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FOM - WLB > Week 6 Holy - Fertilization, Early Development > Flashcards

Week 6 Holy - Fertilization, Early Development Flashcards

1
Q

What are the functional steps of fertilization?

A
  1. Capacitation
  2. Acrosome reaction
  3. Sperm-egg fusion
  4. Cortical reaction
  5. First cell cycle
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2
Q

What is capacitation?

A

Changes in the sperm that occur furing passage through the female reproductive tract.

  • changes in the plasma membrane
  • increases ability of sperm to fertilize
  • requires 5-6 hours of residency in the female reproductive tract
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3
Q

What are some of the changes that occur in the plasma membrane of sperm during capacitation?

A
  • glycoprotein and lipid content changes
  • cholesterol efflux
  • hyperpolarization
  • unmasking of cell surface receptors that bind the sperm to the egg
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4
Q

What is the acrosomal reaction?

A

Liberation of acrosomal enzymes from the acrosomal vesicle to penetrate the zona pellucida of the egg.

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5
Q

What events have to occur in order for sperm to release the acrosomal enzymes during the acrosomal reaction?

A
  1. pass through egg follicle cells
  2. sperm plasma membrane proteins bind to ZP3
  3. activation of Na+/H+transporters and Ca2+ transporters (increase in sperm cytoplasmic pH)
  4. Ca2+ influx triggers exocytosis of acrosomal vesicle
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6
Q

What two proteins are required for sperm-egg membrane fusion to occur?

A

Izumo and CD9

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7
Q

What are the four steps in sperm-egg membrane fusion?

A
  1. Binding of sperm fertillins with egg integrins
  2. Membrane fusion
  3. Membrane depolarization (fast block to polyspermy)
  4. Ca2+ wave (cortical granule excytosis = slow block to polyspermy)
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8
Q

What occurs in the “fast block to polyspermy”?

A

Fusion of the sperm and egg plasma membranes results in a rapid membrane change that is immediately inhibitory to further fusion with sperm.

  • may be due to membrane depolarization (unsure in mammals)
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9
Q

What occurs in the “slow block to polyspermy”?

A
  • release of free Ca2+ into the cytoplasm of the egg
    • sperm Phospholipase C produces IP3 from phosphatidylinositols
      • opens calcium channels in egg ER
    • triggers cortical granule exocytosis
      • “harden” the zona pellucida
      • prevents the entry of other sperm

a.k.a.: “Zona Reaction”

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10
Q

What does the wave of Ca2+ release following the sperm-egg membrane fusion lead to?

A
  1. Cortical Granule Exocytosis/Zona Reaction
  2. Increased rate of mRNA and protein synthesis in the egg
  3. Destruction of CSF (cohesins)
  4. Relieves inhibition of anaphase promoting complex/APC (stops metaphase II arrest and allows egg to complete meiosis II)
  5. Starts developmental program → 1st cell cycle
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11
Q

What occurs in the first cell cycle?

A
  • Egg completes meiosis II → female pronucleus forms
  • Sperm nucleus decondenses
  • Female & Male pronuclei migrate and converge toward center off egg
    • combined actions of microtubules and microfilaments
  • S-phase of the first mitotic division occurs
  • Prophase begins: chromosomes condense pronuclear envelope breaks down
  • Replication of the sperm centrosome occurs
  • Paternal and maternal chromosomes MINGLE on metaphase plate, anaphase occurs, formation of Two Diploid Cells!
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12
Q

Where does fertilization normally occur?



A

Ampulla of the Oviduct

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13
Q

Approximately how many sperm are present in a normal ejaculate?

A

40 million and 200 million sperm are normally released with each ejaculation

(only a few hundred reach the ampulla of the oviduct)

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14
Q

Roughly what fraction of human sperm in an ejaculate are motile?

A

65%

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15
Q

Roughly what fraction of human sperm in an ejaculate are morphologically normal?

A

50%

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16
Q

What are the lower limits of sperm concentration considered to be acceptable for normal fertility?

A

Male-factor infertillity = total sperm counts fall below 50 million sperm per ejaculate (10-20 million/mL)

with less than 50% motility.

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17
Q

Approximately how many sperm reach the ovulated oocyte in the ampulla of the oviduct?

A

Only a few hundred

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18
Q

What does IVF-ET stand for?

A

In Vitro Fertilization - Embryo Transfer

  • eggs & sperm combined in petri dish and undergo fertilization
  • monitor fertilization microscopically
  • successful embryo replaced into fallopian tube/uterus after appearance of two pronuclei and subsequent cleavage
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19
Q

What does GIFT stand for?

A

Gamete IntraFallopian Transfer

  • 1-4 eggs and about 100,000 sperm are placed directly into the fallopian tube
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20
Q

What does SUZI stand for?

A

Sub-Zonal Insemination

2-10 sperm are injected with a micropipette directly between the zona pellucida and the oocyte plasma membrane

-zygotes/embryos are replaced in the uterus or the fallopian tube

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21
Q

What does ICSI stand for?

A

Intracytoplasmic Sperm Injection

-a single sperm is placed into a micropipet and microinjected directly into the egg cytoplasm

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22
Q

What is a zygote?

A

Fertilized egg cell

A single diploid cell

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23
Q

What is a morula?

A

8-16 cell

2.5 days

cell junctions form

***First cell specialization (inner and outer cells)

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24
Q

Where do the first few cell divisions of the embryo occur?

A

Oviduct

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25
Q

What do the inner cells in a morula become?

A

Inner Cell Mass

-eventually become the embryo proper

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26
Q

What do the outer cells of a morula become?

A

Trophoblast

-later becomes extraembryonic tissues

(including the placenta)

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27
Q

What is compaction?

A
  • tight junctions and gap junctions form (cadherins)
  • cells flatten together to form a tight ball
  • cells become more polarized (apical/basal surface)
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28
Q

When and where does implantation usually occur?

A

When: 6-12 days after fertilization

Where: Usually occurs on the superior posterior wall of the uterine cavity.

(can occur at abnormal sites: abdominal cavity, ovary, or uterine tube)

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29
Q

What happens to the zona pellucida prior to implantation?

A

Hydrolytic enzymes are released by the embryo that degrade the wall of the zona pellucida, allowing the blastocyte to squeeze out, or “hatch.”

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30
Q

What is ectopic implantation?

A

Abnormal implantation.

Blastocyte implants in area other than uterine wall.

ex. abdominal cavity, ovary, fallopian tube, ampulla

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31
Q

What is placenta previa?



A

Implantation close to the mouth of the cervix, resulting in the placenta partially covering the cervical canal.

-can cause hemorrhage during pregnancy and can threaten the survival of the fetus and mother

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32
Q

How does the bilaminar disc form?

A

Inner cell mass flattens and forms a roughly circular disc, composed of two layers.

  • tall columnar cells closest to amniotic cavity = epiblast
  • underlying cuboidal cells = hypoblast
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33
Q

What is the epiblast?

A

Cells in bilaminar disc closest to the forming amniotic cavity.

  • tall columnar cells
  • will eventually give rise to the embryo
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34
Q

What is the hypoblast?

A

Bottom layer of cells in the bilaminar disc.

  • cuboidal
  • Day 9: hypoblast cells enclose space called the primary yolk sac
  • will form extraembryonic structures
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35
Q

When does gastrulation occur?

A

Week 3

36
Q

What is the primitive streak?

A

Thickening formed when epiblast cells migrate toward the midline of the embryonic disc.

Demarcates the anterior-posterior and left-right axies of the embryo.

(primitive groove = valley where epiblast cells fold under in primitive streak)

37
Q

What is the primitive node (Hensen’s node)?

A

Thickening of cells at the cranial end of the primitive streak.

-cells migrate rostrally and form a thick cord of cells called the notochord (inductive force in cell specialization and development)

38
Q

What are the ectoderm derivatives?

A
  • Central and peripheral nervous system
  • epidermis
  • sensory epithelium of ear, nose, & eye
  • pituitary, sebaceous, and mammary glands
  • hair, nails, cutaneous glands
39
Q

What are the endoderm derivatives?

A
  • epithelium of the lung
  • GI tract
  • bladder
  • liver
  • pancreas
40
Q

What are the mesoderm derivatives?

A
  • Paraxial
    • muscles of head, trunk, limbs, axial skeleton, dermis, connective tissue
  • Intermediate
    • urogenital system (gonads)
  • Lateral
    • connective tissue and muscle of viscera, heart and blood cells
    • serous membranes of pleura
    • pericardium
    • peritoneum
41
Q

What are the two main functions of the notochord?

A
  1. lends longitudinal mechanical support to the embryo
  2. serves as a powerful inductive force on the subsequent differentiation of many cell types (prime inducer of nervous system development)

(eventually the vertebral column forms around the notochord)

42
Q

From what layer does the embryo proper arise?

A

Inner Cell Mass

43
Q

What three parts make up the embryo proper?

A

Amnion, yolk sac, and allantois

44
Q

How does the trophoblast become transformed into chorion and placenta?



A

Trophoblast = outer cells in blastocyst

  • Cell proliferation and invasion into uterine wall
  • Forms outer layer of placenta
    • Divided into two layers: overylying Syncytiotrophoblast & underlying Cytotrophoblast

***I don’t know**

45
Q

What is the notochord?

A

thick cord of cells called that have inductive force in cell specialization and development

46
Q

What is the neural plate?

A

The first stage of nervous system formation occurs when epiblast (ectoderm) cells directly overlying the notochord are induced by the notochord to proliferate and to form a thickening called the neural plate.

47
Q

What are neural folds?

A

Areas of the neural plate that buckle and curve around to form a tube.

48
Q

What is the neural tube?

A

Tube completely enclosed by ectoderm

49
Q

How does the neural crest form?

A

Cells detach from the neural tube and actively begin to migrate within the embryo mesoderm.

50
Q

What are the neural crest derivatives?

A
  • Spinal/autonomic/cranial nerve ganglia
  • Schwann cells
  • meninges
  • melanocytes
  • adrenal medulla
  • some craniofacial muscles of the head
51
Q

What are epithelial-to-mesenchymal transitions?

A

EMT

epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types

52
Q

What are mesenchymal-to-epithelial transitions?

A

MET

reversible biological process that involves the transition from motile, multipolar or spindle-shaped mesenchymal cells to planar arrays of polarized cells called epithelia. MET is the reverse process of epithelial–mesenchymal transition (EMT)

53
Q

What is regulative development?

A

Blastomeres initially have similar development potencies, each capable of giving rise to a complete embryo.

The process of differentiation is responsive to environmental signals, which allows the developmental program to respond and adjust to various types of perturbations.

54
Q

What is mosaic development?

A

Cell fate is already assigned during cleavage, and a strict developmental plan is in place, whereby removal of one or more cells results in an incomplete embryo.

Cell fate is usually determined by the differential inheritance of specific factors among daughter cells during cell divisions, in a process called asymmetric cell division.

55
Q

What is the mechanism by which identical (monozygotic) twins are produced?

A

Cells of early embryos fail to adhere together normally, and fall apart.

  • Splitting can occur in:
    • 2-cell embryo → 2 blastocysts, 2 amnions, 2 chorions
    • blastocyst inner cell mass → 2 amnions, 1 chorion
    • after trophoblast formation → 1 amnion, 1 chorion
56
Q

Define totipotent.

A

Totipotent cells can give rise to ALL embryonic and extra-embryonic cell types and structures.

57
Q

Define Pluripotent.

A

Pluripotent cells can give rise to all embryonic cell types and structures, but not extraembryonic stuff.

58
Q

Define multipotent.

A

Multipotent cells can give rise to multiple (but not all) cell types.

59
Q

Define Unipotent.

A

Unipotent cells can give rise to just one type of cell.

60
Q

What is induction?

A

The process were one cell or group of cells changes the developmental fate of another group.

  • defined by distances between cells
    • Paracrine
    • Juxtacrine
    • Autocrine
  • defined by the behavior of cells
    • instructive
    • permissive
  • cells producing signals are the inducers
61
Q

What are morphogens?

A

A substance governing the pattern of tissue development in the process of morphogenesis and the positions of the various specialized cell types within a tissue.

*More precisely, a morphogen is a signaling molecule that alters cell fate.

62
Q

Compare paracrine, juxtacrine, and autocrine signaling?

A
  • Paracrine
    • involves diffusable molecules
  • Juxtacrine
    • involves cell-cell contact
  • Autocrine
    • cells stimulate themselves
63
Q

What is gradient signaling?

A

Cells close to inducer receive greater amounts of signaling factors than cells farther away.

64
Q

What is antagonist signaling?

A

Inducer (agonist) secretes signaling factors and cell opposing inducer (antagonist) sends out inhibitory signal.

65
Q

What is cascade signaling?

A

Inducer secretes signaling factor to nearby cells which in turn send out different signaling factor to nearby cells, which causes those cells to release signaling factors, and so on.

66
Q

What is combinatorial signaling?

A

Two (or more) signals are combined to form a third composite signal, which has a different effect than the two individual signals.

67
Q

How is the dorsal-ventral axis of an embryo determined?

A
  • Notochord induces the ventral floor plate to secrete sonic hedgehog (Shh)
  • Overlying ectoderm induces the dorsal roof plate to secrete BMP
  • The opposing gradients formed instruct the cells in between to express transcription factors (Pax6, Pax7, and NKx6.1) and adopt specific fates
68
Q

How is the left-right axis determined?

A
  • Ciliary cells of the primitive node establish directional fluid flow from right-to-left
    • by all beating in same direction (counterclockwise/leftward)
    • bended cilia is thought to open Ca2+ channels
  • Increases the expression of the signaling molecule “Nodal” on the left side of embryo
    • stimulates production of itself and “Lefty”
      • antagonist to Nodal
    • Nodal also stimulates transcription factor “Pitx2”
69
Q

How is the anterior-posterior (cranial/caudal) axis determined?

A
  • Homeobox (Hox) genes arranged in the same general order on the chromosome as the anterior-posterior axis
    • encode for transcription factors that contain homeodomains (a DNA-binding sequence of 60 AA’s)
    • regulated by retinoic acid which can disrupt normal patterns of Hox gene expression
70
Q

What happens in the Hedgehog signal transduction pathway?

A
  • Patched protein binds to and inhibits smoothened protein
    • allows PKA and Slimb to cleave GLI protein
    • GLI acts as a repressor and no transcritption of Hedgehog-responsive genes occurs
  • Hedgehog binds to Patched protein which activates smoothened protein
    • smoothened inhibits PKA and Slimb
    • uncleaved GLI enters nucleus and activates transcription of Hedgehog-response genes
71
Q

What is Cyclopia?

A
  • Condition due to defective Hedgehog signaling
    • trouble defining midline structures
      • one eye, closely spaced eyes
      • single-nostril
      • midline cleft
      • single central upper incisor
72
Q

What are the “big five” signaling pathways involved in morphogenesis?

A
  1. Transforming Growth Factor (TGF) pathway
  2. Hedgehog pathway
  3. Fibroblast Growth Factor (FGF) pathway
  4. Wnt Pathway
  5. Notch Pathway
73
Q

What are the basic features of TGF pathway?

A
  • TGF-beta Superfamily (Activin, TGF-beta, BMP, and Nodal proteins) ligands
    • Ligand → Receptor II (becomes active)
    • Receptor II → Receptor I → Smad activation → Smad dimerization → Smad4-P acts as transcription factor (transcription or repression)

*Mesoderm & endoderm; osteogenesis; L-R asymmetry

74
Q

What are the basic features of the FGF pathway?

A
  • Fibroblast Growth Factor (FGF) and Epidermal Growth Factor (EGF) = ligands
  • RTKs, FGFR, & EGFR = receptors
  • RTK → GNRP → Ras → MAP kinase cascade → activated transcription factor → stimulates gene expression
75
Q

What are the basic features of the Wnt Pathway?

A
  • Ligand = Wnt
  • Receptor = Frizzled
  • Wnt → Frizzled → active Disheveled inhibits glycogen synthase kinase 3 (GSK-3) → releases and inhibits destruction of beta-catenin → beta-catenin associates with LEF/TCF to become an active transcription factor

*intestinal crypt stem cells, hematopoiesis, neural crest

76
Q

What are the basic features of the Notch Pathway?

A
  • Ligand = Delta
  • Receptor = Notch
  • Delta → Notch → activate protease to cleave Notch → enters the nucleus → Notch activates transcription factor CSL

**Hematopoiesis, neural development, somitogenesis

77
Q

How is cell migration and cell adhesion involved in morphogenesis?

A
  • cell migration is a fundamental part of morphogenesis
  • Epithelial-to-mesenchymal transitions (EMT) and Mesenchymal-to-epithelial transitions (MET) are important events in embryogenesis
    • EMT: regulated by TGF-b, FGF, Wnt, & Notch
    • MET: regulated by BMP
  • Signaling pathways activate the expression of transcription factors like “Snail”
    • regulate genes involved in motility and adhesion
78
Q

How do cadherins function in cell migration, adhesion, and differentiation?

A
  • Selective cell-cell adhesion is mediated by cadherins that are expressed in tissue-specific patterns
    • stop expressing cadherin → break free
    • expression of particular cadherins will dictate where/what cell binds to
  • Cells expressing different cadherins can “sort out” or “re-aggregate”
79
Q

How is the metastatic spread of cancer like the cell movements that occur in embryogenesis?

A
  • Common key features include:
    • Activation of TGF-b, Wnt, or RTK signaling pathways
    • Activation of specific transcription factors (especially Snail family)
    • Changes/inhibition of cadherin expression
    • Modification of the extracellular matrix by matrix metalloproteinases
    • Use of pre-existing tissue structures to guide motility
80
Q

What are the two fundamental characteristics of stem cells?

A
  1. Stem cells can self-renew in order to sustain long-term tissue regeneration
  2. Stem cells are not terminally differentiated, but can give rise to daughter cells that can terminally differentiate
81
Q

What is chemotaxis?

A

Movement of an organism in response to a chemical stimulus.

Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment.

82
Q

What are the usual proliferative potentials of stem cells, progenitor cells, and terminally differentiated cells?

A
  • Stem cells:
    • divide indefinitely
  • Progenitor cells:
    • divide a finite number of times
  • Terminal differentiated cells:
    • unable to differentiate further
    • some able to regain proliferative potential
83
Q

What mechanisms help protect stem cell DNA?

A
  • Use of progenitor cells as an amplifying system keeps the number of stem cells that are needed low
    • number of divisions they need to make is much reduced → reducing the potential for genetic damage
  • Segregate their replicated chromosomes so that the daughter cell that remains a stem cell receives all of the parental chromosome template strands
    • this is called “immortal strand hypothesis”
84
Q

Why does stem cell DNA have to be protected to a greater degree than that of normal somatic cells?

A
  • Stem cells are the reserve cells that are used to replenish tissues and organs.
    • respond to tissue/organ needs
85
Q
A

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