start forming in it and eventually it disappears
Day 12
When does the embryonic reticulum disappear?
Day 12-13
What happens to the extraembryionic reticulum once it disappears?
It becomes the chorionic cavity
Where is the embryo housed at days 12-13?
The chorionic cavity
What forms the yolk sac? What type?
The hypoblast: primary yolk sac
What happens to the primary yolk sac? When?
The inner layer of extraembryonic mesoderm pinches inward to form an 8-like structure that divides the primary yolk sac and pushes it to the Ebb embryonic pole in exocoelomic vesicles
Days 12-13
How is the secondary yolk sac formed?
The cavity that forms closest to the embryonic yolk sac is the secondary yolk sac
Where do the first embryonic blood vesseld form?
The secondary yolk sac: cytotrophoblast villi penetrated by extraembryonic mesoderm
From what is the extraembryonic mesoderm formed? When?
From the epiblast
Day 8-12
How does the syncytiotrophoblast form?
Once the trophoblast cells enter the stroma they proliferate and loose their membrane resulting in a confluent cytoplasm with many nuclei scattered throughout: the syncytiotrophoblast
Implantation of a blastocyst stage embryo first occurs between what two cell types?
Trophectoderm and mother’s uterine epithelium
The chorionic cavity is lined by what type of tissue?
Extraembryonic mesoderm
What are the 2 types of skin stem cells? What does each regenerate?
- Basal layer: regenerates a layer of skin that lacks any other structures of the epidermis
- Hair follicle: regenerates sweat glands, sebaceous glands, hair follicles, etc.
What do the intestinal stem cells regenerate?
Villi/microvilli
How frequently is an entire body regenerated?
Every 7-10 years
What is the ultimate stem cell?
The one cell fertilized embryo
What 2 steps happen with the egg prior to fertilization?
- Ovulation: once a month one of the follicles of the ovary matures and is released from the ovary as a secondary oocyte
- Upon release, it makes its way to the fallopian tube
What type of cells make up the corona radiata?
Granulosa cells
What connects the zona pellicuda with the granulosa cells of the corona radiata? What is the purpose of these?
Gap junctions to facilitate communication between egg and corona radiata
What is the perivitelline space?
The space between the plasma membrane and the zona pellucida
In what stage of meiosis is the secondary oocyte?
Metaphase II
What are the 3 regions of the uterus?
- Corpus: body
- Fundus: portion above the oviduct entry point
- Cervix: narrow portion below corpus that opens into the vagina
What is in between the vagina and the cervix?
The uterine ostium
What are the 3 wall layers of the uterus (from inner to outer)?
- Endometrium
- Myometrium (muscular layer)
- Perimetrium (only a few cell layers thick)
What are the 3 layers of the endometrium during the secretory phase (from inner to outer)?
- Basal layer
- Spongy layer
- Compact layer
What is special about the basal layer of the endometrium?
It has its own blood supply and isn’t sloughed off during menstruation
How many of the thousands of sperm approaching the ovum in the ampulla actually come in contact with the corona radiata?
Hundreds
What is the exact adhesion mechanism between the sperm and the ovum’s plasma membrane?
Still unknown, but here is what we know:
- Sperm’s membrane protein fertilin: alpha/beta subunits that are glycosylated and attached noncovalently (they can move apart)
- Integrins on the ovum’s membrane (look a lot like fertilin)
THEY BIND and pulls them together allowing MEMBRANES TO FUSE!
What is the purpose of blocked polyspermy?
Secures the zygote’s diploid phenotype
Can you discern the female and male pronuclei right after fertlization?
NOPE
What is a blastomere?
Each cell of the 2-cell embryo
When does the 4-cell stage occur?
26 hrs post-fertilization
When does the 8-cell stage occur?
48 hrs post-fertilization
When does the early morula occur? How many cells?
72 hrs post-fertilization
8-12 cells