SM01 Mini2 Flashcards
1
Q
Mitochondria
A
long, ovoid membrane bound organelle found in the cytoplasm
has own DNA
responsible for converstion of food to usable ATP energy
avg. 1000/cell, erythrocytes= 0, more energy demand→ more mitochondria
& distribution vary according to cell type
under basal bodies in ciliated cells to provide ATP for dynein activity in ciliary beating
new ones are made via division, not linked to cell cycle & they do not all divide at the same time
sperm mitochondira are tagged with ubiquitin
2
Q
Outer Mitochondrial Membrane
A
contains porin, large channel forming protein, that are ALWAYS open (only pore in the human body)
thus permeable to molecule 5000Da or less
3
Q
Inner Mitochondrial Membrane
A
surrounds matrix, infoldings create cristae→ increased surface area
contains proteins that carry out oxidative rxns of electron transport chain & ATP synthase
4
Q
Intermembrane Space
A
contains enzymes that use ATP passing out of matrix to phosphorylate other nucleotides
resembles cytosol
pH=7
5
Q
Mitochondrial Matrix
A
inside inner membrane
highly concentrated mix of enzymes for oxidation of pyruvate & fatty acids & those for citric acid cycle
pH=7.5
6
Q
Cristae
A
finger-like projections that cross the mitochondrion formed by the infoldings of the inner membrane
contain ATP transporters that pump new ATP from matrix to intermembrane space
7
Q
mDNA
A
mitochondrial DNA
2-10 circular copies/mitochondrion
<1% of cellular DNA
only 13 out of 615 proteins of mitochondria are coded for on this DNA
8
Q
oxidative phosphorylation
A
9
Q
Lysosome
A
body where lysis occurs
membrane-bound organelle containing digestive enzymes, typically most active at acidic pH (4.8- proton pumps to acidify lumen)
only in cytoplasm, NOT nucleoplasm
degrades proteins, lipids, carbohydrates, DNA, RNA,
size, #/cell, & appearance vary greatly per need
ALWAYS smaller than nucleus in normal cell
material to be degraded is brought in by vesicles that fuse w/lysosome
10
Q
M6P Signal
A
mannose 6 phosphate
signal on proteins to be packaged together to form a primary lysosome
phosphotransferase adds M6P to proteins with lysosomal amino acid sequence with N-linked sugar
11
Q
primary lysosome
A
new lysosome that has just budded from the trans Golgi
contains newly synthesized enzymes
before it receives any material to be digested
“virgin lysosome”
sometimes exicytosed to degrade subtances in the ECF
12
Q
secondary lysosome
A
primary lysosome after it has fused with vesicles containing material to be degraded
13
Q
lysosomal storage diseases
A
>30
most linked to mutation in specifc acid hydrolase
leads to accumulation of partially degraded insoluble metabolite in lysosome
ex. I cell disease & Tay Sachs disease
14
Q
Tay Sachs Disease
A
absence of hexosaminidase A→ cannot breakdown glycolipids (highly prevalent in neurons)→ neurons ballooned w/cytoplasmic vacuoles
destruction of neurons
symptoms: 6 months relentless motor & mental deterioration, and early childhood death (2-3 yrs)
more common in Ashkenazi jews
exception of one time lysosomes are bigger than nucleus
15
Q
autophagy
A
catabolic process involving degradation of cell’s own components via lysosomal machinary
purpose: provide raw materials to sustain life, seen in starvation
16
Q
endocytosis
A
uptake of material into cell by invagination of plasma membrane & internalization of membrane-bound vesicle
function: bring molecules from ECF inside cell &/or retrieve plasma membrane proteins
17
Q
phagocytosis
A
endocytosis in which vesicle contains large food particle
ONLY macrophages & neutrofils
18
Q
proteosome
A
degrades unneeded or damaged proteins by proteolysis that have been tagged with ubiquitin
found in cytoplasm & nucleoplasm
19
Q
Peroxisome
A
small membrane-bound organelle that uses molecular oxygen to oxidze organic molecules
contains enzymes that produce organic molecules, produce hydrgen peroxide & degrade hydrogen peroxide
NOT found in every cell in body
important for liver & kidney function to detoxify bloodstream
rapid responce to change (proliferation when needed)
EM: dark due to stain rxn with catalase enzyme, but otherwise can’t be distinguished
20
Q
fucntions of peroxisome
A
- rid body of toxic substances: hydrogen peroxide, phenols, formic acid, formaldehyde, alcohol
- 1/4-1/2 of ingested alcohol is broken down in perioxisomes
RH2 + O2 → R + H2O2
then catalase used H2O2 to oxidize other hydrocarbons: H2O2 + R’H2 → R’ + 2H2O
- breakdown of long chain fatty acids (>22C) via beta-oxidation→ acetyl-CoA
- NOT coupled with ATP production, but creates H2O2 instead
- synthesis of bile acids in liver
- synthesis of plasmalogens to make myelin→ thus contribution to neurologic symptoms
21
Q
peroxisome formation
A
- de novo: from ER & proteins are imported (-ser-lys-leu-COO-)
- fission: an existing one divids into two
22
Q
aerobic respiration
A
uses oxygen
oxidative phosphorylation takes place in mitochondria
approx. 30 ATP produced
23
Q
anaerobic respiration
A
doesn’t use oxygen
takes place in cytoplasm by glycolysis
makes 4 ATP
24
Q
Mitochondrial fission
A
one mitochondrion splits into two
don’t understand why yet
25
Mitochondrial fusion
two mitochondria fuse into one
don't understand why yet
26
Functions of Mitochondria
1. acetyl-CoA in oxidative phosphorylation in ATP production
2. breakdown of fatty acid molecules to acetyl-CoA
1. must be 22C or less
27
ATP synthase
makes ATP in mitochondrial matrix coupled with protons moving down their electrochemical gradient (intermembrane space to matrix of mitochondria)
found as transmembrane protein in inner membrane of mitochondria
28
mitochondrial targeting sequence
most mitochondrial proteins are still encoded by nuclear genome
always at amino terminus
binds to mitochondrial chaperones before binding to keep it exposed & target it to the mitochondria after ribosome relase
every fourth aa has a positive charge (this is the recognition site for the chaperones
29
mitochondrial disease
1. defective gene in nuclear genome
2. defective gene in mDNA (thus maternally inherited - 15% of total)
30
How Mitochondria Make ATP
1. oxidation of fatty acids & pyruvate to acetyl-CoA, coupled w/reduction of NAD+ & FAD→ NADH & FADH2
2. electrons from reduced coenzymes are transferred via 3 electron transport complexes to O2 & H+ are transported frommatrix to intermembrane space
1. matrix becomes basic (low [proton]) & negatively charged (electric potential)
3. ATP synthase makes ATP coupled with protons moving down their electrochemical gradient (intermembrane space to matrix of mitochondria)
31
proton-motive force
low proton concentration in matrix + negative charge of matrix relative to intermembrane space
32
cardiolipin
double phospholipid (four fatty acid tails)
found mainly in mitochondrial inner membrane
catalyzed by mitochondria themselves
packs tighter than regular phospholipids, better to withstand stress
33
Ubiquination
attaching of ubiquitin to a protein to signal proteosome for degradation
signaled by exposure of string of hydrophobic aa that are normally buried
34
Special Properties of Lysosomes
1. ATP driven proton pump for acidification
2. glycoprotein coat on inner surface to protect it against hydrolysis by its own enzymes
3. transport channels to transport products out of lysosome: amino acids, nucleotides, glucose, etc.
35
Opsinized
"seasoned"
addition of eat me ligand signals attached something to be phagocytosed
ex. antibody coating of bacterium, Fc is eat me signal
36
Autophagosomes
organelle wrapped in ER membrane
destined to fused with lysosome
37
Autolysosome
autosome that has fused with lysosome
38
residual body
remains of secondary lysosome
can be exocytosed or turn into lipofuscin granules (if pigmented)
39
M6P receptor
affinity for M6P at pH=6.5, but not low pH of lysosomes
drops cargo off in lysosomes & recycles
40
I cell disease
defective phosphotransferase→ cannot make M6P targeting signal→ all lysosomal hydrolases are secreted
waste buildup creates "I" (inclusion) cells
symptoms: 6 months failure to thrive & developmental delay, and early childhood death
41
PTS
peroxisomal targeting signal
ser-lys-leu at COOH terminus of protein
42
Zellweger's Syndrome
defect importing proteins to peroxisomes
die soon after birth
homozygous recessive of PTS receptor mutation
43
sER Structure
continuous with rough ER
distal to nucleus
held in place by mictrotubules
more if cell needs to make a lot of lipid or hormones
44
sER Functions
1. lipid biosynthesis
1. all except for cardolipin (made in mitochondria)
2. detoxification rxns
1. more complex molecules than those in peroxisomes, ex. phenobarbital
1. both do ingested alcohol
2. cytochrome p450s (CYP)
3. regulation of Ca2+
1. especially in muscle contraction (sarcoplasmic reticulum)
2. cellular signaling pathways
45
rER Structure
grows out of nuclear envelop
continuous with sER
contains bound ribosomes (they are signaled to attach, but are the same as free ribosomes) on outside of membrane
more of it if cell secretes a lot of protein
held in place by microtubules
46
rER Functions
1. protein synthesis
1. secreted proteins
2. transmembrane proteins (except mitochondrial)
3. lysosomal proteins
2. protein modification
3. sequestration of Ca2+
1. released in signaling pathways
47
Flippases
moves phospholipids from extracellular leaflet to cytoplasmic leaflet
uses ATP
in Golgi
flips phosphatidylserine (negative charge attracts peripheral membrane proteins, ex. PKC) & phosphatidylethanolanine from lumenal (extracellular) to cytosolic face
48
Scramblases
does NOT use ATP
moves phospholipids form one leaflet of a membrane to the other in both directions
movement of two lipid in opposite direction
only found in sER
exist because all new lipids are added to cytosolic leaflet
non-specific to polar head group
makes sER membrane homogenous mixture
49
Lipid transport mechanisms
1. lateral diffusion within a bilayer
2. scramblase assisted translocation between leaflets
3. lipid-transfer protein assisted movement thru cytosol
1. non-specific, bump around from membrane to membrane
4. incorporation in membrane-bound vesicles
50
Secretory Pathway
51
ER signal sequence
usually at amino terminus of protein
usually cleaved in rER lumen by signal peptidase
8 or more non0polar aa at the center
once translated, will be bound by SRP
52
SRP
signal recognition particle
binds to ER signal sequence→ stops mRNA translation→ binds to SRP receptor on rER→ ribosome binds ribosomal receptor on rER & translocator complex→ mRNA translation resumes→ protein pushed through translocon into rER lumen
53
Lipid biosynthesis in sER
newly synthesized lipids inserted into outer leaflet of sER bilayer
made on cytosolic side of sER
54
Floppases
moves phospholipids from cytoplasmic leaflet to extracellular leaflet
uses ATP
55
Chaperones
2 types: hsp70 (heat shock protein 70 in cytoplasm & BiP in ER lumen) & GroEL family
hsp family binds to hydrophobic domains in unfolded proteins
prevent aggregation of unfolded proteins & aid in proper folding
56
Protein membrane insertion
* some use ER signal as transmembrane domain
* translocon springs open to laterally release hydrophobic sequence into membrane
* positively charged aa at either end are flipped so charge faces cytoplasm
*
57
protein modifications in rER
1. N-terminal singal peptide cleavage by signal pepidtase
2. N-linked glycosylation (on asparagine)
1. core= 2x N-acetylglucosamine & v branch of 3 mannose
2. other mannose & glucose added
3. only core survives trimming in Golgi for many
3. formation of disulfide bonds via oxidatioin of cysteine sulfhydral groups
1. stabilizes protein conformation
2. cannot occur in cytoplasm due to reducting atmosphere of glutathione
3. ex. light & heavy chains of antibodies & alpha & beta subunits of insulin receptor
4. - transmembrane domain/+GPI anchor (lipid)
1. covalent bond- still integral protein
5. protein folding by chaperones
1.
58
BIP
binding protein
homologous to HSP70
in rER
correct folding required to leave rER or will tag for degradation
binds to hydrophobic patches as they come through the translocon
59
*N*-glycanase
enzyme that removes N-linked glycosylation for protein ubiquination & degradation
60
Cystic Fibrosis
most common fatal genetic disease in US
death caused by repeated chest infection
mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene
chloirde ion transporter of epithelial cells misfolds→ transporter absent from plasma membrane
chloride imbalance causes cells to secrete less water, cells swell, secretions are very thick
61
secretory pathway
ER (rough or smooth)→Golgi→ secretory vesicle→ plasma membrane
regulatory signal required if bound for elsewhere (lysosome or regulated secretion)
62
SNAREs
(**_S_**oluble **_N_**SF **_A_**ttachment protein **_Re_**ceptor)
v-snares on vesicles; t-snares on target membranes
used for targeting & drive membrane fusion reaction
35 different SNARES, each associated with particular membrane enclosed organelle
snap membranes together so strongly it drives water out→ stalk formation→ hemifusion cytosolic leaflet fused but not lumenal leaflet)→ fusion
63
Rabs
small GTP binding proteins
found on vesicle membranes (different types for direction)
contribute to specificity of docking
binds to tetherin protein on target membrane→ brings SNARES in closer proximity
64
NSF
(N-ethylmaleimide-sensitiven factor)
solubel protein responsible for breaking apart v- & t-SNAREs for recycling with help of SNAPs, uses ATP
65
SNAPs
acessory proteins that aide NSF in recycling of v- &t-SNAREs
66
Botox
uses various forms of botulinum toxin to paralyze muscle activity
cleaves SNAREs for exocytosis of regulated secretory vesicles at neuromuscular junction→ no neurotransmitter release→ no muscle contraction
67
Golgi
membraneous complex of vesicles, vacuoles, & flattened sacs in the cytoplasm
involved in portien modification, intracellular secretion & transport
located on one side of nucleus on top of centrosome (mictrotubule organizing center)
*cis* (closest to ER), *medial* (mulitple sacs), *trans* (faces plasma membrane-exit)
68
modifications in Golgi
* trimming of *N*-linked carbohydrates
* addition of sialic acid to glycoproteins & glyolipids
* aka NANA
* turned black w/ Golgi stain
* onlly carbohydrate group w/ - charge
* give extracellular leaflet of plasma membrane negative charge
* addition of O-linked sugars to serine & threonines
* glycosylation of some lipids, ex. ceramide
69
glycocalyx
cell coat created by thick rim of carbohydrates fanning out from plasma membrane
functions: protection, cellular recognition, slows rate of degradation of secreted & membrane proteins
70
regulated secretion
signal mediated secretion
directed to lysosome or secretory vesicles
ex. insulin, neurotransmitters (acetylcholine, glutamine)
rise of intracellular Ca2+ often triggers release
71
constitutive secretion
secretion without signal mediation
operates continuously
72
M6P signal mechanism
73
phagocytosis mechanism
types of molecules: 0.1-10micrometers in size
74
pintocytosis mechanism
"cell drinking"
each budding vesicle traps a drop of extracellular fluid as it pinches off
types of molecules: indiscriminate
75
receptor-mediated endocytosis
100-500nm
mediated by clathrin coat proteins
receptors for specific proteins cluster in clathrin pits, can have many different receptors in same pit
viruses like to exploit (ex. flu)
types of molecules: insulin, EGF (epidermal growth factor), transferrin, LDL (low density lipoprotein), & polymeric IgA
possible fates: recycling, transcytosis, degradation
76
LDL endocytosis pathway
receptor recycles, ligand degrades
receptor needed for multiple round of endocytosis
ligand is degraded for the cell to use the cholesterol
LDL= low-density lipoprotein, carries cholesterol made in liver through the blood to the body (75% from liver/25% from food)
10-15 min process
proton pump of endosome acidifies vesicle after pinching off→ 6.5 receptor unbinds LDL & pinches off vesicle→ 4.5 merge with lysosome for LDL degradation
77
transferrin endocytosis pathway
ligand & receptor recycle
transferrin blinds to Fe in bloodstream
apotransferrin= no bound Fe
diferric-transferrin= bound to Fe (2Fe3+)
7.2 transferrin receptor has low affinity for apotransferrin, but high for diferric-transferrin→ 6.5 of early endosome Fe release from transferrin & leaves endosome→ transferrin & transferrin receptor are recycled
78
EGF endocytosis pathway
ligand & receptor are degradated by lysosome→ mechanism for down-regulation of signaling pathway
EGFR only cluster in clathrin pits when they are bound to ligand
79
IgA secretion
ligand & receptor are translocated acorss cell & released on the other side
IgA antibodies coming from bloodstream→ bind to receptor on one side of a polarized cell→ travel with receptor in vesicle to other side of cell→ released to ECF on opposite side
80
caveolae
"little caves"
small invaginations of plasma membrane, specialized lipid rafts
many cell types, but neurons have none
abundant in endothelial blood vessel cells (most transcytosing vessels in this cell type)
caveolin: protein that causes invagination
proteins found in them: GPI-linked & proteins w/longer than average transmembrane domains (signaling pathways)
functions: signal transduction & caveolar endocytosis
81
secretory vesicles
regulated ones are often transported intracellularly by dyenin & kinesin on MT to plasma membrane→ actin & myosin take over→ vesicles enmeshed in actin waiting for trigger to release (often rise of intracellular Ca2+)
usually darker on EM due to aggregation of contents
82
Coat proteins
clathrin, COPI, COPII, (caveolin possible 4th)
vesiculation requires coat proteins
water soluble
assemble on membrane face & induce curvature→ serve to cluster membrane cargo proteins→more added to shape membrane into sphere→vesicle pinches off & coat falls off
83
Clathrin
protein coat portein for receptor-mediated endocytosis of plasma membrane
triskelion= unassembled state
lattice= assembled on membrane
84
COPI
protein coat portein for receptor-mediated endocytosis of Golgi
85
COPII
protein coat portein for receptor-mediated endocytosis of ER
86
mitosis
eukaryotic cell division
stages: prophase, metaphase, anaphase, telophase
87
prophase
second stage of mitosis
chromatin condenses to chromosomes, nuclear envelop breaks down, & initiation of mitotic spindle but centrosomes
4X chromosomes, 2n DNA
88
metaphase
third stage of mitosis
chromosomes line up on equatorial plate, spindles bind to kinetichores, centrosomes are at opposite poles
4X chromosomes, 2n DNA
89
anaphase
fourth stage of mitosis
sister chromatids are pulled apart to opposite poles & initiation of cleavage furrow
4X chromosomes, 2n DNA
90
telophase
fifth (last) stage of mitosis
chromosomes unravel to chromatin, nuclear envelop forms, & cytokinesis forming two daughter cells both exactly like the parent cell
2X chromosomes, n DNA
91
actin function in mitosis
formation of contractile ring during cytokensis
92
microtubule function in mitosis
form spindle fibers that bind to kinetochore of chromosomes to pull the sister chromatids apart
minus-end directed motor protein is part of kinetochore protein complex
some motor anchor MT to plasma membrane & pull
other motors push overlapping MT to push the poles apart
93
intermediate filaments function in mitosis
break down nuclear envelope in prophase triggered by phosrylation of nuclear lamins
create two new nuclear envelopes during telophase
94
cohesins
proteins that cross-link two adjacent sister chromatids, multiple along the length of chromosome
critical for chromosome segregation
degraded at start of anaphase
95
condensins
proteins that mediate intramolecular cross-linking to coil DNA during chromosome condensation
96
Taxol
anti-microtubule drug used for cancer treatment
arrest mitotic cells because spindle fibers cannot form so that they perform apoptosis
97
G0
quiescent phase
inactive
neurons stay in this phase permenantly
98
G1
phase most variable in length, dependent on tissue type (bone= 25h)
the differentiated the longer it will stay in this phase
99
S phase
synthesis phase
DNA is replicated, 2n DNA, 4X chromosomes (but they are not condensed yet)
in bone= 8hrs
100
G2
growth and preparartion for mitosis
in bone G2 + mitosis= 2.5-3hrs
101
Preprophase
first stage of mitosis
intranuclear condensation of chromatin & centriole duplication to two centrosomes
102
organelles during mitosis
ER: vesiculates (breaks down) when the nuclear envelope does, reforms during telophase
Golgi: vesiculates (breaks down) when the nuclear envelope does, reforms during telophase
mitochondria, lysosome, & perxoisomes: nothing, but stay out of spindle region (unexplained as of yet)
103
necrosis
premature, accidental death
cells swell & break open, releasing their contents
effects on organism: can damage surrounding tissue & possibly damaging inflammtory response
104
apoptosis
programmed cell death
appearance: round up, appear bigger but are NOT actually bigger
intracellular changes: fragmentation of DNA, shrinkage of cytoplasm, membrane changes→ pieecs bleb off & are phagocytosed by macrophages
effects on organism: no lysis/no inflammation→ no damage to surrounding cells, imperceptible to organism
105
causes of necrosis
mechanical trauma, eposure to toxic agent, burning, freezing, intense UV radiation, anything that quickly depletes ATP of cell (ie hypoxia→ ischemic stroke & heart attack)
106
mitochondrial role in apoptosis
pro-apoptotic BCL-2 family member forms channel in outer mitochondrial membrane releasing cytochrome c (part of the apoptosome) & apoptosis inducing factor
anti-apoptotic BCL-2 family member can bind to these to inhibit channel formation
107
caspases
protein family of proteases that play a role in necrosis, apoptosis & inflammation
cysteine proteases that cleave just C-terminal to asp residues
synthesized as inactive pro-enzymes
cells die in few hours-a day after receiving negative signal or withdrawal of positive signal
108
BCL2
family of proteins that regulate when apoptosis occurs, some pro & some anti
they can regulate each other by forming heterodimers
109
caspase cascade
pro-apoptotic signal→ activation o f initiator caspases→ cleaves & activates effector caspases→ break down of cellular targets
1 molecule of activated caspase can amplify & kill the cell
110
cell survival requirements
produce ATP
be able to maintain barrier to external environment
111
Effects of increased [Ca2+]cytoplasmic
major cause of cellular injury
denatures protein
poisons mitochondria
inhibits cellular enzymes
112
inflammation
protective attempt by organism to remove the injurious stimuli & initiate healing process
characterized by redness, pain, heat, & swelling
caused by: increased blood flow & leakiness of capillaries→ bringing white blood cells to affected tissue
113
hypoxia
oxygen deficiency that causes cell injury & death by reducing oxidative respiration in mitochondria
ex. ischemic stroke & heart attack
causes: ischemia (reduced blood flow), inadequate oxygenation of blood due to cardiorespiratory failure, decrease oxygen carrying capacity (anemia, CO poisoning, severe blood loss)
114
calpains
calcium-activated neutral proteases
activated in brain by high calcium (which can occur during hypoxia b/c neuron can't make enough ATP to maintain strong ion gradient)
cause a lot of damage in brain trauma
115
functions of apoptosis during development
1. deleting unwanted structures (tadpole tail)
2. sculpting specific tissues by ablating fields of cells (developing digits)
3. controlling cell # (50% of neurons eliminated during maturation)
4. eliminating cells during development that are abnormal, nonfunctional, or potentially dangerous (T & B lymphocytes that recognize self)
116
functions of apoptosis during adulthood
1. maintaining homeostatis- cell #
2. eliminating damaged, mutated, or infected cells
3. withdrawal of growth factors
4. viral infection (hopefully before virus can infect surrounding cells)
117
cell loss disorders
AIDS, Alzheimer's, Parkinson's, aplastic anemia, myocardial infarction
118
cell accumulation disorders
CANCER, lupus erythematosus, glomerulonephritis, viral infections
119
triggers for apoptosis
cellular stress (growth factor depletion, free radicals)
viral infection
ionizing radiation/DNA damage
120
intrinsic apoptosis pathway
signal to commit suicide coms from within
growth factor depletion, limited DNA damage, buildup of misfolded proteins in ER
usually uses mitochondrial release of cytochrome c
121
extrinsic apoptosis pathway
signal to commit suicide comes from outside cell
virally infected cell is recognized by death receptor on NK cell→ triggers caspase cascade
122
Phagocytosis of apoptotic cells
1. scramblase in plasma membrane becomes active
2. plasma membrane phospholipids are randomized
1. 50% phosphatidylserine faces extracellularly
2. PS acts as "eat me" signal on bleb
3. macrophages have PS receptor & phagocytose remnants of cell
123
dynamin
protein that cuts the stalk to a clathrin-coated vesicle to release it from the plasma membrane
uses GTP
124
adaptin
proteins tha tbind both clathrin & cytoplasmic tails of certain receptors
125
transcytosis
mechanism for trancellular transport
requires polarized epithelia
used in cells/tissue that move a lot of fluid ie. capillaries & kidney tubules
clathrin-coated & caveolae can transcytose
126
meiosis
cellular division that reduces the number of parent chromosomes in half to produce gametes
127
nondisjunction
failure of homologous chromosomes or sister chromatids to separate during cellular division
128
monosomy
when one chromosome is missing
caused by nondisjunction
gamete has 22 chromosomes instead of 23
129
trisomy
when there is an extra chromosome
caused by nondisjunction
gamete has 24 chromosomes instead of 23
130
oogenesis
primary ooctye (diploid, 4n DNA)→ meiosis I→ secondary oocyte (haploid, 2n DNA) + 1 polar body→ meiosis II→ mature oocyte (haploid, 1n DNA) + 1 polar body
secondary oocytes suspended until fetilization
131
capatication
period of conditioning of sperm cells that occurs in the uterine tubes & lasts 7 hours
glycoproteins & seminal coat of sperm cell are removed by mucosal surface of the tube
after capacitation, sperm can pass freely through corona radiata (outer most covering of oocyte)
132
acrosomal reaction
occurs after binding to the zona pallucida
induced by zona proteins ZP3
release of acrosomal enzymes (acrosin, esterases, neuraminidase) to break through the zona pellucida
133
germ cell
gamete
sperm or oocyte
134
gametogenesis
formation of gametes
involves meiosis & morphological changes
135
prophase I
5 steps: leptotene, zygotene, pachytene, diplotene, & diakinesis
4n DNA
136
leptotene
condensation of chromatin
sister chromatids become connected by Rec8p cohesion complex (specific for meiosis)
pairing of homologous chromosomes initiated
4n DNA
137
zygotene
binding of homologous chromosomes to form tetrad
4n DNA
138
pachytene
crossing-over of different chromatids
creates genetic variation
4n DNA
139
diplotene
disjunction of homologous chromosomes begins
chiasmata (opening between chromosomes) forms
all oocytes rest at this stage
4n DNA
140
diakinesis
condensation concludes
nucleolus disappears & nuclear membrane disintegrates
4n DNA
141
metaphase I
homologous chromosomes line up on equatorial plate
4n DNA
142
anaphase I
homologous chromosomes are pulled to opposite poles
4n DNA
143
meiosis II
separation of sister chromatids
2n DNA→ 1n DNA
144
spermatogenesis
type A spermatogonia (stem cells)→ type B spermatogonia→ mitosis→ primary spermatocyte (diploid, 4n DNA)→ undergo meiosis I→ secondary spermatocyte (haploid, 2n DNA)→ undergo meiosis II→ spermatids (haploid, 1n DNA)→ spermiogenesis→ spermatozoon
145
acrosome
forms from the Golgi→ acrosomal granule→ acrosomal vesicle→ acrosomal cap→ acrosome
forms over anterior portion of nucleus in sperm cells
contains enzymes for acrosome reaction
146
fertilization
200-600 million sperm deposited on external os of cervix
300-500 sperm reach ampullary region
occurs in ampullary region of Fallopian tube (larger outer 1/3- toward ovary)
viability: oocyte (24hrs) & sperm (48hrs)
takes 24hrs
147
endometrium
lining of uterus
divided into two layers: functional & basal
basal contains: spiral artery & base of uterine glands
functional contains: opening of uterine glands, sinusoidal capillaries, & venous lacunae
ALL of functional layer lost during menstration
148
myometrium
middle layer of uterus
contains uterine & arcuate arteries
149
perimetrium
peritoneal covering the outer wall of the uterus
150
stages of fertilization
1. capacitated sperm pass thru corona radiata
2. bind to zona pellucida→ release of ZP3→ release of acrosomal enzymes→ pass thru zona pellucida
3. sperm head attaches to oocyte plasma mebrane & they fuse
4. fast block- 1 minute depolarization of plasma membrane
5. slow block- cortical reaction→ Ca2+ release triggers cortical granules move to plasma membrane
6. zonal rxn- cortical granules released & alter plasma membrane receptors of oocytes & nature of zona pellucida→ prevents polyspermy
151
female pronucleus
nucleus of ovum at fertilization
152
male pronucleus
nucleus of sperm during fertilization after degradation of flagella & flagellar mitochondria
153
corona radiata
originates from cumulus oophorus cells from the follicle
becomes outermost layer around the oocyte & zona pellucida
sperm cells have to have undergone capacitiation to pass freely through this layer
154
zona pellucida
originates from cumulus oophorus cells from the follicle
becomes layer around the oocyte & under teh corona radiata
sperm undergo the acrosome reaction to degrade and pass through this layer
155
corpus albicans
mass of fibrotic scar tissue formed form the shrinking corpus luteum when an oocyte goes unfertilized
corpus luteum will reach its peak at D9 & start to shrink
156
corpus luteum
formed from the remaining granulosa cells of the follicle & theca interna
influenced by leutinizing hormone
develops yellowish pigment & differentiates into lutein cells
secrets estrogen & progesterone that prepares urterine mucosa for implantation
157
corpus luteum of pregnancy
increased growth of corpus luteum after fertilization
grows to 1/3 to 1/2 of ovary size by 3rd month
continues to secrete progesterone through fourth month until the trophoblastic component of the placenta replaces it as the key progesterone secreter
will cause an abortion if removed before the fourth month
158
blastomeres
early mitotic divisions in which the cells become smaller and smaller
until 8 cell stage or 3rd mitotic division
159
compaction
3rd mitotic division or 8-cell
cells form tight junctions between cells
160
morula
day 3
16-cell
formation of inner and outer cell masses
inner cell mass→ embryo proper
outer cell mass→ trophoblast→ placenta
161
blastocele
when morula enters uterine cavity, fluid enters zona pellucida→ when confluent forms single cavity
formation of blastocele marks the evolution of the morula to the blastocyst
162
blastocyst
inner mass= embryoblast
outer mass= trophoblast
cavity in between= blastocele
163
embryoblast
inner cell mass of blastocyst
164
trophoblast
outer cell mass of the blastocyst
cells near embryoblast pole begin the process of implantation on D6
epithelial wall of blastocyst
165
Day 6
zona pellucida has disappeared
L-selectins of trophoblast & carbohydrate receptors on uterine epithelium bind and start implantation
further attachment driven by trophoblast integrins & laminin & fibronectin of the extracellular matrix
166
cytotrophoblast
inner layer of trophoblast
mononucleated cells
mitotic dividing cells that feed the syncytotrophoblast
167
syncytotrophoblast
outer layer of the trophoblast
multinucleated with no clear cellular boundaries
responsible for human chorionic gonadotropin hormone production & secretion used for pregnancy detection by end of 2nd week
168
hypoblast
cuboidal cells from the embryoblast that form need the blastocele
169
epiblast
high columnar cells from the embryoblast that form near the amniotic cavity
170
amniotic cavity
forms as a small cavity in the epiblast & enlarges
171
amnioblasts
epiblast cells adjacent to cytotrophoblast
172
Day 8
formation of cytotrophoblast & syncytotrophobalst from trophobalst
formation of hypoblast & epiblast from embryoblast
173
week of 2's
2nd week
trophobalst forms cytotrophoblast & syncytotrophoblast
embryoblast forms hypoblast & epiblast
extraembryonic layer forms somatic & splanchnic layers
amniontic & definitve yolk sac are formed
174
Day 9
fibrin coagulum forms over uterine epithelim defect at site of embeding embryo
lacunar stage at embryonic pole
formation of primitive yolk sac
175
lacunar stage
vacuoles appear in syncytium & fuse to form lacunae
occurs at embryonic pole
176
primitive yolk sace
aka exocoelomic cavity
@ aembryonic pole, formation of exocoelomic (Heuser) membrane around inner surface of cytotrophoblast + hypoblast
177
sinusoids
syncytotrophobalst erodes endothelial lining of maternal capillaries→ congest & dilate
178
Day 11 & 12
formation of sinusoids & establishment of uteroplacental circulation
chorionic cavity formation
decidua reaction at implantation site
179
extraembryonic mesoderm
derived from yolk sac cells
forms loose connective tissue layer in between cytotrophoblast & exocoelomic cavity
later cells that migrate most caudally from the primitive streak also contribute to this layer
180
chorionic cavity
aka extraembryonic cavity
formed by convergence of cavities in the extraembryonic membrane
surrounds amniotic & primitive yolk sacs
181
extraembryonic somatic mesoderm
extraembryonic mesoderm lining the cytotrophoblast & amnion
182
extraembryonic splanchnic mesoderm
extraembryonic mesoderm that covers the primitve yolk sac
183
Day 13
possible bleeding with increased blood flow to lacunar spaces
primary villi formation
definitive yolk sac formation
trophobalstic lacunae present at abembryonic pole
184
primary villi
cellular columns made of cytotrophoblast cells that porliferate & penetrate into the syncytotrophoblast
185
definitive yolk sac
aka secondary yolk sac
derived from hypoblast cells that migrate along the lining of the exoembryonic mesoderm
smaller than the primitive yolk sac & the exocoelomic cavity
186
chorionic plate
extraembryonic mesoderm lining the inside of the cytotrophoblast after chorionic cavity formation
187
connecting stalk
extraembryonic mesoderm that transverses the chorionic cavity
later becomes the umbilical cord
188
gastrulation
formation of germ layers (endoderm, mesoderm, & ectoderm) during the thrid week
189
primitive streak
forms on the epiblast during D15 or 16
signals start of gastrulation
narrow groove with slight bulging on either side
190
primitive node
slightly elevated area surrounding the primitive pit at the cephalic end of the primitive streak
191
primitive pit
depression at cephalic end of the primitive streak surrounded by the primitive node
192
FGF8
fibroblast growth factor 8
synthesized & secreted by primitive streak & node cells
controls cell migration & specification
193
invagination
inward movement of cells from the epiblast that detach and slip beneath it
194
endoderm
invaginated cells from the epiblast that displace the hypoblast
195
mesoderm
migrated cells from the epiblast that form a layer between the endoderm & ectoderm (previously epiblast)
196
ectoderm
remaining cells of the epiblast on the dorsal surface
197
oropharyngeal membrane
small region of tightly adherent ectoderm & endoderm cells at the cranial end of the trilaminar germ disc
future opening of the oropharyngeal cavity
ruptures in W4, creating communication of foregut with amniotic fluid
198
prechordal plate
thickened region of endoderm in contact with the ectoderm at the cranial end of the primitive streak
anterior to the notochord
stimulates formation of forebrain
199
prenotochordal cells
invaginate at the primitive node & move cranially up the midline until the reach the prechordal plate
intercalculate with the hypobalst for a short time
200
notochordal plate
two cell layer at midline of embryo
201
definitive notochord
formed from notochordal plate as cells migrate to form endoderm & replace hypoblast, notochordal plate proliferates, detaches & forms a tube
solid cord of cells, cranial forms first
underlies neural tube & is signaling center for axial skeleton
considered a type of/part of mesoderm
secrets noggin, chordin, & follistatin to induce neuralization of ectoderm
202
cloacal membrane
similar to oropharyngeal membrane in that it is formed of endoderm & ectoderm w/no interveneing mesoderm
forms at caudal end of disc
forms around D15 or 16
ruptures in W7, creating communication of hindgut with amniotic fluid→ forms anus
203
allantois
aka allantoenteric diverticulum
when cloacal membrane forms
posterior wall of yolk sac forms diverticulum that extends into the connecting stalk
involved in early blood formation & connection to urinary bladder
204
AVE
anterior visceral endoderm
cranial end of trilaminar disc
secretes lefty1 & cerberus→ inhibit nodal→ established cranial end of embryo
205
Day 17
formed trilaminar embryo with definitive notochord
206
laterality
L-R sidedness
accumulation of serotonin (5-HT) on left side→ expression of *MAD*→ restricts *NODAL* expression to left side of primitive streak
if expressed ectopically (on right side), results in laterality defects
207
*Nodal*
activated by FGF8
member of TGF-beta family
inhibited by cerberus & lefty1 in cranial embryo
then restricted to left side caudally by *MAD*
208
sonic hedgehog
expressed more toward the notochord
may serve as midline barrier
ciliary movements are the primitive node sweep high concentrations of shh toward left side
consequence of mutation: holoprosencephaly (forebrain fails to develop into two hemispheres) & synopthalmia (fusion of the eyes)
209
*LEFTY-1*
expressed more toward the lateral plate mesoderm
may serve as midline barrier
210
*SNAIL*
transcription factor restricted to right side of lateral plate mesoderm
others are unknown
211
paraxial mesoderm
cells that migrate from the lateral edges of the primitive node and the cranial edges of the primitive streak
later become divide into the somitomeres & somites
212
intermediate mesoderm
cells that migrate through the midstreak region
later become urogenital system (kidneys & gonads)
connects paraxial mesoderm & lateral plate mesoderm
213
lateral plate mesoderm
cells migrating more caudally
become body wall
214
3rd week
gastrulation
differentiation of cephalic germ cell layers by midweek
notochord formation
secondary villus formation→definitive placental villus
embryo connected to cytotrophoblast shell by connecting stalk
215
4th week
invagination of cells through the primitive streak concludes & primitive streak shrinks & disappears
caudal cells start to differentiate
intraembryonic circulatory system & heart beat
216
secondary villus
extraembryonic mesoderm invades into primary villus growing toward the decidua
early in thrid week
217
definitive placental villus
aka tertiary villus
end of 3rd week
mesodermal cells differentiate into blood cells & blood vessels forming
make connection with blood vessels in mesoderm of chorionic plate & connecting stalks
218
outer cytotrophoblast shell
cytotrophoblast cells penetrate through the synsytotrophoblast & create a thin layer around the trophoblast
function: firm attachment of chorionic sac to maternal endometrium
219
cardiogenic area
mesodermal cells in front of the oropharyngeal membrane
later gives rise to the heart
220
urachus
what the allantois becomes as the bladder enlarges
represented as median umbilical ligament in adults
221
PCD
primary cilia dyskinesia
technically cilia move, but are insufficient or out of synch
50% of cases show transposition of organs in thorax & abdomen due to improper ciliary movement during the 3rd week (shh & FGF8)
222
Kartagener Syndrome
missing dynein arms for ciliary movement
associated triad: sinusitis, bronchiectasis, & complete situs inversus
223
sirenomelia
caudal dysgenesis
loss of mesoderm in lumbosacral region→ fusion of limb buds
associated with maternal diabetes
224
sacrococcygeal teratoma
tumor from the remnants of the primitive streak
has pluripotent cells & various tissue types
225
neural plate
thickening of ectoderm caused by the presence of the notochord & prechordal mesoderm
induced by FGF & repression of BMP4
226
neuroectoderm
cells of the neural plate
227
BMP4
bone morphogenetic protein 4
responsible for ventralizing ectoderm & mesoderm
member of TGF-beta family
high levels induce ectoderm to form epidermis
induces mesoderm to form lateral plate & intermediate mesoderm
inhibited by noggin, chordin, & follistatin cause neural plate induction
low levels induce neural crest formation
228
caudal neural plate
forms hindbrain & spnial cord
dependent on FGF & WNT3a
229
neurulation
process in which the neural plate becomes the neural tube
occurs mid-week 3 thru week 4
\*lengthening of neural plate with lateral to medial movement of cells in plane of ectoderm & mesoderm
230
neural folds
elevated lateral edges of neural plate as it lengthens
231
neural groove
depression between the neural folds
232
neural tube
fusion begins at fifth somite & extends cranially & caudally
233
anterior neuropore
aka cranial neuropore
cranial opening of the neural tube that communicates with the amniotic cavity
closed around day 25
234
posterior neuropore
aka caudal neuropore
caudal opening of the neural tube that communicates with the amniotic cavity
closes around D28
235
neural crest cells
cells from the lateral border or crest of the neurectoderm that undergo epithelial-to-mesenchymal transition
leave neuroectoderm by active migration to mesoderm
236
crest cells from trunk
leave neuroectoderm after closure
1. dorsal pathway: thru dermis→ enter ectoderm through holes in basal lamina→ form melanocytes of skin & hair follicles
2. ventral pathway: thru anterior 1/2 of each somite→sensory ganglia, sympathetic & enteric neurons, & cells of adrenal medulla
237
crest cells from cranium
leave neuroectoderm before closure
cells contribute to craniofacial skeleton, cranial ganglia, glial cells, & melanocytes
238
otic placode
ectodermal thickening formed aroudn the time of neural tube closure
will invaginate to become otic vesicles which develop into structures for hearing & balance
239
lens placodes
ectodermal thickening formed aroudn the time of neural tube closure
will invaginate to become the lenses of the eyes during the 5th week
influences overlying ectoderm to form the cornea
240
splanchnic mesoderm
layer of mesoderm covering the yolk sac
from lateral plate mesoderm
241
somatic mesoderm
layer of mesoderm covering the amnionic sac
from lateral plate mesoderm
242
mesenchyme
loosely organized embryonic connective tissue from any origin
243
intraembryonic cavity
formed by the somatic & splanchnic mesoderm layers
continuous with the extraembryonic cavity on each side of the embryo
W8 gives rise to peritoneal, pleural, & pericardial cavities (secreting membranes)
244
somitomeres
segements of arranged paraxial mesoderm
formation begins cranially and moves caudally
head region: form with segmentation of neural plate into neuromeres & contribute to mesenchyme of the head
occipital region caudally: organize into somites
245
somites
somitomeres occipital region caudally
organized segments of paraxial mesoderm that form rings on either side of the neural tube
3 pairs/day starting at D20 until end of W5 (42-44 pairs)
1st cervical and last 5-7 coccygeal disappear
form axial skeleton
246
segmentation clock
NOTCH goes up in pre-somites cells→ decreases as somites form
boundaries regulated by: retinoic acid (RA) (higher cranially, lower caudally), FGF8 & WNT3a (both higher caudally & lower cranially)
247
FGF2/FGFR
mesoderm cells→ express VEGF-R2
248
VEGF/VEGF-R2
VEGF/Flk1
mesoderm cells→ hemangioblasts
249
VEGF/VEGF-R1
VEGF/Flt1
endothelial coalescences into blood vessels
250
VEGF
vascular endothelial growth factor
directs angiogenesis & vasculogenesis
secreted by mesoderm
251
sclerotome
ventral & medial walls of somite that undergo epitelial→ mesenchymal shift @ W4
will become vertebrae & ribs (tendon, cartilage & bone of that somite)
ventromedial portion of somite induced by NOGGIN & shh from notochord & floor plate of neural tube
PAX1 expression tehn initiates bone & cartilage formation pathway
252
dermatome
forms dermis of the back
cells between dorsomedial & ventrolateral upper edges of somite
retains innervation from its segment
253
myotome
retains innervation from its segment
254
dorsomedial & ventrolateral upper edge somites
precursors to muscle cells
some become mesenchymal again & migrate under dermatome to create dermomyotome
dorsomedial: produces MYF5 (muscle specific) as induced by WNT from dorsal medial tube
255
dermomyotome
creates dermis for skin of back, back muscles, intercostal muscles, & some limb muscles
expresses PAX3 as regulated by WNT from dorsal neural tube
neurotrophin 3 (NT-3) secreted from dorsal region of neural tube directs midportion of dorsal epithelium of somite to become dermis
256
lateral edge somite cells
migrate to parietal layer of lateral plate mesoderm to form muscles of anterior body wall & most of the limb muscles
inhibition of BMP4 & FGF & activation of WNTs from epidermis→ expression of MYOD (muscle specific)→ formation of primaxial & abaxial muscel precursors
257
parietal layer
from lateral plate mesoderm
forms dermis of skin of the body wall & limbs, bone & connective tissue of the limbs, & sterum
scerlotome & muscle precursors that migrate here form costal cartilages, body wall muscles, & limb muscles
258
visceral layer
from lateral plate mesoderm
w/embryonic endoderm, forms lining of gut tube
forms thin serous membranes around each organ
259
mesothelial membrane
thin membranes from mesoderm cells of the parietal layer surrounding intraembryonic cavity
line peritoneal, pleural, & pericardial cavities & secrete fluid
260
angiogenesis
when new blood vessels form from other blood vessels
induced by VEGF/VEGFR signaling
261
vasculogenesis
formation of new blood vessels from blood islands
first blood island formation in W3 in mesoderm surrounding the yolk sac
blood islands arise from hemangoblasts that were once mesoderm cells
262
neural inducers
* noggin, chordin, follistatin
* secreted by notochord to induce neuralization of ectoderm
* cause development of forebrain & midbrain
* WNT3a & FGF
* caudal nerve plate induction to become hindbrain & spinal cord
263
optic vesicle
evaginates form diencephalon→ grows toward lens placode
becomes optic cup: inner layer forms sensory retina & outer layer forms pigmented layer of eye
264
ectoderm derivatives
1. CNS
2. PNS
3. sensory eplithelium EEN
4. epidermis of skin (hair, nail, mammary glands)
5. anterior portion of pituitary gland
6. tooth enamel
7. neural crest cell derivatives
265
D21
fusion of heart tubes into a sinle tube
heart beat at D21 or D22
single atrium & ventricle
266
mesoderm derivatives
1. connective tissue, cartilage, & bone (except head & neck)
2. striated, smooth, & cardiac muscles
3. blood, blood & lymph vessels, & heart
4. kidney cortex
5. gonads & ducts
6. adrenal gland cortex
7. spleen
8. serous membranes lining body cavities
267
vitelline duct
temporary communication of midgut (endoderm) with the yolk sac
268
septum transversum
mass of cranial mesenchyme that gies rise to part od the diaphragm
269
gastroschisis
birth defect in teh abdominal wall
intestines will be on the outside of the body
270
Endoderm derivatives
1. epitelial lining of GI tract
2. epithelial lining of respiratory tract
3. parenchyma of tonsils, thyroid, parathyroids, thymus, liver, & pancreas
4. epithelial lining of urinary bladder & most urethra
5. epithelial lining of tympanic cavity & auditory tube
271
chondrotin sulfate
high levels inhibit migration of neural crest cells to the posterior somite
272
neural crest cell derivatives
1. Connective tissue of face & skull
2. cranial nerve ganglia
3. C cells of thyroid
4. conotruncal septum of heart
5. odontonblast (make dentin of teeth)
6. dermis of face & neck
7. dorsal root ganglia
8. adrenal medulla
9. schwann cells
10. glial cells (enteric)
11. melanocytes
12. forebrain
273
placenta
fetomateranal organ that facilitates nutrient & gas exchange between maternal & fetal compartments
torn from uterine wall & expelled as afterbirth, 30min after child birth
274
chorion frondosum
villous (bushy) chorion of placenta formed by the fetus
villi of decidua basalis
increase in # & size
275
decidua basalis
maternal placental part
functional layer of teh endometrium
W8
276
decidua capsularis
superficial part of decidua that overlies conceptus
277
decidua parientalis
decidua basalis of abembryonic side
278
chorion laeve
smooth chorion
villi of decidua capsularis become compressed & degenerate after W8
279
amniochorionic membrane
fusion of amnion & smooth chorion
due to faster speed of amniotic sac growth compared to chorionic sac
adheres to decidua parietalis
membrane that ruptures during birth
280
placenta septa
aka decidua septa
form during M4 & 5, wedge shape area that form when decidua basalis erodes to enlarge intervillous space
divide placenta into compartments called cotyledons
281
fetal circulation
umbilical arteries= 2, O2 poor blood
umbilical vein= 1, O2 rich blood
282
placental membrane barrier
forms by W16, 4 layers: syncytiotrophoblast, cytotrophoblast, connective tissue (mesenchyme) of villous core, & endothelium of fetal capillaries
after W20, only syncytiotrophoblast & endothelium of fetal capillaries
IgG, T4, T3, & unconjugated steroids can cross
many drugs & viruses & treponema pallidum & toxoplasma gondii
283
maternal IgG
can move through placental membrane barrier
confers fetal immunity to diptheria, smallpox, & measles
adult levels of IgG are not reached until 3
284
erythroblastosis fetalis
aka hemolytic dz of newborn
if fetus is Rh+ & mother is Rh-, mother will create Rh antibodies that will pass to fetus & case hemolysis (rupture of red blood cells)
treated with anti-Rh immunoglobulin
285
hCG
human chorionic gonadotropin
maintains corpus luteum
used to determine pregnancy starting at W2
peaks at W8
286
hCS
human somatomammotropin
allows fetus priority on maternal blood glucose
promotes breast development for milk production
287
estriol
maximum at end of pregnancy
stimulates uterine growth & development of mammary glands
288
treponema pallidum
causes syphilis
can cross from mother to fetus
289
toxoplasma gondii
protazoan that can cross from mother to fetus
causes damage to brain & eyes
290
primitive umbilical cord
W5
connecting stalk (allontois & umbilical vessels), yolk sac, & canal connecting intra & extraembryonic cavities
formed as the amniotic cavity rapidly grows enveloping the connecting stalk & yolk sac stalk
291
function of amnionic fluid
absorbs shock
allows for fetal movement
prevents adherence of embryo to amnion
maintains body temperature of fetus
barrier to infections
\*replaced every 3 hrs, fetus swallow 400mL/day 5M and later
292
hydramnios
aka polyhydramnios
excessive amounts of amniotic fluid
caused by maternal diabetes or congenital abnormalities that prevent fetal swallowing (anencephaly or esophageal atresia)
293
oligohyramnios
insufficient amount of amniotic fluid
fetus can't excrete urine (obstructive uropathy or fetal renal agenesis)
294
