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241 Cards in this Set

  • Front
  • Back
Hypertrophy
↑(inc.) size of cells
Hyperplasia
↑ (inc.) # of fully differentiated cells

∴ fully fxn cells, but more than usual
Anaplasia
loss of differentiated form and function

refers to degree of differentiation of cells
Regeneration
1:1 replacement by cells of same type

healthy, non-pathogenic
Angioplasty
scrapes off plaque and endothelium lining arterial walls
Endothelium (blood)
Only blood compatible surface in body

clotting occurs when blood contacts any other tissue type
Restenosis
from stenosis -- the abnormal narrowing of a vessel or tubular organ

ex. hyperplasia (excessive smooth muscle proliferation) after angioplasty re-obstructs the vessel, leaving a relatively small lumen through which blood can pass.
Grave's Disease
hyperplasia of thyroid, caused by autoimmune attack producing Ab which bind TSH receptor and turn in constitutively on

symp: protruding eyes, non-pitting edema, fatigue, weight loss w/ high appetite, weakness, tachycardia

treat via surgical removal, anti-thyroid drugs
Metaplasia
Replacement of 1 cell type with another

common in airway & reproductive tract (as a result of chronic environmental insults)
Dysplasia
expansion of immature cells at the expense of location / number of mature cells

last step before cancer

freq. large nuclei, much mitotic activity, pleomorphic, loss of orientation
Pleiotropy
1 gene is responsible for more than one phenotypic characteristic
Neoplasia
loss of growth control (remove growth signals and growth continues)
Benign Neoplasia
loss of proliferation control only

freq. stay as encapsulated tumors, however benign≠harmless
Malignant Neoplasia
cancer

loss of both proliferation & positional control (will invade other tissues and establish tumors there as well)
Normal Cell Proliferation Roles
new blood vessel formation
wound healing
liver regeneration
epithelial cell regrowth
lymphoid cell maintenance
Pathological States -- Fibroblast Proliferation
Fibroplasia
Neurofibromatosis
Psoriasis
Pathological States -- Endothelial Cell Proliferation
Diabetic Retinopathy
Hemangioma (blood vessel tumor)
Pathological States -- Smooth Muscle Cell Proliferation
arteriosclerosis, restenosis, pulmonary hypertension
uterine fibroids
asthma
pyloric stenosis
megaureter
Differentiation vs. Proliferation
Cannot proliferate once differentiated (neurons, cardiac muscle)

Don't proliferate (but can) once differentiated (liver, EC)

High normal turnover/proliferation after differentiation (intestinal crypt cells, bone marrow cells)
Shear Forces
cells will proliferate on agar until a monolayer is formed

application of fresh medium pumped across cells stimulates further growth
Shape Regulates Proliferation
shape gives important input in proliferation decisions; each cell has optimal shape for division
Size Matters for Proliferation
cells must reach requisite size before division occurs

if continually cut before reaching threshold, will not divide.
R-Point
Cells need to make a decision to continue through cell cycle or to exit and enter quiescent state (Go)

*committed step -- last point cell is still sensitive to external environment
Positive Cell Cycle Effectors
peptide growth factors = hormones
Negative Cell Cycle Effectors
interferon
TGF-B
retinoids
heparin sulfates
G1 Checkpoint
Is cell big enough?
Is DNA damaged?
Is environment favorable?
Nutrition status OK?
S Checkpoint
Has the cell gone through mitosis since the last round of DNA replication?
G2 Checkpoint
Is all the DNA replicated?
Is the environment favorable?
M checkpoint
Is spindle formed properly?
Are all chromosomes aligned on the spindle?
MPF
Mitosis Promoting Factor

controls entry into mitosis (through oscillation of concentration and activity)
regulated by phosphorylation/dephos.

2 subunits: cyclin B & CDK1
Go
growth-arrested state

↓ prot. synth
↑ prot. degradation
↓ RNA synth
↓ # polyribosomes
↓ S6 Phos.
flatter shape
R-point response delay
regulated by labil prot. w/ 2h half-lives

long delay indicates presence of inhibitory signals that must be overcome before cell proceeds through cell cycle
Cyclin-CDK connection
monitoring mechanism in cell division

Reg. by multiple phosphorylation events (inhibitory > activating)

Phophatase cleavage of inhibitory P yields rapid activation
Cyclin-CDK Partners
G1: cyclin D --- CDK 4 / CDK 6

G1/S: cyclin E -- CDK2

S: cyclin A -- CDK2

M: cyclin B -- CDK1 (MPF)
Why we need cell death?
a) nec. for normal devlopment (ex. limb dev.)
b) protection against viral infection (ex. prevent viral replication)
c) immune sys. regulation
d) elimination of genetic damage (ex. pot. cancerous cells)
e) ↑ cell death assoc. w/ degenerative neurological diseases (ex. Parkinson's, Alzheimers)
Immune Cell Death (Pathology)
↑ cell death assoc. w/ SCID or AIDS

↓ cell death assoc. w/ autoimmune disease
Types of Cell Death
programmed vs. accidental

apoptosis: programmed -- "death on schedule"

necrosis: accidental; ex. ischemia
Apoptosis
cells do not degenerate randomly, but are broken into cell fragments, then phagocytosed by neighboring epithelial cells

*in normal and diseased tissue, can counterbalance mitosis
Apoptosis (mech)
cell shrinks, chromatin condenses against nuc. membrane, karyorhexis

cell sheds buds (blebs) including nuc. fragments

cell shrinks to single apoptotic body

mito, organelles unaffected
DNA cut into 185 bp fragments

rapid (30-60min)
no inflammatory response
Karyorhexis
breaking up of nucleus in apoptosis

chromatin has already condensed in curved profiles against nuclear membrane
DNA Laddering
cutting of DNA into 185 bp fragments

*represents size of a nucleosome unit

(can see "ladder" pattern when run on gel; necrosis shows a smear)
Ischemic Cell Death
begins w/ swelling of cells and organelles

non-specific DNA degradation

necrosis (lysis) 12-24 hours after death

large inflammatory response as cells are exposed to immune sys
Apoptotic Regulators
Fas/TNF receptor family

Capsases

Bcl-2 family members
Fas L
immunologically privileged sites block B & T cell access (eyes, scrotum/testes, brain)

if Fas R binds Fas L as immune cell tries to cross epithelial tissue, triggers apoptosis
Capsase
(Cytosolic Aspartate-Specific Cysteine Protease family)

zymogen activation cascade, eventually clips nuclear membrane and cytoskeletal proteins

regulated by bcl-2

*executioners
ICE
Interleukin Converting Enzyme
null mutation caspase-3
defective telencephalic (anterior forebrain) development

(cells don't die on schedule)
deletion of caspase 1
↓↓ reduction of Interleukin-1 (IL-1) prod.
Bcl-2 Family
overexpression confers resistance to apoptosis, prolonged B lymphocytes survival

deletion leads to massive B cell apoptosis and loss of thymus and spleen, kidney disease

deletion of pro-apoptotic members (Bad, Bcl-2s, Bax) → hyperplasia lymphocytes, oocytes, and neurons
Pro-apoptotic Bcl-2 members
Bad, Bax, Bak, Bik, Bid, Bcl-Xs
Anti-apoptotic Bcl-2 members
Bcl-2, Bcl-W, McL-1, A1, Ced9, Bcl-XL, E1B 19k, Bhrf1, KSHV ORF16, Lmw5-hl
Human Follicular Lymphoma
Bcl-2 locus at t(14:18) translocation breakpoint

places Bcl-2 prot. just downstream of IgG (↑ expression locus)

leades to prolonged survival of B lymphocytes, oncogenic
Mitochondria in Apoptosis
death signals dephosphorylate Bad, which binds to BCL-Xs on mito. outer membrane

BCL-Xs forms channels, when activated, loss of fxn permeability control, Cytochrome C released to cyto.

Cytochrome C binds Apaf-1 in cyto, cleaves proenzyme capsase9

active capsase 9 accelarates cascade
Apaf-1
apoptotic protease-activating factor 1

binds cytosolic cytochrome C, cleaves pro-enzyme segments from capsase 9
Early Embryonic Development
days 1 → 17

trilayer (3 cell embryo)
Blastomeres
1st 7 days

formed from mitotic cell divisions, no change in size of embryo
Morula
formed at day 3

outer cells (trophoblast) → placenta
inner cells mass → embryo

*ICM cells also for amnion, yolk sac, parts of the placenta. These are the source of ES.
Early Blastocyst
days 3-7

filling of blastocoel → ↑ size, bursts out of zona pelucida ("zona hatching")

*ZP prevents adhearance to fallopian tube walls
Late Blastocyst
days 7-17

begins just before implantation, ends with gastrulation
Early Cleavages
begin in fallopian tube 24-30 hours after fertilization

inside ZP, prevents adherence to fallopian tube walls

48 hours: 8 cell stage (blastomeres)
Embryology
Embryonic Period (weeks 1-8)
Prenatal Period (weeks 9-38)
Teratology
study of abnormal development

birth defects
anomalies
congenital malformations
Gametes
specialized germ cells (♂ & ♀)

haploid (direct result of Meiosis)
Gametogenesis
formation of fully-developed gametes

begins at gonad differentiation in the embryo, ends at fertilization

Mitosis: Amplifies primordial germ cell lines
Meiosis: germ cells undergo meiosis to make gametes
Mitosis
produces all somatic cells
1 S phase -- creates exact copies of chromosome

1 M phase -- duplicated chromosomes attach to spindle, align, separate into 2 complete sets

*parent and daughter cells identical, diploid
Meiosis
only produces gametes
1 S phase

Interphase w/ genetic recombination, followed by 2 divisions

parents diploid, daughters haploid
Spermatogenesis
occurs in seminiferous tubules

*acrosome - specialized golgi
*mid-piece houses mitochondria (GTP → flagella)
*occurs throughout lifetime of male
Spermatogonia
dormant in seminiferous tubules until puberty

multiply by mitosis, mature into primary spermatocytes
Secondary Spermatocytes
products of Meiosis I of primary spermatocytes
Spermatids
4 haploid cells created after completion of Meiosis II
Spermatozoa
mature sperm developing from haploid spermatids

*acrosome is specialized glogi at tip of sperm
*mid-piece houses mitochondria to supply GTP as energy for flagella
*nucleus is highly condensed
Epididymis
long coiled duct on posterior border of testes

continues to ductus (vas) deferens

mature spermatozoa migrate here from seminiferous tubules, stay for storage
Sertoli Cells
line periphery of seminiferous tubules

support / nurture germ cells
Leydig Cells
make testosterone
H-P-O axis
Hypothalamus - Pituitary - Ovary

hormonal "chain of command"
Oogenesis (before puberty)
oogonia --> mature oocytes begins before birth, completed after puberty

oogonia proliferate via mitosis in untero
Primary Oocytes
develop from oogonia

store mRNA, prot, ribosomes for post-fertilization

**reason for maternal inheritance
Follicular Epithelial Cells
ovarian stromal cells form layer of cells surrounding each primary oocyte
Zona Pellucida
specialized extracellular glycoprotein matrix coat

tough cross-linked protein lamina surrounding oocyte

req. for species specific sperm recognition
Cortical Granules
placed near edges of oocyte

secretory granules

upon fertilization, dump enzymes into extracellular space to cross link ZP, create slow block to polyspermy
Primordial Follicle
ZP + single layer follicle cells surround primary oocyte
Primary Oocyte Division
suspended in early prophase I until puberty
Primary Follicle
Granulose Cells

formed from follicular epithelial cells as primary oocytes enlarge in puberty

*respond to pituitary gonadotropin hormones
Ovulation
initiated by FSH (follicle stimulating hormone)

FSH → follicular release of estrogen

10-12 weeks for development from pre-ovulatory (Graafian) follicle

after puberty, one follicle / mo, one oocyte ovulated
MI comp. --> secondary oocyte, disgard polar body
Secondary Ooctye
created from primary oocyte just before ovulation

polar body degenerates

arrested in Metaphase II
(completes MII only if fertilized)
Oocyte Chromosomal Damage
at ovulation, oocytes are 12-55 years of age

* this means there has been plenty of time for environmental factors to damage the chromosomes --> birth defects
Atresia
enormous attrition due to apoptosis of oocytes

2000000 primary oocytes at birth, 400000 at adolescence, 400 ovulated
GnRH
Gonadotropin Releasing Hormone

s: hypothalamus (brain)

t: anterior pituitary

a: synth. & secretion of FSH / LH
FSH
Follicle Stimulating Hormone

s: anterior pituitary

t: ovary

a: stim. ovarian follicle growth, differentiation, and steroidogenesis
LH
Luteinizing Hormone

s: anterior pituitary

t: ovary

a: stimulates ovulation, corpus luteum formation, and steroidogenesis
Estrogens
s: ovary / folllicle cells

t: uterus, vagina, oviduct, mammary glands

a: target growth and differentiation
Progetins
s: corpus luteum

t: uterus, vagina, oviduct, mammary glands

a: target growth and differentiation
Down's Syndrome
Caused by non-disjunction / translocation chromosome 21
Angelman Syndrome
Deletion Ch. 15

severe developmental delay
speech impairment (little use of words), mvmt/balance disorder

unique behavior, happy demeanor (freq. laughter, smiling, easily excitable, flapping hand mvmts.)

delayed head growth, microcephaly by age 2

seizures, onset <3 y
Prader-Willi Syndrome
Deletion Ch 15

developmental delay, poor muscle tone, short stature, small hands and feet
incomplete sexual development

*insatiable appetite
Preimplantation Genetic Diagnosis (PGD)
*blastomere biopsy

can remove 1 or 2 blastomeres from 8 cell stage; test for genetic abnomalities
remaining blastomeres will still form normal embryo / placenta
Early Mitotic Non-disjunction / Translocation
embryo will have 2 or more genetically unique cell lines

*mosaic

phenotypes less severe then total non-isjunction/translocation events
Decidual Cells
endometrial cells around implantation site

day 8-14, ↑ levels glycogen & lipids
develop distinctive polyhedral shape

nourish embryo, provide immunologically privileged status
{prod. prostaglandin E2, ┤T cell, NK cell activation, maternal rejection}
Early Cleavage
24-30h, first mitotic division

48h, 8 cell stage (blastomeres) w/ no change in overall size

*zygote still in ZP (prevents adherence to fallopian tube)
Day 3
Morula forms by compaction, mediated by cadherin

trophoblast --> placenta
inner cell mass (ICM) --> embryo
Day 6
Early Blastocyst attaches

blastocoel (fluid filled cavity) begins to form and increase in size

↑ size puts pressure on ZP, --> zona hatching
Day 7
Late Blastocyst, begins implantation
Days 8-12
Mid-Implantation

syncitiotrophoblasts invade endometrium to nourish embryo

embryo forms bilaminar disc (hypoblast & epiblast)
Days 12-14
Completion of Implantation

syncitiotrophoblast → hCG → C.L.
hCG
ad detectable levels < 10 days after fert.

ensures survival of CL (and ∴ progesterone production, essential to maintenance of pregnancy)
Gastrulation
2 layers become 3

begins in implantation

hypoblast delaminates (moves) and space is filled by rapid, directed movement of epiblast

epiblast forms: endoderm, mesoderm, and ectoderm (3 primordial germ layers)

*takes 2-3 days, perhaps the most important step in development
Spontaneous Abortion of Abnormal Embryos
may appear as late / profuse menses
*33-50% rate (of all pregnancies)
most grossly abnormal

causes early abor:
chromosomal abnormalities (60%)
cleavage problems (25%)
progesterone insufficiency (15%)

*likelihood ↑ w/ ↑ maternal age
Ectopic Pregnancy
blastocyst implants outside of uterus

1/200 (highest in women >35)
95% implant in fallopian tubes (ampulla or isthmus) -- "tubal preg."

ab. pain, tenderness, bleeding, (sim. to appendicitis)
rarely carry to full term, high risk of maternal death
Inhibition of Implantation
large doses estrogen --| blastocyst implantation (Δ progesterone balance disrupts endometrium)
*"Plan B"

RU486 and other drugs work w/ sim. mech
Intrauterine Devices (IUDs)
cause chronic inflammation, interferes w/ implantation
Infertility
the inability to achieve pregnancy after one year of unprotected sex

*affect 8 million American couples, or ~12% of the reproductive age population
Hysterosalpingography (HSG)
dye injected into cervex; should flow through uterus and out of fallopian tubes

can locate blockages potentially preventing fertilization
Causes of Infertility
disruption of any steps between gametogenesis and implantation

♂ 40%
♀ anatomic: 35%
♀ hormonal: 15%
unexplained: 20%
Ovulation Defects
irregular ovulation caused by hypothalamic abnormalities (i.e. Δ GnRH release)

↓ FSH/LH

*stress & extreme athletic activity, eating disorders, hormonal imbalances
Polycystic Ovary Syndrome (PCOS)
apoptotic error → cyst formation

↑ LH : FSH
↑ androgen levels

... leads to chronic weight gain, excessive hair growth, irregular ovulation
♀ Reproductive Tract Abnormalities
anatomical barriers to fertilization / implantation

ex. endometriosis, Pelvic Inflammatory Disease (PID), tubal obstructions, fibroids
Uterine Fibroids
Leiomyomas

benign overgrowths of uterine smooth muscles, project into cavity
Mayer-Rokitansky-Kuster-Hauser Syndrome
complete absence of uterus
Asherman's Syndrome
excessive scar tissue in uterine cavity

*freq. occurs after surgeries such as D & C or myomectomy
D & C
dilation and curettage

scraping out of the uterus

used to remove fibroids (although they will regrow), can cause scarring
Recurrent Pregnancy Loss
3 or more consecutive miscarriages

*only counts "known" pregnancies

may be from a hormone imbalance, ex. failure to maintain progesterone levels
♂ Factors Causing Infertility
azoospermia -- no sperm

oligospermia -- low sperm counts

caused by testicular defects, hormonal abnormalities, high Temp
Varicocele
blown out vein in scrotum, bleed

↑T in scrotum, negatively affects sperm growth and development
Infertility Treatment
1) Diagnose Cause

2) Treat w/ ↓ expensive, ↓ invasive therapy appropriate

3) Progress until successful treatment found
Order of Infertility Treatment
Surgical correction of reproductive tract defects

1) oral drugs (clomiphene citrate)
2) clomiphene w/ intrauterine insemination (IUI)
3) injectable drugs (hMG, FSH) and IUI
4) IVF
Clomiphene Citrrate
+cheap, oral
--| estrogen receptors in hypothalamus

→ FSH / LH prod, stim follicle growth

one week after last dose, hypothalamus senses estrogen threshold for pituitary LH surge --> ovulation
hMG

Human Menopausal Gonadotropins
injection

req. follicle size monitoring (via ultrasound)
→ multiple dominant follicles, ↑ P (mult. births)

when mature follicles detected, ovulation triggered w/ hCG (mimics LH surge)
equal FSH/LH, derived from urine of postmenopausal women

*used: women w/ no luck w/ clomiphene c. & women w/ ↓ FSH / LH
FSH

(Follicle Stimulation Hormone)
subcutaneous injection

stim. ovaries to prod. mult. follicles and oocytes

*used: PCOS patients (high LH/ low FSH levels)
GnRH

Gonadotropin Releasing Hormone
pump, releases GnRH @ 90 min. intervals ('mimic' hypothalamus)

*used: anovulatory b/c of abnormal FSH/LH release
hCG

(Human Chorionic Gonadotropin)
one subcutaneous injection at end of treatment to induce ovulation (comes 36-72 h later)

*used: triggers ovulation
IUI

(Intrauterine Insemination)
*used: ↓ ♂ infert. fact., ♀ w/ cervical mucus abnormalities (wrong pH)

perf. w/ ovulatory induction (↑ efficacy)
24-36 hours after LH surge induced

*sperm washed (mimics capacitation)
IVF

(In Vitro Fertilization)
gonadotropins induce ovulation for egg retrieval (laproscopic proc. w/ ultrasound)

mature eggs incubated w/ washed sperm, early cleavages obs. w/in 2-3 days

normal embryos implanted into uterus
ICSI

(Intracytoplasmic Sperm Injection)
"zona drilling"

*No membrane fusion
*No normal Ca++ wave

using pipet, sperm injected directly into cytoplasm of oocyte
Embryo Transfer (IVF)
2-3 days after retrieval, 1-4 best embryos transf. to uterus

cath. inserted through vagina, cervix, and into uterus

ultrasound helps placement of embryos in uterus

woman lays in bed for several hours, 4-6 hours later discharged

*progesterone given to max. chances of good uterine lining
Homotypic Cell-Cell Interactions
involve a single cell type

ex. formation of epithelial layers
Heterotypic Cell-Cell Interactions
involving 2 or more cell types

ex. mesenchymal-epithelial interactions
Homophilic Molecular Interactions
self-association

ex. Uvumorulin (mouse embryo compaction)
Heterophilic Molecular Interactions
involving 2 or more macromolecules
Matrix Crossbridging
cell surface receptors bind extracellular matrix mol. in multivalent manner

ex. basal lamina between epithelium and mesenchyme
Dynamic Interactions
making and breaking of contacts

ex. neural crest w/ fibronectin (migration)
Stabilized adhesions
redistribution of surface receptors following primary interactions

ex. neuromuscular jxn
Tissue-Specific Adherence
homotypic

dissociated cells adhere preferentially w/ cells of same tissue type

can mix cells of multiple types, will reassemble into tissue specific aggregates
Mesenchymal-Epithelial Interactions
heterotypic

* if mammary gland epithelia is combined w/ salivary mesenchyme, will appear to be a salivary gland, but will produce milk

development involves ingrowth of epithelial cells into underlying mesenchyme

mesenchyme : morphology
epithelium : fxn
Compaction of the Early Mouse Embryo
homophilic

blastomeres held together by ZP

Ca++ dependent adhesion at 8 cell stage

Ab against uvomorulin (a cadherin) --| compaction, blastomeres continue to divide, do not form blastocyst
Binding of Metastatic Cells to Basement Membranes
matrix cross-bridging

2` tumor as conseq. of metastasis

a. binding to basement membrane
b. secretion of degradation enzymes
c. movement into adjacent tissues

laminin binds itself, t. IV collagen, heparan sulfate proteoglycan, and entactin, *cell surface receptors

*metastatic cells ↑ binding to laminin-coated surf. & ↑# receptors

Ab against laminin --| metastases
Interaction of Neural Crest Cells with Fibronectin
dynamic

originate along dorsal border of neural tube
at closure, n. crest cells break loose from epithelium, migrate

--> give rise to many tissues (peripheral neurons, schwann cells, pigment cells, connective tissue)
*cells follow pthwys lined w/ large adhesive glycoprotein fibronectin

Ab against fibronectin interrupt interaction w/ crest cells, blocks migration
Neuromuscular Junction
stabilized
EC
endothelial cells

surround lumen in arterial walls -- only blood-compatible surface in body
ECM
extracellular matrix

underlies EC monolayer in vessel wall
IEL
internal elastic lamina

tough, fenestrated elastin-containing lamina
Intima
portion of vessel wall composed of EC and ECM
Arteriosclerosis
response to injury to the arterial wall (from hypertension, hypercholesterolemia, hyperlipidemia, surgery, ...)

platelet aggregation followed by deposits of granular products & growth factors
--> SMC hyperplasia/proliferation

*may eventually occlude vessel
Marfan's Syndrome
elastin cross-linking defect (usually from defective fibrillin)
fibrillin forms "spring" connecting elastin fibers

constant pressure changes in large vessels causes progressive stretching out of wall --> aneurysm
Pemphigus
autoimmune

Ab to desmoglein (a cadherin)

blistering disease; desmosomes and hemidesmosomes in skin are destroyed
Glansmann's thrombasthenia
defective integrin

clotting disease (integrins essential for platelet aggregation)

freq. fatal by 2-3 years
Metastatic Cancer
fibronectin, laminin, MPPs
Arteriosclerosis
multiple-proteoglycans, CAMs, etc., ...
Scurvy
vitamin C def. --| cross-linking

collagen cross-linking defect
Ehler-Danlos Syndrome
collagen synthesis & fibril assembly

hyperflexibility & vascular weakness
Menkes
Cu def. / non fxn

--| cross linking w/ lysyl oxidase
Alport Syndrome
col. type IV def. (mutation)

inherited kidney failure
Goodpasture Syndrome
autoimmune

Ab attack type IV collagen

destroys basement membrane in lungs and kidneys

manage w/ corticosteroids / immunosuppressants
Osteogenesis Imperfecta
mut. type I collagen

*social issues -- can appear as abuse in infants presenting with broken bones
Collagen Type I
fibrilar (long, thin)

bone, skin, tendons, ligaments, internal organs
Collagen Type II
fibrilar (long, thin)

cartilage, invertebral disc, notochord, vitreous humor (eye)
Collagen Type III
fibrilar (long, thin)

skin, blood vessels, internal organs
Collagen Type IV
network forming, sheetlike

basal lamina / basement membrane
Basal Lamina
"basement membrane"

found underneath epithelial tissue, separates epithelium from connective tissue
Proteoglycan Structure
cushing, ↑ structural support {~hydration state}

*like a sponge for matrix
Chondrodysplasia
collagen def.

extremely flattened nose, oddly shaped legs, hip dysplasia (leg and knee problems), malformed fingers
Fibronectin Structure
between cell membrane & collagen

binds integrins

collagen binding site and cell binding site
Carcinoma
cancer of epithelial cells

must break contacts w/ laminins to metastasize
Integrins
everywhere!

fxn specific to cell types

can combine in any # of combinations
↑ variability
↑ specificity for specific integrin
Cadherins
regulate compaction

cells bind one another of same kind

"glue between epithelial cells"
CCN5
--| smooth muscle proliferation
MMPs
Matrix Metalloproteases

metal req. enzymes, imp. for angiogenesis

∴--| MMP, blocks tumor angiogenesis & growth
Diabetic Retinopathy
from unwanted angiogenesis
Prenatal Period
before birth
Postnatal period
after birth
Infancy
first year after birth
Newborn / Neonatal
first 4 weeks after birth
Childhood
13 mo. to puberty

primary deciduous teeth
active ossification
Puberty
♂ 13-16 y
♀ 12-15 y (onset of menarche)
Adolescence
11-19 y

earliest signs of puberty to attainment of physical, mental, and emotional maturity
Adulthood
begins at 18-21 y

full growth and maturity usually reached

ossification complete by 21-25 y
Menstrual Phase
days 1-5

shedding of lining

wall breaks off in pieces w/ 20-80 ml blood

*necrosis as a planned event
Proliferative phase
days 5-14

estrogenic phase; estrongen levels rise, stimulate re-growth of fxn layer

glands increase in number and length, spiral arteries elongate

coincides w/ follicles growth
Secretory phase
days 14-27

estrogen levels peak and fall
progesterone stays high

formation, fxn, growth of corpus luteum in ovary

epithelium secretes glycogen rich mucous fluid, endometrium thickens, spiral arteries coil, venous network forms lacunae

implantation on day 20
Ischemic phase
days 27-28 (if not fertilization)

estrogen / progesterone levels fall rapidly, fxn endometrium becomes ischemic

spiral arteries constrict, glandular secretion stops, fluid decreases, endometrium shrinks

necrosis of superficial tissues
Ovarian Cycle
GnRH made in neurosecretory cells in hypothalamus

secreted in rhythmic waves and carried by hypophyseal portal system to anterior pituitary
Ovarian Cycle (2)
ant. pit. releases FSH, stimulates 4-12 primordial follicles to develop
Primary Follicle Development
a) growth and differentiation of a primary oocyte
b) proliferation of follicle cells
c) formation of zona pellucda
d) development of the theca folliculi
Dominant Follicle
fastest growing follicle in stimulated group

becomes secondary follicle / primary oocyte and ultimately is ovulated as a secondary oocyte
theca folliculi
stroma cells adjacent to primary follices form a capsule

internal vascular/glandular layer: theca interna
capsule like outer layer: theca externa

promote angiogenesis
make follicular fluid, some estrogen, and androgens
Antrum
follicular fluid-filled region

when present, primary follicle becomes secondary follicle

surrounded by mass of cells called cumulus oophorus
LH surge
stimulates ovulation 12-24 later

elicited by rising estrogen levels reaching a threshold
stigma
visible cystic swelling on ovarian suface -- marks rapid growth of follicle
Graafian follicle
mature
Corona Radiata
one or more layers of follicle cells suoorounding ovulated secondary oocyte
Corpus Luteum
follicle walls and theca folliculi collapse to form glandular corpus luteum

secretes progesterone and some estrogen

degeneration prevented by hCG
Progesterone
causes endometrial glands to secrete glycogen-rich mucous fluid to prepare endometrium for implantation
Corpus Albicans
a small patch of white scar tissue left over from CL if no fertilization occurs
Oocyte transport
fimbriae and infundibulum at end of fallopian tube sweep secondary oocyte into tube

peristalsis & ciliar mvmt bring oocyte to ampulla
Anovulation
failure to ovulate

freq. caused by inadequate levels of gonadotropins

can treat w/ clomiphene citrate
Sperm Production
occurs throughout lifetime of ♂
Sperm Counts
normal 100 million / ml, >40% motile

infertile <10 million/ml, <20% motile
Capacitation
glycoprotein coat and seminal proteins are removed from acrosomal surface of sperm

activates sperm for acrosomal rxn
ACE

Angiotensin Converting Enzyme
in acrosome, req. to induce acrosomal rxn
♂ Contraception
Vasectomy

reversible 50% of the time
Sperm Mvmt in ♀
swim 2-3 mm / min

muscular contractions in ♀ reproductive tract stimulated by prostaglandins (*most of the mvmt)
Fertilization
occurs in ampulla of fallopian tube, take 24 hours

begins w/ penetration of zona pellucida
ZP3
primary CHO mol. rec. on oocyte by sperm

binding initiates acrosomal rxn
Hyaluronidase
from the acrosome disperses follicular cells surrounding oocyte by eating ECM (degrades hyaluronan)
Zona Reaction
sperm contacts oocyte membrane, cortical granules exocytose contents, cross link zona proteins

*slow block to polyspermy
Membrane Fusion / Fertilization
triggers completion of Meiosis II, release of second polar body

sperm brings centriole for mitotic spindle

pronuclei formed, membranes break down, chromosomes condense, begin metaphase
Zygote
unicellular embryo, 46 chromosomes (2n)

G prot, Ca++, IP3, prot kinases trigger activation of new zygotic genome
Parthenogenesis
embryonic development without sperm

artificial induction of oocyte cleavage possible in some animals, not humans
Polyspermy
several sperm fertilize oocyte

severe intrauterine growth retardation and developmental anomalies

not compatible w/ life
Selective Reduction of Multiple Pregnancies
presents ethical issues in IVF

mult. embryos ↑ mother's risk of complications
Ethical Issues w/ Infertility Treatments
Limited access due to high costs

unknown long term medical risks (ex. ICSI)

Are infertility treatments a health right or a privilege?
Somatic cell
cell of the body other than egg or sperm
SCNT

(Somatic Cell Nuclear Transfer)
the transfer of a cell nucleus from a somatic cell into an egg from which the nulceus has been removed
Stem Cells
cells that have the ability to divide for indefinite periods in culture and to give rise to specialized cells

*self-renewing
Totipotent
unlimited capacity to specialize into any and all cell types or tissues

"omnipotent"
Pluripotent
capable of giving rise to most cells and tissues of an organism
Multipotent
capable of giving rise to several/many cell types
Progenitor cells
cells that are committed to differentiate

NOT self-renewing, (not stem cells)
Clone
an organism, colony, or group of organisms derived from a single organism or cell by asexual reproduction

*all have identical genetic make-ups
Reproductive Cloning
cloning to produce a pregnancy resulting in the birth of a baby
Therapeutic Cloning
cloning to produce embryonic stem cells for treatment of disease
Properties of a good stem cell
survive in liquid nitrogen freezing for years
survive and proliferate indefinitely in cell culture
maintain stable and normal DNA and chromosomes
differentiate predictably into many types of cells
ES

(Embryonic Stem Cells)
+ low cost, unlimited #, pathogen free, non-carcinogenic, reduced immune rejection
++ more plastic

- ethical issues!
Adult Stem Cells
+found in most tissues, isolated from live of cadaver tissues
++ few ethical concerns

- less plastic
Umbilical Cord Blood Stem Cells
+ fewer ethical concerns
+possibility of a matched set of stem cells for autotransplantation later in life
Transgenic Animals
substitute genetically modified cell into 8 cell embryo

modified trait will show up in some cells/tissues/organs

genetic crosses of those chimeras having alteration in germ-line will yield animals w/ genes for new trait in all cells

-also, inject modified DNA into male pronucleus of fertilized egg
tPA
tissue plasminogen activator

*clot buster*

can tie to mammary gland specific activator in goat, ∴ tPA rich in goat's milk, ... milk it and purify enzyme
Rubella (German Measles)
causes birth defects

used to map progression of development (stage of development at time of infection determines specific defects)
Thalidomide
used in leprosy treatments

powerful teratogen, many birth defects

also used to map developmental progression
Burkitt's Lymphoma
c-myc translocation

reveals mol. and mech. for pro- & anti-apoptotic events

Bcl-2 misregulation, anti-apoptotic signals, --> massive outgrowths
Syndactyly
lack of apoptosis

webbed fingers / toes

no apoptosis to differentiate structures
Polydactyly
wrong timing or wrong amount of apoptosis

make too many fingers or toes