Developmental Block 1

Front 1

Max Oogonia

Back 1

5th Prenatal Month = 7 Mill

Front 2

First Arrest of Oogenesis

Back 2

Primary oocyte arrested in prophase 1 until puberty due to follicular cells releasing "oocyte maturation inhibitor"

Front 3

In oogenesis, when does meiosis 1 complete?

Back 3

Just prior to ovulation!

Front 4

Second Arrest of Oogenesis

Back 4

Metephase 2

Front 5

What marks the beginning of spermatogenesis?

Back 5

When spermatagonia differentiate to Type A Spermatagonia at puberty.

Front 6

Microdeletions

Back 6

Losing a few continuous genes

Dependent on paternal or maternal genetic material = Genomic Imprinting

Front 7

Chromosomal Abnormality Rate

Back 7

1/125 Births

Front 8

Gene Mutation Result in:

Back 8

7-8% of all malformations

Front 9

Achondroplasia

Back 9

Dwarfism

Single G-A transition

Front 10

Where do sperm fertilize ovum?

Back 10

Ampulla (Uterine Tube)

Front 11

Average Ejaculate

Back 11

3.5 mL, 10% Sperm (200 Mill Sperm/mL)

Front 12

Ejaculate Composition

Back 12

10% Sperm

The rest is fluid:
60% Seminal
30% Prostate
10% Bulbourethral

Front 13

Sterile

Back 13

Male with fewer than 10 Mill sperm/ mL of semen.

50% of sperm should be motile after 2 hours

Front 14

Capacitation

Back 14

Lasts 7 hours

Removal of glycoprotein coat and seminal proteins from surface of acrosomal membrane

Occurs in fallopian tube or uterus (where it is stimulated)

Result = sperm more active, can pass corona radiata, acquire ability to undergo acromsome reaction

Front 15

6 Stages of Fertilization:

Back 15

1) Penetration of corona radiata
2) Penetration of zona pellucida
3) Fusion of 2 plasma membranes
4) Completion of oocyte's 2nd meiotic division/ formation of female pronucleus
5) Formation of male pronucleus
6) Formation of zygote

Front 16

Penetration of corona radiata (stage 1 of fertilization)

Back 16

Sperm contact = molecular changes = multiple point fusions of acrosomal cap = release of enzymes (hyaluronidase)

Enzymes from tubal mucosa/ sperm tail also help

Front 17

Penetration of zona pellucida (stage 2 of fertilization)

Back 17

Most significant stage

Binding of sperm causes acrosome reaction = exocytosis of acromsomal enzymes (esterases, acrosin, neuraminidase) = lyse pathway for sperm

Penetration of zona pelucida causes cortical reaction = release of cortical granules

Granules alter zona receptor proteins which causes zona reaction = zone pelliucida become impermeable

Front 18

Formation of the male pronucleus (stage 5 of fertilization)

Back 18

Forms Ootid = Oocyte, containing 2 haploid pronuclei

Front 19

Formation of zygote (stage 6 of fertilization)

Back 19

Male and female pronuclei fuse, forming single diploid aggregate = zygote

Front 20

Cleavage of Zygote

Back 20

Days 1-5

Front 21

Day 2 Post Fertilization

Back 21

Cleavage continues

2.5 days = 8 cells

Front 22

Day 3 Post Fertilization

Back 22

12-32 blastomeres = morula

Enters uterus

Front 23

Day 4 Post Fertilization

Back 23

Blastocyst cavity forms

As fluid in cavity increases, blastomeres separate into 2 parts:

thin outer cell layer = trophoblast
inner cell mass = embryoblast

Front 24

Day 5 Post Fertilization

Back 24

Zona pellucida degenerates

Blastocyst "hatches" and size increases rapidly

Front 25

Day 6 Post Fertilization

Back 25

Blastocyst attaches to endometrial epithelium

Attachment triggers proliferation of trophoblast into: Cytotrophoblast (inner layer)
Syncytiotrophoblast (outer layer or mass)

Decidual Rxn Begins

Front 26

Day 7 Post Fertilization

Back 26

Syncytiotrophoblast invades endothelium of uterus, superficially implanting it there

Embryoblast begins to differentiate into "bilaminar" embryo:
hypoblast and epiblast

Front 27

EPF

Back 27

Early Pregnancy Factor

Shortly after fertilization, zygote stimulates ovary to produce EPF

Immunosuppressant

Appears 24-48 hrs after fertilization

Front 28

hCG

Back 28

Human chorionic gonadotropin

Glycoprotein hormone produced by syncytiotrophoblast

Levels peak at about 8-10 weeks of gestation

Detected in blood by day 8 and urine by day 10

Front 29

Embryoblast cell features:

Back 29

Pluripotentiality = can develop into any cell of embryo, but NOT into trophoblast cells

Front 30

Blastomere/Zygote cell features:

Back 30

Totipotentiality = can develop into any cell of trophoblast or embryoblast

Front 31

Day 8 Post Fertilization

Back 31

Amniotic Cavity develops within Epiblast (first cavity)

Front 32

Day 9 Post Fertilization

Back 32

Point of implantation marked by coagulation plug

Amnioblasts line the amniotic cavity and will form the amnion or amniotic membrane

Cells from hypoblast migrate and form exocoelomic (Heuser's) membrane

Blastocyst cavity is now referred to as the exocoelomic cavity (2nd cavity)

Front 33

Day 10 Post Fertilization

Back 33

Exocoelomic membrane develops, exocoelomic cavity becomes umbilical vesicle or yolk sac

Extraembryonic mesoderm develops between exocoelomic membrane and cytotrophoblast

Lacunae begin to appear in the syncytiotrophoblast - embryotroph passes through these to nourish embryo

Front 34

Day 11 and 12 Post Fertilization

Back 34

Blastocyst completely embedded in endometrium

Syncytiotrophoblast penetrate deeper, eroding endothelial cells of maternal capillaries, causing them to become continuous with lacunae = early uteroplacental circulation

Several cavities appear in extraembryonic mesoderm and become confluent, forming extraembryonic coelom (chorionic cavity) (3rd cavity)

Front 35

Day 13 Post Fertilization

Back 35

Extraembryonic coelom (chorionic cavity) expands

Primar yolk sac/umbilical cord pinches off, forming secondary yolk sac

Extraembryonic mesoderm differentiates into:
Extraembryonic somatic mesoderm (lines trophoblast and covers amnion)
Extraembryonic splanchnic mesoderm (surrounds yolk sac)

Primary Chorionic Villi Develop

Front 36

Day 14 Post Fertilization

Back 36

Localized circular area of hypoblast becomes columnar (future site of mouth) = Prechordal Plate = Important organizer of head region

Front 37

Formation of Notochord

Back 37

Third Week

Group of cells migrates from primitive pit = Notochordal process

Migration forms notochordal canal

Day 19-20, notochordal process fuses with underlying embryonic endoderm causing floor of notochordal process/ underlying endoderm to break down

Remaining flattened structure is called notochordal plate

Notochordal plate folds ventrally to become the tubular notochord

Front 38

Ectoderm Derivatives

Back 38

1) Surface Ectoderm

2) Neuroectoderm

Front 39

Surface Ectoderm (7)

Back 39

AM SHEEP

Adrenal Medulla
Mammary Glands

Subcutaneous Glands
Hair
Epidermis
Enamel
Pharyngeal Arch Cartilages

Front 40

Neuroectoderm (2)

Back 40

Neural Crest
Neural Tube

Front 41

Paraxial Mesoderm

Back 41

Organizes into paired segments = somitomeres

Added cranio --> caudal at 3-4/day

Somitomere Pairs 1-7 = do NOT form somites, give rise to musculature of face, jaw, throat

Somitomeres 8,9,10 --> 1st, 2nd, 3rd pairs of Somites --> bones of face/extraocular muscles/muscles of tongue

At end of 5th week, 42-44 pairs of somites --> some degenerate in caudal end --> final somite count = 37-38

Front 42

Purpose of Somites

Back 42

Establish segmental organization of body

Give rise to most of the axial skeleton, voluntary muscles, part of dermis of skin

Front 43

Intermediate Mesoderm

Back 43

Temporarily connects paraxial mesoderm with lateral mesoderm

Differentiates into urinary system and part of the genital system

Front 44

Lateral Mesoderm

Back 44

Splits into two layers:

1) Splanchnic or Visceral Mesoderm - Coverings of Visceral Organs

2) Somatic (Dorsal) or Parietal Mesoderm - Body wall, parts of limbs, most of dermis

Front 45

Splanchnopleure

Back 45

Splanchnic (Visceral) Mesoderm + Underlying endoderm

Front 46

Somatopleure

Back 46

Somatic (Parietal) Mesoderm + Overlying ectoderm

Front 47

Intraembryonic Coelom

Back 47

Horseshoe shaped space between splanchnic and somatic mesoderm

Posterior opening in space becomes continuous with extraembryonic coelom

After folding in week 4, space becomes thoracic and abdominal cavities

Front 48

Endoderm

Back 48

1) Parenchyma of glands

2) Epithelial lining of :
-Respiratory System
-Urogenital System
-Various Pharyngeal Pouches

Front 49

Fate Map of Epiblast Cells: Cranial Most Portion of Primitive Node --> Caudal Most Portion of Primitive Streak

Back 49

Notocord --> Paraxial Meso --> Int Meso --> Lateral Plate Meso ---> Extraembryonic Meso

Front 50

Neurulation

Back 50

Notochord functions as an inducer

Overlying ectoderm forms elongated plate of thickened epithelial cells, the Neural Plate

Neural plate invaginates to form Neural Groove, flanked by 2 Neural Folds

At end of 3rd week, folds fuse to form Neural Tube (proceeds cranially to caudally)

Anterior and posterior neuropores close at approximately day 26 and 28, respectively.

Front 51

Neuroectoderm

Back 51

Ectoderm of neural plate

Gives rise to CNS (brain and spinal cord)

Front 52

Neural Crest Formation

Back 52

Formed by neuroectodermal cells lying along neural folds detaching

Front 53

Neural Crest Cells are precursors of the following: (6)

Back 53

PPP GAS

PNS
Pigment Cells
Pharyngeal Cartilages

Ganglia of ANS
Adrenal Medulla
Spinal Ganglia

Front 54

Induction of Neural Precursor Cells

Back 54

BMP4 induces epidermal specific genes, and suppresses neural genes

Noggin/Chordin/Follistation prevent BMP4 binding to ectoderm = Neural tissue formation

Front 55

Shh and Dorsoventral Axis Formation

Back 55

Shh binds to surface receptor, activates TF cubitus intruptus (Ci or Gli in mammals)

Cholesterol activates Shh and Patched (which binds Shh)

Gradient of BMP4 causes proliferating neural cells in dorsal side to become sensory

Front 56

Teratogens

Back 56

Environmental agents that disrupt normal development

Ex. RA, Thalidomide

Front 57

3 Areas with NO Mesoderm between Ectoderm/Endoderm?

Back 57

1) Oropharyngeal Membrane (future mouth)
2) Cloacal Membrane (future anus)
3) Notochord

Front 58

Crani-Caudal Axes Formation:

Back 58

Signaled by AVE (anterior visceral endoderm) which secretes:

1) TFs (OTX2, LIM1, HESX1)
2) Cerberus

Primitive streak is initiated/maintained by Nodal

Front 59

Dorsal-Ventral Axes Formation:

Back 59

BMP4 secreted throughout bilaminar disc

In presence of FGF, mesoderm is ventralized to contribute to intermediate and lateral plate mesodermal structures

Genes expressed by primitive node antagonize BMP4 = dorsalization of mesoderm (thus, node is called "organizer")

Cranial meso dorsalized into notochord, somites and somitomeres through antagonism of BMP4 through chordin, noggin, and follistation (activated by TF Goosecoid)

Brachyury regulates formation of dorsal mesoderm in middle and caudal portions

Front 60

Left-Right Axes Formation

Back 60

FGF8 (secreted by cells in primitive node/streak) induce expression of Nodal on LEFT side (gradient produced by cilia bearing cells)/ maintains Lefty-2 in lateral mesoderm

FGF8 + Lefty-2 = upregulation of PITX2 (establishes left side)

Lefty-1 prevents left signals from crossing over

Brachury essential for the expression of all three of these left side genes

TF Snail is restricted to right side, but not well understood

Front 61

Breakdown of Buccopharyngeal Membrane and Cloacal Membrane:

Back 61

1) Buccoprayngeal Membrane:
-Ruptures 4th Week
-Forms connection between amniotic cavity and primitive gut (foregut)


2) Cloacal Membrane:
-Ruptures 7th Week
-Creates anal opening of hindgut

Front 62

Fetal Membranes (4)

Back 62

Chorion
Amnion
Umbilical Vesicle (yolk sac)
Allantois

Front 63

Blastocyst Effects on Uterus

Back 63

hCG secretion- causes ovary top continue producing progesterone which maintains endometrium

Prevents production of prostaglandins (which cause decrease in progesterone production)

Prevents production of HLA antigens

Front 64

Decidual Reaction

Back 64

Endometrial stroma cells surrounding the implantation site become loaded with glycogen and lipids

Decidual cells degenerate, undergoing apoptosis, and syncytiotrophoblasts engulf them for nutrients

Also provides protection immunologically

Front 65

Decidua

Back 65

Functional layer of endometrium in a pregnant woman

Three regions:
1) Decidua basalis
2) Decidua capsularis
3) Decidua parietalis

Front 66

Chorionic Villi

Back 66

Development begins at approx 13 days with formation of Primary Chorionic Villi

Induced by extraembryonic mesoderm

Outgrowths of cytotrophoblasts which invade syncytiotrophoblast

Front 67

Secondary Chorionic Villi

Back 67

Develop at about 15 or 16 days

Extramembryonic mesoderm penetrates core of primary villi

Front 68

Tertiary Chorionic Villi

Back 68

Develop at about 20 to 21 days

Villous mesoderm gives rise to blood vessels that will soon fuse to form an arteriocapillary-venous system, which will soon become connected to the embryonic heart

Front 69

Placental Septa

Back 69

Wedge shaped areas of decidual tissue formed by invasion of decidulaized endometrium by chorionic villi

These septa divide fetal part of placenta into 10-38 cotyledons

Front 70

Smooth Chorion (laeve)

Back 70

Some villi are compressed and degenerate as chorionic sac grows and embryo begins to bulge into uterine cavity

AKA "Abembryonic" side of chorion

Front 71

Villous Chorion (chorion frondosum)

Back 71

Chorionic villi of "embryonic" side of chorion increase in number and branch profusely as other areas of villi degenerate

Front 72

Attachment of Villous Chorion with maternal part of placenta (decidua basalis):

Back 72

Extension of cytotrophoblast cells through syncytiotrophoblast

Endometrial vessels pass through and open into the intervillous space

Front 73

Amniochorionic Membrane

Back 73

Amniotic sac enlarges faster than chorionic sac, so they eventually fuse

Then fuses with deciduas capsularis, and after its disappearance, fuses with deciduas parietalis

Rupture of this membrane = "water breaks"

Front 74

Fetal Placental Circulation

Back 74

Deoxy blood leaves fetus via 2 umbilical ARTERIES to the placenta

Umbilical arteries divide into chorionic arteries

Chorionic arteries branch in chorionic plate, then enter villi

Oxy blood in fetal capillaries pass into veins, which converge

Oxy Blood returns to fetus in 1 umbilical VEIN

Front 75

Maternal Placental Circulation

Back 75

Maternal blood enters intervillous space through 80-100 spiral endometrial arteries in decidua basalis and due to high pressure, spurts toward chorionic plate and through gaps in cytotrophoblastic shell

Blood perfuses the villi, and eventually exits through endometrial veins

Front 76

Where does the main exchange between fetal and maternal circulation take place?

Back 76

Branch chorionic villi

Front 77

4 Placental Membrane Layers until week 20:

Back 77

1) Endothelial lining of fetal blood vessel
2) Connective tissue in the villus core
3) Cytotrophoblastic Layer (after 20 weeks, disappear and become very thin in some areas)
4) Syncytiotrophoblast

Front 78

Fetal Erythroblastosis

Back 78

Rh positive fetus + Rh negative mother = antibodies attack!

Front 79

Additional Placental Functions:

Back 79

1) Synthesizes glycogen, cholesterol, and fatty acids

2) Exchange between maternal/fetal blood

3) Transfer of maternal antibodies

Front 80

Fate of Yolk Sac

Back 80

Dorsal portion incorporated as primitive gut

Site of primordial germ cells during 3rd week

Forms allantois

No longer visible after 20 weeks

Front 81

Allantois

Back 81

Outpouching of wall of yolk sac that extends into connection stalk

Functions:
1) Blood formation during weeks 3-5
2) Allantoic blood vessels become umbilical vein and arteries
3) Intraembryonic portion forms urachus (becomes median umbilical ligament after birth)

Front 82

Amniotic Fluid

Back 82

Initially secreted by amniotic cells, but most is derived from maternal blood

99% H2O

Fx:
1)Permits symmetrical external growth
2)Permits normal fetal lung development
3) Prevents amnion from adhering to embryo
4)Cushions embryo
5) Enables fetus to move
6) Maintains homeostasis
7) Barrier to infection

Front 83

Oligohydramnios

Back 83

Low V of amniotic fluid

Can be sign of renal agenesis

Front 84

Polyhydramnious

Back 84

Fetus swallows abnormal amount of amniotic fluid

May be associated with esophageal atresia

Front 85

Placenta Inspection:

Back 85

Size: D = 22 cm, thickness = 2.5 cm

Weight = 470 g

Shape - discoid

Completeness

Umbilical vesicles

Presence of accessory lobes, hemorrhage, tumors, or nodules

Front 86

Umbilical Cord Inspection:

Back 86

Length = 55-60 cm

Diameter = 2-2.5 cm

Vessels = 2 arteries, 1 vein

Knots

Thromboses

Whartons Jelly

Front 87

Timeline of Vasculogenesis and Angiogenesis

Back 87

Vasculogenesis: Limited period of time early in embryonic development

Angiogenesis: Throughout development and in adulthood

Front 88

Factors Important for Angiogenesis:

Back 88

FGF

VegF

Front 89

Leading non-infectous cause of death in children?

Back 89

Congenital heart disease

Front 90

Master Key Gene for Heart Development

Back 90

NKX2.5

Expression through BMP2/4 and inhibition of WNT

Front 91

Earliest heartbeats detected when?

Back 91

Early week 4

Front 92

Structures blood flows through in primitive heart:

Back 92

Students Are Very Bright Taking Adderall

Sinus Venosus --> Atrium --> Ventricle --> Bulbus Cordis --> Truncus Arteriosus --> Aortic Sac and Arches

Front 93

First Visible Asymmetry of Heart

Back 93

Growth of heart tube produces looping to right

Positions heart to left side

Front 94

Timing of Pleuroperitoneal Folds Uniting with the Dorsal Mesentery of the Esophagus to FORM THE POSTERO-LATERAL MUSCULATURE OF THE DIAPHRAGM

Back 94

Opening on Right Closes FIRST!

Front 95

What forms the Crura of the diaphragm?

Back 95

Mesentery of Esophagus

Front 96

What forms the Margins of the Diaphragm?

Back 96

Muscular Ingrowth from Body Wall

Front 97

What cell layer(s) is/are involved in forming/partitioning the trachea?

Back 97

Forming: Mostly Endoderm
Neural Crest Cells give rise to Laryngeal cartilages and muscles

Partioning: Mesoderm (tracheoesophageal folds --> tracheoesophageal septum)

Front 98

4 (5) Periods of Development of Lungs

Back 98

Poor Children Try Stealing Anything (PCTSA)

1) Pseudoglandular (weeks 6-16) - Die

2) Canalicular (16-24 or 26) - Maybe

3) Terminal Sac (Week 24 or 26 - Birth) - Maybe

3') Surfactant (Weeks 26-28) - Usually Live

4) Alveolar (32 Weeks - 8 Years) - Live --> Period of Viability!

Front 99

Respiratory Distress Syndrome (RDS)

Back 99

AKA Hyaline Membrane Disease

Deficiency of absence of surfactant

Treatment: Administration of corticosteroids (e.g. betamethasome) prior to birth/postnatal administration of artificial surfactant/high f ventilation.

Front 100

Gene Expression and Respiratory System

Back 100

Mesoderm surrounding primitive tubular airways controls branching of endoderm

Branching (Bronchial Buds): FGF-10 produced by mesoderm stimulates endoderm to branch

NO Branching (Trachea):
Shh produces protein which Inhibits FGF-10

Front 101

Where does hematogenesis first occur?

Back 101

Liver at about Week 5

Front 102

Fate of Vitelline Veins (Yolk Sac)

Back 102

R Vitelline:

Portal System of Veins
Hepatic Sinusoids and Hepatic Veins
Portion of IVC

Front 103

Fate of Umbilical Veins (Placenta)

Back 103

Distal L Umbilical:

Empties into Liver

Can bypass Liver through Ductus Venosus, which empties into IVC

Left Umbilical Vein CLOSES AFTER BIRTH - in adult it is seen as ligamentum teres or round ligament of liver

Front 104

Fate of Cardinal Veins (Embryo)

Back 104

Caudal Left Anterior Cardinal DEGENERATES as Left Brachiocephalic Vein develops

Proximal portion of Right Anterior Cardinal + Right Common Cardinal form SVC

Posterior Cardinal Veins are Replaced and Supplemented first by Subcardinal, and then by Supracardinal Veins.

Front 105

Components/Origin of IVC (4)

Back 105

I Ran So Hard

Infrarenal- R Supracardinal
Renal - Sub and Supra Cardinal Anastomosis
Suprarenal- R Subcardinal
Hepatic Segment- R Vitelline

Front 106

Fate of Arch 1 of Aortic Sac

Back 106

Most Degenerates

Maxillary Artery

Front 107

Fate of Arch 2 of Aortic Sac

Back 107

Most Degenerates

Stapedial and Hyoid Artery

Front 108

Fate of Arch 3 of Aortic Sac

Back 108

Common Carotid Arteries

First Part of Internal Carotid Arteries

Front 109

Fate of Arch 4 of Aortic Sac

Back 109

R - Proximal Right Subclavian

L - Arch of Aorta

Front 110

Fate of Arch 5 of Aortic Sac

Back 110

Rudimentary

Front 111

Fate of Arch 6 of Aortic Sac

Back 111

R - Proximal Right Pulmonary Artery

L - Proximal Left Pulmonary Artery + Ductus Arteriosus

Front 112

Formation of Right Lymphatic Duct:

Back 112

Cranial Portion of Right Duct

Front 113

Formation of Thoracic Duct:

Back 113

Caudal Portion of Right Duct + Anastomosis + Cranial Portion of Left Duct

Front 114

Gene NKX2.5

Back 114

Heart Specifying Gene (Tinman Gene in Drosophila)

Mutations produce ASDs (secundum type) and Tetralogy of Fallot