Mcp Lect 24-28: Embryology

Front 1

Differentiation

Back 1

Differentiation - process by which cells take on their separate identity - occurs on the level of cells

Front 2

Morphogenesis

Back 2

Morphogenesis - process that gives rise to the shapes and forms of tissues and organs - occurs on the level of tissues

Front 3

Gastrulation

Back 3

Formation of 3 germ layers
1. Ectoderm (AKA the epiblast)
2. mesoderm
3. Endoderm (AKA the hypoblast initially, followed by the definitive endoderm)


(Note: Used to think hypoblast became primitive gut. Primitive endoderm of hypblast is replaced by true gut endoderm. Learned this via transgenic mice. )

Front 4

Fertilization

Back 4

A sequence of events beginning with contact between sperm and the secondary oocyte and ending with fusion of maternal and paternal nuclei resulting in intermingling of their chromosomes.

A. Passage of sperm through the corona radiata
B. Penetration of the zona pellucida
C. Fusion of the oocyte and sperm plasma membranes
D.The oocyte completes the second meiotic division
E. Formation of the male pronucleus

Front 5

Super important steps of development:

Back 5

1. Fertilization
2. Compaction
3. Blastocyst formation
4. Implantation
5. Gastrulation

Front 6

Capacitation

Back 6

-occurs in oviduct
-secretions of oviduct tube alter plasma membrane of sperm
-necessary for sperm to undergo acrosomal reaciton
-allow sperm tail to stop moving wildly so they can move with ACTIVE FORWARD MOTILITY

Front 7

What enzymes does the sperm release when it meets with the corona radiata?

Back 7

ACROSOME REACTION:
1. hyaluronidase
2. acrosin
**eats between radiata cells

Front 8

What proteins are responsible for sperm + egg?

Back 8

Sperm has fertilin, binds to integrins on the egg

Front 9

Block to polyspermy

Back 9

After hydrolytic enzymes are released from the acrosome of the sperm and they form a channel through the zona pellucida through which the sperm makes contact with the plasma membrane of the oocyte, a ZONA REATION occurs in which enzymes located in cortical granules on the innermost cytoplasmic side of the oocyte are released into the perivitelline space causing the zona to change chemically resulting in it becoming impermeable to other sperm. This block to polyspermy ensures a diploid phenotype of the resulting zygote.

**cortical release triggered by waves of intracellular calcium

Front 10

What part of the sperm enters the egg?

Back 10

The head and tail of the sperm enter; plasma membrane left behind

Front 11

zygote

Back 11

haploid male and female pronuclei come in close contact near each other and lose their nuclear membranes allowing the maternal and paternal chromosomes to intermingle

46 chromosomes
2n

Front 12

ICSI

Back 12

Intra Cytoplasmic Sperm Injection

-way to circumvent male infertility due to defective sperm
-Bypasses:
1. passage of sperm through the corona radiata
2. penetration of the zona pelucida
3. fusion of the oocyte and sperm plasma membranes
4. exclusion of sperm membrane from cytoplasm

Can solve some short-term problems with regard to male infertility such as low sperm count, lack of sufficient sperm mobility, and/or lack of enzymatic reactions needed for sperm entry
*but think about the offspring's sperm.. fail.

Front 13

Blastomere

Back 13

2cell -- 8 cell stage
retained within the zona pellucida, so progressively smaller blastomeres are formed

Front 14

Compaction

Back 14

Blastomeres change their shape and undergo compaction (flattening on each other, make cell adhesion junctions) into a ball of 12 or more cells called the morula

Front 15

Where does zygote cleavage to form the morula generally occur?

Back 15

within the oviduct over about 3-4 days

Front 16

Blastocyst

Back 16

INNER CELL MASS + TROPOBLAST

following compaction of the morula, greater cell-to-cell interactions results in differentiation of a blastocyst.
trophoblast cells -- give rise to part of the placenta
inncer cell mass (stem cells) -- give rise to the embryo

Front 17

When does the embryo hatch?

Back 17

morula stage ~day 3
before compaction

Front 18

At what stage does the embryo implant?

Back 18

At the blastocyst stage

typically occurs in the endometrium, but can occur other places and are called ectopic pregancies

Front 19

What cells are totipotent? What cells are pluirpotent? When does this switch occur?

Back 19

Totipotent:
zygote
blastomere
morula

Pluripotent:
inner cell mass in the BLASTOCYST
(the tropoblast is differentiated)

*onset of differentiation occurs at the 12 cell stage because its at this point that (geometrically) you can have a cell that's INSIDE and cells OUTSIDE -- aka cells have different environments
***this is driving force for differentiation

Front 20

What cells secrete estrogen during the luteal phase? Progesterone?

Back 20

Theca lutein cells of the corpus luteum produce estrogen.

Progesterone is produced by the granulosa lutein cells of the corpus luteum.
**high levels of progesterone inhibit the positive feedback of estrogen and inhibits follicular development

Front 21

What happens if implantation occurs? If it doesnt?

Back 21

If implantation does not occur 12 days after ovulation the corpus luteum finally degerates ceasing production of progesterone and estrogen. The inhibitory action of estrogen and progesterone is removed allowing LH and FSH to increase and a new cohort of follicles to grow. The drop in both estrogen and progesterone brings on menses.

If implantation occurs, the stromal cells of the endometrium enlarge in response to increased progesterone. The corpus luteum is rescued by hCG from the placenta that replaces the LH,

Front 22

Tissues of the uterus

Back 22

Perimetrium – outer layer
myometriumn – muscle, contracting
endometrium – inner, where embryo emplants

*During secretory phase Three layers of endometrium are distinguishable.
i. Compact Layer
ii. Spongy Layer
iii. Basal Layer
2. Basal layer of endometrium has its own blood supply and is not sloughed off during menstration, but the compact and spongy layers are

Front 23

RU486

Back 23

Ru486 = drug binds to progesterone receptors..
Competitive receptor ANTAGONIST. Uterus behaves as if there is NO progesterone there.
Fails to activate receptor.
This causes MENSES.
Doesn’t let progesterone bind to receptors and activate it

2mg daily dose – general prevention 10 mg single dose again – day after pill

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Back 24

Front 25

Back 25

Front 26

Back 26

Front 27

Back 27

**trophectoderm cells bind to endometrial epitheliumsend out stuff liike mmp9 = metalic protease eats away at those cells gets into endometrium

Front 28

What % of twins are dizygotic?

Back 28

2/3

Dizygotic twins originate from two zygotes
Dizygotic twins result from the fertilization of two ova by different sperm
They can be the same sex or different
Generally they have two separate placentas, although the placentas may become fused
Dizygotic twins are no more alike than brothers or sisters born at different times
Dizygotic twinning shows a hereditary tendency with the risk of recurrence about 3x that of the general public

Front 29

What % of twins are monozygotic?

Back 29

1/3

Monozygotic twins result from fertilization of the same ova. Monozygotic twinning usually begins in the BLASTOCYST stage by the division of the inner cell mass into two embryonic primordia. Subsequently, two embryos, each in its own amniotic sac, develop and have a common placenta. Monozygotic twins are of the same sex, genetically identical, and share a very similar appearance. Slight physical differences result from environmental influences.

Front 30

Conjoined twins

Back 30

Conjoined twins result from incomplete division of the embryonic disc of monozygotic twins. An example of conjoined twins are Siamese twins. conjoined twins can be fused by skin only or they can share fused organs (liver, skull, etc.)

Front 31

Clones

Back 31

The manipulation of donor somatic cells with an identical genome to produce identical embryos which when implanted in a host can produce embryos with a genetic composition identical to each other and to the donor.
Clones may be larger than the donor (lack of genomic imprinting?) and telomeres are shortened

Front 32

How to make a clone!

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a. remove the nucelus from a somatic cell donor
b. implant the nucleus into an enucleated host ooctye or one zygote derived from the surrogate mother to be
c. treat the new nucleus/cytoplasm with certain growth factors and apply small electrical charge
d. implant the treated cell into the uterus of the surrogate mother

Front 33

Differences between clones and monozygotic twins

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A. temporal difference in date of births
B. clones exhibit shortened telomeres
C. clones are less viable
D. clones may be larger due to lack of genomic imprinting
E. Clones exhibit features of premature aging

Front 34

Inhibin

Back 34

Mechanism of function unclear
-made in granulosa cells
-feeds back on the pituitary to inhibit FSH
-also seems to help speed up the regression of the corpus luteum when pregnancy does not take place

Front 35

Decapacitation protein

Back 35

aka phosphatidylethanolamine-binding protein 1 (PEBP 1)
-a receptor in the sperm membrane
-plays a fundamental role in capacitation by causing alteration in the sperm plasma membrane in both head and flagellum, with functional consequences for membrane-associated proteins
-functions prior to capacitation by organizing phospholipids and proteins within the membrane so the sperm can undergo capacitation
-it must be removed for capacitation to proceed normally

Front 36

Premordial v. primary follicle?

Back 36

Primordial follicle occurs before birth and soon after birth and are surrounded by a single layer of flattened follicle cells. The oocyte is in prophase 1.

The primary follicle is seen after birth and is identifiable by the cubodial single layer of follicle cells. The oocyte is sitll at prophase 1.

Front 37

How do high levels of estrogen convert from negative to positive feedback on LSH secretion during hormonal control of the uterine cycle? What is the mechanism?

Back 37

It is all in how many receptors in the pitutary are occupied by estrogen. If a few are occupied then LH (not LSH) secretion is suppressed. If high numbers of estrogen receptors are occupied within the pitutary, these cells behave differently by secreting LH. It's not receptor popultaion shifting, it's the number of receptors occupied.

Front 38

What hormone(s) causes body temp to rise during ovulation?

Back 38

Mostly estrogen and to a lesser extent progesterone

Front 39

Function of the corpus luteum?

Back 39

Secrete progesterone until the middle of the first trimester, after which the chorion secretes necessary progesterone

Front 40

Gastrulation

Back 40

Process by which the bilaminar germ disc (epiblast and hypoblast) is transformed into a trilaminar structure (ectoderm, mesoderm, and endoderm)

begins early in week 3

marked by extensive cell migration

Front 41

Embryonic development consists of two processes:

Back 41

1. Morphogenesis (tissues take on shape)
2. Differentiation (cells take on identity)

Front 42

Extraembryonic mesoderm

Back 42

-most, but not all, of the extraembryonic mesoderm is formed prior to gastrulation from the epiblast cells in the peripheral and caudal regions of the disc
-forms the amnion, chorion and yolk sac
-the cells at the junction between embryonic and extraembryonic mesoderm are pluripotent and, depending on the environemtn, will differentiate into extra or embryonic mesoderm

Front 43

On day 16 of development, the germ disc consists of two layers (name the two layers). It contains the following structures (name the structures).

Back 43

Germ disc consists of two layers: epiblast and hypoblast

Structures:
1. Buccopharyngeal membrane
-region where the epiblast and hypoblast fuse at the future cranial end of the embryo
-will form the future mouth and oral cavity
2. Cloacal membrane
-fused region at the caudal end of the embryo
-will form anus and associated structures
3. Primitive streak
-epiblast cells converge on the midline of the embryonic disk forming a furrow known as the primitive streak at the future caudal end of the embryo
-the primitive streak establishes a visible longitudinal axis of bilalteral symmetry around which all embryonic structures will organize and align
-probably equivalent to Spemann's organizer in xenopus
THE PRIMITIVE STREAK CONSISTS OF THE FOLLOWING:
a. primitive groove
-shallow valley extending along the length of the streak
b. Primitive node
-a raised circle of cells at the rostral tip of the primitive streak
-(Henson's node)
c. Primitive pit
-a depression in the center of the primitive node

Front 44

Buccopharyngeal membrane

Back 44

1. Buccopharyngeal membrane
-region where the epiblast and hypoblast fuse at the future cranial end of the embryo
-will form the future mouth and oral cavity

Front 45

Cloacal membrane

Back 45

Cloacal membrane
-fused region at the caudal end of the embryo
-will form anus and associated structures

Front 46

Primitive streak

Back 46

Primitive streak
-epiblast cells converge on the midline of the embryonic disk forming a furrow known as the primitive streak at the future caudal end of the embryo
-the primitive streak establishes a visible longitudinal axis of bilalteral symmetry around which all embryonic structures will organize and align
-probably equivalent to Spemann's organizer in xenopus
THE PRIMITIVE STREAK CONSISTS OF THE FOLLOWING:
a. primitive groove
-shallow valley extending along the length of the streak
b. Primitive node
-a raised circle of cells at the rostral tip of the primitive streak
-(Henson's node)
c. Primitive pit
-a depression in the center of the primitive node

Front 47

Primitive groove

Back 47

-shallow valley extending along the length of the streak

Front 48

Primitive node

Back 48

-a raised circle of cells at the rostral tip of the primitive streak
-(Henson's node)

Front 49

Primitive Pit

Back 49

-a depression in the center of the primitive node

Front 50

What forms the definitive endoderm and mesoderm?

Back 50

Epiblast cells replace hypoblast cells to form definitive endoderm and mesoderm

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Front 52

Back 52

PRIMITIVE STREAK STARTS CAUDALLY MOVE BCKWARD (primitive pit moves towards the buccopharyengeal membrane indication)

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On the left, the nascent endoderm is intercalating into the hypoblast. This view shows us the Left on the Left, Right on the Right, and Anterior end of the embryo. On the right, you can see the mesoderm extending away from the primitive streak as indicated by the arrows. At the primitive streak PRIMITIVE STREAK cells undergoing ingressionprimitive ectoderm  ectodermcan call it ectoderm ~day 11cells dividing very quicklycome together and ingress downwardcells intercalate and push aside hypoblastsfirst cells that come through primitive streak replace hypoblast and become true guta few days later when the hypoblast cells are replaced by true endodermstop signals, cells that later come through make mesodermectoderm cells ingress and within an hour have differentiated into mesoderm. Happens quickly! 2 things going on: cell movement and differentiation different set of signals controlling both of those.


__

epiblast cells migrate from the node and primitive streak to replace the cells in the hypoblast and form the definitive endoderm.
-the hypoblast cells recede into the yolk sac and do not contribute to the enbryo
-at the same time another group of cells migrate between the ectoderm and endoderm to form the MESODERM
-this is the INTRAEMBRYONIC MESODERM that actually forms the embryo
-thus the embryo is formed entirely from the cells from the epiblast

Front 54

Notochordal process

Back 54

-epiblast cells that migrate rostrally from the primitive node become the notochordal process which contributes cells to the vertebral column
-once the notochordal process has formed, the primitive streak begins to shrink

Front 55

The following mesodermal structures are formed during gastrulation:

Back 55

1. Notochord process
-epiblast cells that migrate rostrally from the primitive node become the notochordal process which contributes cells to the vertebral column
-once the notochordal process has formed, the primitive streak begins to shrink

2. Prechordal plate mesoderm
-located midline and cranial to the tip of the notochordal process
-induces midline structures such as brain
-cells arise from primitive pit
-note: mesodermal cells do NOT penetrate the regions of the buccopharyngeal or cloacal membranes that remain thin

3. Paraxial mesoderm
-the region of mesoderm closest to the notochord and prechordal plate
-gives rise to the somitomeres, the precursors of the somites that ultimately form the segmented structures associated with the vertebral column
-the first seven pairs of somitomeres DO NOT FORM somites, instead they give rise to the striated muscles of the face, jaw and throat
-the first somites (derived from somitomeres 8-10) appear on day 20 in the region ofthe future base of the skull
-the rest of the somites form in a cranio-caudal progression at a rate of three or four a day and are responsible for the segmented organization of the body

4. Intermediate Mesoderm
-located lateral to the paraxial mesoderm
-gives rise to the urinary system and part of the reproductive system

5. Lateral plate mesoderm
-the outermost layer of the intermediate mesoderm
-splits on day 17 to form two layers that contribute respectively to the structures of the body wall and digestive tract

a. Splanchnopleuric mesoderm
-adjacent to the endoderm
-gives rise to the mesothelial covering of the viscera

b. Somatoplueric mesoderm
-layer adjacent to the ectoderm
-gives rise to the inner lining of the body wall, and to part of the limbs

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Prechordal plate mesoderm

Back 56

-located midline and cranial to the tip of the notochordal process
-induces midline structures such as brain
-cells arise from primitive pit
-note: mesodermal cells do NOT penetrate the regions of the buccopharyngeal or cloacal membranes that remain thin

Front 57

Paraxial mesoderm

Back 57

-the region of mesoderm closest to the notochord and prechordal plate
-gives rise to the somitomeres, the precursors of the somites that ultimately form the segmented structures associated with the vertebral column
-the first seven pairs of somitomeres DO NOT FORM somites, instead they give rise to the striated muscles of the face, jaw and throat
-the first somites (derived from somitomeres 8-10) appear on day 20 in the region ofthe future base of the skull
-the rest of the somites form in a cranio-caudal progression at a rate of three or four a day and are responsible for the segmented organization of the body

Front 58

Intermediate Mesoderm

Back 58

-located lateral to the paraxial mesoderm
-gives rise to the urinary system and part of the reproductive system

Front 59

Lateral plate mesoderm

Back 59

-the outermost layer of the intermediate mesoderm
-splits on day 17 to form two layers that contribute respectively to the structures of the body wall and digestive tract

Front 60

Splanchnopleuric mesoderm

Back 60

-adjacent to the endoderm
-gives rise to the mesothelial covering of the viscera

Front 61

Somatoplueric mesoderm

Back 61

-layer adjacent to the ectoderm
-gives rise to the inner lining of the body wall, and to part of the limbs

Front 62

Somitomeres

Back 62

somitomeres, the precursors of the somites that ultimately form the segmented structures associated with the vertebral column
-the first seven pairs of somitomeres DO NOT FORM somites, instead they give rise to the striated muscles of the face, jaw and throat
-the first somites (derived from somitomeres 8-10) appear on day 20 in the region ofthe future base of the skull
-the rest of the somites form in a cranio-caudal progression at a rate of three or four a day and are responsible for the segmented organization of the body

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Back 63

Front 64

What's going on?
What's the mechanism?

Back 64

-Mesoderm cells spread
Cranio/caudal location of cells leaving node dictate their destiny (fate).
For example…cells that pass directly though primitive node become notochord

Mechanism
-Epiblast cells secrete hyaluronic acid into Ecto/Endo space
-Keeps mesoderm cells from aggregating to soon
-Fibronectin on basal side of ectoderm enhances the ability of mesoderm cells to walk on a substrate
-Cilia on ectoderm near p.n. create proper currents for distribution of intercellular molecules

Front 65

Embryonic cell movements

Back 65

A. Ingression
-entails the movement of single cells away form a layer, such as occurs when epiblast cells migrate to form mesoderm and when ectodermal cells give rise to neural crest cells
*epithelial to mesenchymal transformation --> ingression usually entails alterations in the adhesive properties of cells, for example, changes in cadherin expression are often associated with a transient or permanent change from an epithelial to mesenchymal phenotype

B. Invagination and Involution
-occur when sheets of cells form tubes (eg. neural tube, gut) or acini (glands, lungs)

C. Spreading
-cells spread or re-organize to cover an area of the embryo
-an example of this is convergent extension where cells migrate together and this causes the extension

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What is this process?

Back 66

Once mesoderm cells have gone through the primitive streak and are infiltrate much of the space between endo/ectoderm, they start touching each other and forming clumps of cells. Hyaluronic acid is no longer there to keep them from clumping, so once they start touching mesoderm cells will converge on one-another and then extend resulting in components within the embryo lengthening and narrowing into tube-like structures.

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Kartagener's syndrom

Back 67

Kartagener's syndrome 1:10,000 births
- triad of bronchiectasis, sinusitis, and situs inversus (50% of ICS patients)
-autosomal recessive
-associated with male infertility

-result of cilia that have abnormal dyenin arms so that they don't move properly
-Normally, cilia on ectoderm near p.n. create proper currents for distribution of intercellular molecules
-Sonic hedgehog usually diffuse to left axis, activate nodal.
If this doesn’t happen can get Kartagener's syndrome

In Kartagener's
SHH and FGF-8 then diffuse arbitrarily to both left and right axes leading to embryonic lethality or situs inversus

men come in, cant have children, SPERM TAILS DON’T WORK. Find out they have situs inversus / kartagener’s syndrome

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talk a little more about what's going on here

Back 68

Embyronic mesoderm: notochord processprimitive streak has formed, undergo gastrulationprimitive streak regresses caudally, brings cells through with it forming notochord processprimitive streak normally regresses completely (diseases do occur where primitive streak remains)disappearsnotocord extends caudally

Front 69

Tell me what I need to know.

Back 69

have notochord process (PURPLE) has HOLE in itthere is HOLE inside of itwhat happens as it extends caudally is that the notochord process, like a worm asheres to endoderm and fuses to endodermthis becomes the notochordal plate. LASTS FOR A DAY. REALLY IMPORTANT DAY.What happens is that for a brief period of time, that tissue is in contact w an netirely different envrionemnt (the 2’ yolk sac) this CHANAGES THE TISSUE. Tissue rises again and form the NOTOCHORD. NOTOCHORD PROCESS dif from notochord: 1. no hole 2. can secrete a whole bunch of factors (Shh***** ) notochord process to notochord important transition

Front 70

Induction

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The switching of cells from one developmental pathway to another by the influence of an adjacent group of cells

Front 71

3 types of inductive interactions:

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(gentle reminder -- induction is The switching of cells from one developmental pathway to another by the influence of an adjacent group of cells)

1. Diffusion of soluble signals
-in some cases, cells can secrete factors that diffuse to adjacent cells and are detected by corresponding receptors on the target cells, initiating a signaling transduction
-in many cases, these factors can only diffuse a short distance
-factors that can influence the developmental fate of cells are termed MORPHOGENS
-an example of this is the secretion of Shh by the notochord that induces the differentiation of cells in the somites into chondrocytes

2. Direct cell to cell contact between inducing and responding cells
-There are cases in which the membrane of one cell contains a hormone-like molecule that can make direct contact wit ha receptor on an adjacent cell
-the interaction of these two molecules sends a signal to the target cell initiating a response

3. Contact of cells with the extracellular matrix of other cells
-Cells come in contact with the ECM of other cells and this sends signals
-in tissue culture, cells behave quite differently depending on whether they are grown on a natural substance (collagen) or artificial (plastic)

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Morphogens

Back 72

factors that can influence the developmental fate of cells

Front 73

Diffusion of soluble signals

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Diffusion of soluble signals
-in some cases, cells can secrete factors that diffuse to adjacent cells and are detected by corresponding receptors on the target cells, initiating a signaling transduction
-in many cases, these factors can only diffuse a short distance
-factors that can influence the developmental fate of cells are termed MORPHOGENS
-an example of this is the secretion of Shh by the notochord that induces the differentiation of cells in the somites into chondrocytes

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Direct Cell contact between inducing and responding cells

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There are cases in which the membrane of one cell contains a hormone-like molecule that can make direct contact wit ha receptor on an adjacent cell
-the interaction of these two molecules sends a signal to the target cell initiating a response

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Contact of cells with the extracellular matrix of other cells

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-Cells come in contact with the ECM of other cells and this sends signals
-in tissue culture, cells behave quite differently depending on whether they are grown on a natural substance (collagen) or artificial (plastic)

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The Regulator Hypothesis of Edelman

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Postulates that embryonic morphogenesis is directed by genes that control the timing of the expression of cell adhesion molecules, morphogens and other molecules that are directly responsible for morphogenesis

small differences in the amount and timing of the expression of these molecules accounts for morphological differences between species

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Induction can be controlled by:

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1. feedback loops
-there are situations in which one cell will secrete a factor (A) that induces an adjacent cell to secrete another factor (B) that, in turn, then stimulates the first cell to produce more factor A
-in this fashion, a positive feedback loop can be initiated that determines the fate of these cells
-in other situations, factors can inhibit the production of the same factor by adjacent cells, leading to a punctuate pattern of cells that produce a particular factor

2. Regulator Hypothesis of Edelman
-Postulates that embryonic morphogenesis is directed by genes that control the timing of the expression of cell adhesion molecules, morphogens and other molecules that are directly responsible for morphogenesis
-small differences in the amount and timing of the expression of these molecules accounts for morphological differences between species

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REVIEW NOTES ON THE FATE MAP OF THE EPIBLAST

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p 26 of NOTES

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Signals indicate to invaginate accompanied by CYTOSKELETAL CHANGES in actin and myosin .. Cellular actin and myosinlets cells invaginate When invagination takes place, get neural groove beinging to form. Day 19. neural folds = ridges

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Primitive streak is regressingas it does that notochord transition is taking placeget notochord (is under the neural groove) signals ectoderm above it (via Shh and other signals) to form neural plate

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Signals from notochord continue to communicate ectoderm to invaginate further-directed by cytoskeletal changes and underlying mesoderm proliferation
Neural folds become evident
- Somites begin to arise within underlying mesoderm
Day 20, neuyral folds more evident, somites begin to arise (form the spine essentially .. Muscle and bones)

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Signals from notochord continue to communicate ectoderm to invaginate further-directed by cytoskeletal changes and underlying mesoderm proliferation
Neural folds undergo involution

notochord directs ectoderm cells to form spinal cord

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Initial tissue types in developing embryo?

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ICM------Embryoblast
1. Gives rise to the embryo
Trophoblast
1. Gives rise to placenta and its derivatives

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Uterine tissue undergoes hormone-induced proliferation and differentiation caused by

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1. progesterone (directly)
2. FSH, LH, and estrogen all indirectly influence the uterine preparation for pregnancy

if no fertilization occurred then the uterus sheds

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How do you get the blastocyst cavity?

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how do you get this blastocyst cavity ? Way this happens occurs over and over again in development. Major theme.Basically: on the outside cells, have differentiated into endothelium. Have NA/K pumps. On apical membrane. Pump 2 K into cells and 3 sodiums out. The sodiums will be pumped out into the spaces between those cells. Early on, 12 cell stage in compacted embryo (COMPACTION makes tight junctions, adherns jcns, desmosomes.. Doesn’t let water go back out when it comes in) once you start pumping sodium in, diffusion happens, water goes hwere salt is, starts expanding the space.Sodium, some other electrolytes in blastocoel cavitywhy is blastocoel cavity important?Drawing: blastocyst implanting into endometrihmmetaloproteases like mmp9 and others eat away at epithelium cells. Once they meet endometrium lots of stuff happens.

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Touch endometrium, trophectoderm cells begin to lose their membranes between the cells! When they do that (see light green, dotted membrane) forms SYNCTIOTROPHOBLAST CELLS (one pointed to have 4 nuclei)cytotrophoblasts have membrane intactALSO inner cell mass starts to DIFFERENTIATE: blue cells = epiblase. Yellow cells = hypoblastthey are human terms.Epiblast (aka primitve ectoderm in other animals)hypoblast (aka primitve endoderm in other animals)**primitive is key. NOT gut endoderm white area here is mom’s tissue. Colored tissue is mom’s blood (red). Rest of colored tissue is embryo

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Have implantation taking placeelectron micrograph viewbottom drawing shows interpretaiton of TEM at topsyncytiotrophoblast in dark greencytotrophoblast in light greenpull embryo into endometriumblue tissue = epiblast (primitive something)also have na/k atpaswes on them. FORM ANOTHER CAVITY  proamniotic cavityall colored tissue is embryo except for red (which is mom’sb lood)

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Have entire embryo in endometriumsee uterine epithelium has grown over and healed itselftrophectoderm gets fluid filled spaces – trophoblastic lacunaepiblast at this stage can call bilaminar disc (epiblasts and hypoblasts)proamniotic cavity gets largerhyperblasts, primitive endoderm, migrates along blastocoelic cavity. Imagine 3d ball here, not just flat cut through. DAYS. For exam: know that this isnt happening week 10 .. Get it within a week or so

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Another day in development, day 10/11getting bigger (still microscopic)trophoblastic lacunae getting bigger, more fluid filledalso note that hypoblast has completely migrated around the cytotrophoblast in the blastocoelic cavity .. Called HEUSER’s MEMBRANE: hypoblast cells and ECM proteins they secrete (two components of this membrane). Once the primitive endoderm has encircled.. NOW CALLED PRIMITIVE/PRIMARY YOLK SAC (will be 2’ yolk sac eventually)

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? Starting w/ tropectodermmom’s blood is started to enter the trophoblastic lacunae cavity gets biggerthen have extraembryonic reticulum. Where is this from? Space between heuser’s membrane and cytotrophic blast and secreting stuff (RELISTEN) and forms gelatenous stuff. Secrete ECM between the two.This is around days 10-11-12

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The extraembryionic reticulum signals .. Provides signals for primitive ectoderm/epiblast to differentiate at least at that portion of the epiblastcells become EXTRAEMBRYONIC MESODERM (mesoderm that’s part of the placenta) take home: extraembryonic mesoderm come from EPIBLAST. Migrate along heuysers membrane and cytotrophoblastcheck out mom’s blood all over the place another day goes by, have extraembruonic mesoderm all over the place, completely coveringwhat odes that do? Leads to next important structural change. Cells can no longer secrete ECM proteins bc theyre blocked by mesoderm. The ECM in between breaks down, evenutally breaks down. Whole thing is getting bigger but has no more protein to supply, replaced by saline

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Have primitive yolk sac beginning to get PINCHED OFF. Hypoblast (?) cells growing and yoc sac getting bigger. Pinches off. The whole thing is getting largerday 13what did extraembryonic reticulum become? The CHORIONIC CAVITY. Important cavity. Embryo is now growing into this structure

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primary yolk sac pinches off furthter, floats away to other sdie, adheres, degenerates
leaves behind 2’ yolk sac
Why does this all have to happen?Cells are different, capable of a different fxn. One fxn is to make vascular cells .. Vasculargenesis where you get first blood cellsimportant structures: extraemrbyonic retiulm becomes chorionic cavity this is what embryo grows into

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Embryo are the bilaminar diskhyperblast and epiblast (yellow and blue ,resp)proamniotic cavity inside the blue area at bottom, blow it up a littleall trophoblastic lacuna are full of mom’s blood, which is NOT interacting w embryo

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PRIMARY STEM VVILLUS where you start to see thickingChorionic cavity = top whitebottom white = endometriumall the cells in between are contacting each other and sending signals to each other100s of dif types of signalstell cells to proliferateif you have thickening of cells in yellow, tell extraembryonic mesoderm to proliferate w it Secondary stem villusOnly in specific areas cytortophoblast cells tell extraembryonic mesoderm to proliferate with itno membranes broken, continuous membrane of synctiotrpoblastgrows toward endometrial sidethen 3’ stem villus

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Clinical pathology between day 4 and 21ectopic pregnancymost of the time 54% its in the ampular region, but can also happen in cervical region and in interstitial regionalso isthmic region
Can ALSO have INTESTINAL AND RECTAL implantations. Follow this with ultrasound  vaginal bleeding and abdominal painnormally ultrasound done around week 16, but symptoms for ectopic pregnancy happen before that **Growth of embryo can result drawing maternal blood vessels to it to provide nutrients. These blood vessels usually burst resulting in internal bleeding. If untreated, can be lethal to mother.

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Preeclampsia

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Pre-eclampsia
-A syndrome recognized by shallow implantation
-Occurs in 5% of all pregnancies
-20% of all serious birth complications
-especially in first preg.
-overweight women
-IVF with donor egg
-Cause is not really known (until a couple of years ago -- sFlt1)
-can be genetic predisposition
-Creates problems in both mother and fetus – mostly in mom
Mother: throughout pregnancy (mostly seen in 3rd trimester)
1. Hypertension-can be very serious
2. Proteinuria – protein in urine
3. Liver inflammation
4. Edema
5. clot-plugging platelets depleted
6. Severe cases lead to swelling in the brain, convulsions and possibly coma.
At that point the syndrome is termed Eclampsia
Fetus:
1. Usually results in premature birth


WHAT CAUSES IT?!
- Flt-1 (VEGF receptor) found on endothelial cells-
responsible for blood vessel growth.
ALSO found circulating in blood (called sFlt-1).

- placental growth factor (PLGF) produced by placenta and binds Flt-1
to enhance blood vessel growth during
pregnancy especially during 3rd trimester

Clinical Findings: Blood from women who developed pre-eclampsia was compared to blood from women who did not.
-5 weeks before disease onset sFlt-1 levels rose significantly while PLGF levels significantly dropped

Conclusion: sFlt-1 in the bloodstream hijacks PLGF leading to deterioration of existing blood vessels and inhibition of new ones in placenta and other organs such as kidneys, liver, etc. (last bit leads to edema)

Treatment: Flood mother with PLGF to compensate

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Hydatiform mole (complete)

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A. Background
1. No Fetus
2. Conceptus Comprised Only of Placental Membranes
3. Occurs in 0.1-0.5% of Pregnancies
4. Most Common in Women Under Age 25
5. Hydatis-Cyst or cyst-like; Mole-Fleshy growth

B. Symptoms
1. Vaginal Bleeding
2. Hypertension
3. Edema
4. Abnormally High Levels of Plasma hCG ** KEY
5. Complete moles usually abort early (by week 10)
Remnants may remain\

C. Identification requires cytogenetic analysis (eg. chromosome count, PCR)

A. Mole Can Be Aborted or Surgically Removed
1. Persistent Trophoblastic Disease
2. Residual Trophoblastic Tissue Can Form Tumor, Which Can Become Malignant
a. Invasive Mole (Mort. Rate in 1980 was 60%. Now 0%
b. Choriocarcinoma (Mort. Rate 1980 was 100%. Now 20%

B. Reasons for Drop in Mortality
1. Highly sensitive assays for plasma hCG
2. Cytogenetics and PCR to I.D. Chromosomes in Trophoblast
3. New Chemotherapies

Complete mole: diploidoocyte + sperm  sperm pronucleus divides  diploid nucleusoocyte + 2 sperm  two male pronucleiDON’T LOSE FEMALE PRONUCLEUS. IT NEVER FORMED IN FIRST PLACE. Spindle apparatus, all of female chromosomes went into 2nd polar body. Fertilization can still take place, but get all male chromosomes

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Partial hyadtiform moles

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A. Background
1. No Fetus
2. Conceptus Comprised Only of Placental Membranes
3. Occurs in 0.1-0.5% of Pregnancies
4. Most Common in Women Under Age 25
5. Hydatis-Cyst or cyst-like; Mole-Fleshy growth
B. Symptoms
1. Vaginal Bleeding
2. Hypertension
3. Edema
4. Abnormally High Levels of Plasma hCG ** KEY
5. Complete moles usually abort early (by week 10)
Remnants may remain
C. Identification requires cytogenetic analysis (eg. chromosome count, PCR)
A. Mole Can Be Aborted or Surgically Removed
1. Persistent Trophoblastic Disease
2. Residual Trophoblastic Tissue Can Form Tumor, Which Can Become Malignant
a. Invasive Mole (Mort. Rate in 1980 was 60%. Now 0%
b. Choriocarcinoma (Mort. Rate 1980 was 100%. Now 20%
B. Reasons for Drop in Mortality
1. Highly sensitive assays for plasma hCG
2. Cytogenetics and PCR to I.D. Chromosomes in Trophoblast
3. New Chemotherapies

INCOMPLETE / Partial hydatiform MOLE: triploid
2 sperm and keep female pronucleus there. May be XXX, XXY, or XYY-result in further embryonic development than complete moles-spontaneous abortion usually occurs in 2nd trimester-rarely, an abnormal fetus is born. Does not survive.

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Prader-WIlli

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A. Pathology and Symptoms
1. CNS Malformations
2. Impaired Body Control
3. Mental Retardation
4. Short Stature
5. Insatiable Appetite  a. Starting at 2-5 years  b. Obesity  6. Behavioral Difficulties  a. Temper tantrums, Stubborness
B. Incidence
1. 1 in 15,000 live births

CAUSED BY:
deletion of a portion of chromosome 15 at site q11-q13 on the MALE chromosome.

NOTE: Prader-Willi and Angelman’s Syndrome Result from the Same Chromosome Deletion at 15q11-q13P.W. Occurs when the deletion is inherited from the father
A.S. Occurs when the deletion is inherited from the mother

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Angelman's syndrom

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CAUSED by a deletion of a portion of chromosome 15 at site q11-q13 on the FEMALE chromosome

Pathology and Symptoms
1. Developmental Delay
2. Little or no Language Skills
3. Movement or Balance Disorders
4. Happy Demenor

B. Incidence
1. 1 in 15,000 live births

NOTE: Prader-Willi and Angelman’s Syndrome Result from the Same Chromosome Deletion at 15q11-q13P.W. Occurs when the deletion is inherited from the father
A.S. Occurs when the deletion is inherited from the mother

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REVIEW LAST FEW SLIDES LECTURE 25 ON GENOMIC IMPRINTING. REVIEW NOTES FROM FIRST TEST ON SITES OF IMPRINTING/BIOCHEMICAL BASIS>

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REVIEW LAST FEW SLIDES LECTURE 25 ON GENOMIC IMPRINTING. REVIEW NOTES FROM FIRST TEST ON SITES OF IMPRINTING/BIOCHEMICAL BASIS>

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Besides hydatiform moles and PW/AS, what are some other clinical consequences of genomic imprinting?

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Clinical Consequences of faulty genomic imprintin
A. Severity & age of onset of genetic disease depends on parent who had the mutation
1. Spinocerebellar ataxia
2. Myotonic dystrophy
3. Neurofibromatoses I and II
4. Huntington’s Chorea
5. Wilm’s Tumor (caused by WT-1 gene)

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Meckel's diverticulum

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an anomoly of the digestive tract resulting from a yolk sac that does not dissolve

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Where is the major site of hematopiesis?

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extraembryonic mesoderm forming the outer layer of the yolk sac

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Decidual reaction

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decidual tissue came from endometrium. Call it decidual because the cells makin gup the white area have undergone massive proliferation as compared to endometrium 10-15 cm away that has not undergone that much proliferation

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Day 21 Now have EMBRYONIC BLOOD VESSLES enmeshed in EXTRAEMBRYONIC MESODERM this is where they come from! – this is what gives rise to fetal blood vesselesthe spaces are partly responsible/help allow mom’s blood to have some force/pressure being squirted into trophobastic lacuna note arrows .. Lets water, gucose to get across the membrane and into embryonic blood streamremember mom and baby blood not supposed to mix

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Here the chorionic cavity is on the bottom,decidua tissue is on the top (opposite from other image) cytotrophoblast are cytotrophoblast dark green synccytiotropblastCHANGE IN TERMINOLOGY: INTERVILLOUS SPACE (instead of tropoblastic lacuna). Maturation. Can see these using ultrasounds. Important to look at at 16-17 weeks. Do first ultrasound look not just at fetus itself, also look at placenta to make sure structures like this are nice, plump, full of blood

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Here the chorionic cavity is on the bottom,decidua tissue is on the top (opposite from other image) cytotrophoblast are cytotrophoblast dark green synccytiotropblastCHANGE IN TERMINOLOGY: INTERVILLOUS SPACE (instead of tropoblastic lacuna). Maturation. Can see these using ultrasounds. Important to look at at 16-17 weeks. Do first ultrasound look not just at fetus itself, also look at placenta to make sure structures like this are nice, plump, full of blood

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chorionic cavity at the top, decidua at the bottom note mom’s blood vessles bringing oxygenated blood to intervillus spacesblood is then pushed with pressure into intervillus spaces, bathe synctiotrophoblastblood is pushed through into the veins (maternal in uterus)work way up, see that the CHORION is considered the FETAL PORTION OF THE PLACENTAthere are actually 2 portions to the placenta: the embryo’s portion (syncstiotrophobloast, cytotorpoblst, extraembryonic mesoderm)and mom’s part – chorion

Also have umbilical arteried and veins ** note that artery has deoxygenated blood FROM fetus and vein has oxygenated blood to the fetus. Has to do w/ blood in respect to MOM HEART.

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barriers that keep mom and baby's blood from mixing?

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cytotrophoblastic cellssynctiotrophoblast cellsextracellmatrix between all those cells
also enodthelial cells – cell membranes of the endothelial cells that make up the capillaries/blood vessles from the embryo.

These are all barriers from mom and embryos blood mixing

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Cells that can shed to mom's blood

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Synctotropoblast and cytotroblast cells can shed to mom’s blood

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1’ 2’ and 3’ stem villusCHORIONIC PLATE cells of cytotrophoblast that is next to chorionic cavityalso have cytotrophoblastic shell (those are near intervillous space)spiral artery from mom are more or less injecting blood into intervillous space, bathing 3’ stem villus.STEM VILLOUS CONTINUE TO BRANCH UP UNTIL MIDDLE OF LAST MONTH OF PREGNANCY. spiral arteries from mom also proliferate (with the help of plgf etc)maternal blood does not mix w fetal blood. The barriers that keep them from mixing are numerouscytotrophoblastic cellssynctiotrophoblast cellsextracellmatrix between all those cellsalso enodthelial cells – cell membranes of the endothelial cells that make up the capillaries/blood vessles from the embryo. These are all barriers from mom and embryos blood mixing
Synctotropoblast and cytotroblast cells can shed to mom’s blood when bloods do mix not the end of world but not necessarily a good thing

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SEM this is chunk of tissue coated in gold, silver different metals chorionic plate is at bottom of this imagemain stem villus coming upwhite arrows are terminal villimain sem villusthen have cytotrophoblastic chelldark area is all filled w mom’s blood. Rest of structures are fetus’s tissue

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**BE FAMILIAR W THIS IMAGE FOR THE EXAM. Not just labeling for the exam, give FUNCTION of what’s going on. Eg. chorion frondosum = functional part of chorion (chorion = embryo’s portion of placenta). This is the area that more related to where the umbilical cord is associated. Mom blood into intervillous spacethe chorion leave (leah-ey- vee) closer to the external part of uteruswhite area at bottom is the lumen of the uterus. This hasn’t grown yet, once it does the lumen of the uterus more or less disappearsnote chorion leave normally breaks downdecidua capsularis. Take mom’s portion of the placenta****decidual = mom’s portion of the placenta. If you break it down a bit further, the decidua capsularis is on the outer embryonic side of the placenta. Chorionic plate borders the chorionic cavity outer cytotrophoblastic cells borders the decidua

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FUNCTIONS OF THE PLACENTA

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1. TRANSPORT
2. BARRIER
3. PRODUCT HORMONES

A. Transport
1. Gases O2, CO2, CO (if you’re exposed to CO)
2. Water, Glucose, Vitamins, lipids
3. Hormones
a. hCG (feeds back on the corpus luteum in early stages), Corticosteroids (from mom) – stress hormones can get through and affect baby. If mom is under a lot of stressw it can affect embryo
4. Electrolytes (NaCl, CaCl2, MgCl, etc.)
5. Maternal antibodies
a. Selective uptake of IgGs
neonatal Fc receptor (Fc receptors binds to Fc portion of ab from mom’s  blood. Brings them across and deposit into embryo’s blood. Dunno how  this happens exactly. Can see it when you label certain ab. Sets up passive  immunity
b. Sets up Passive Immunity against diptheria, smallpox, measles, but not chicken pox,  and whooping cough. (Fc receptors for those not found on syncsitotrophoblast)
6. Drugs and their metabolites
7. Waste products.
Barrier
1. Cutoff around 100,000 Daltons
a. excludes most viruses (bigger than 100,000 daltons) and bacteria. What about  Cells??
C. Produces hormones
1. hCG (syncitiotrophoblasts)
2. PLGF
3. local production of Indoleamine 2,3, deoxygenase (IDO) destroys tryptophans on maternal T cells rendering them inactive as they approach the placenta (nature paper. Renders T cells locally inactive. Makes embryo safe from mom’s immune system)
4. Somatomammotropin (gives fetus priority of maternal blood glucose. Can cause mother to become temp. diabetic)

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What's the cutoff size of things that can cross the placenta?

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1. Cutoff around 100,000 Daltons
a. excludes most viruses (bigger than 100,000 daltons) and bacteria. What about  Cells??

CANCER CELLS CAN CROSS --> Melanomas, leukemias, and lymphomas (**blood types of cancer) have been shown to cross the placenta resulting in the fetus developing cancer. – don’t know whether its active or passive)

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Blood flow by week 18?

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500 mls / min

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The decidua basalis – light colored orange is MOMS portion of placenta. This is portion that borders the CHORION FRONDOSOMthe decidua parietalis – this is the mom’s portion of the placenta, hasnt really interacted yet w embryo’s portion of the placenta yet. This is on the OPPOSITE SIDE OF UTERUS FROM WHERE EMBRYO HAS EMPLANTEDdecidua capsularis .. This is the decidua cells that interacts specific with chorion laevechorion = embryo’s portion decidua = mom’s portion *****choironic cavity although it’s getting larger is beginning to shrink is size because the amniotic cavity is filling up the space of the chorionic cavity. It’s separated by the amniotic sac (arrow to it)do ultrasound stuff w fluid black, so amniotic sac and chorionic cavity would both be black.2’ yolk sac also degenerates over time. The functionn of the yolk sac has no more function by 10 weeksUTERINE CAVITY .. Technically your embryo is still technically in the endometrium. Not in the uterine cavity. Did not grow just by binding to the uterine epithelium. It INVADED INTO ENDOMETRIUM and made all these structures and now this is just growing. The decidual capsularis is the border that is keeping it within the endometrium of the uterus amniotic sac fuses to chorionic plate/laevedecidua capsularis, decidua paritalis, chorion laeve FUSE on the opposite side of the uterus. The amniotic sac, which was small has also fused to the chorionic plate, to the chorion laeve. Still exists, the amniotic sac is still there, chorion laeve is still there, decidua paritalis and decidua capsularis is still there. All demarcated by membranes. Chorion frondosum, where all of mom’s blood is being injected into. the decidual paritalis, all these other tissues still there, demarcated by membranes. chorionic frondosum is mom’s blood injected here

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Note fetal circulation (2 arteries 1 vein)amniotic cavity at this point has probably taken over chorionic cavity If you don’t have many tert stem villi in the wayt, decidua basalis cells can grown between tertiary vicilli, form structure called SEPTUM (arrow)– VERY IMPORTANT STRUCTUES. what’s so important about septum you ask? Spiral arteries and veins still doing their thing. The septum, however, are important because you can compare area that does not have 3’ stem villus (see 2 septum far apart) with area that has 3’ stem villus present. If septum wasn’t there, it would be pushed into that area and be forced to go upwards to the chorion plate. Without septa, really difficult to get oxygenated blood to the chorionic plate. Septa super important. Other importance of septum is when you’re looking at this stuff more macroscopally.

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after birth, have the afterbirth comprised of both mom’s portion of placenta (decidua basalis) and the chorion the afterbirth all the colored placenta tissue is born about 20 minutes laterwhat comes out looks like whats on this slidefirst thing obgyn does is to look at the structure, the decidual side. If removes the decidua basalis have the remnents of small septum. , .. Sometimes have remnants of big deep sections, sometimes decidua basalis grows almost all the way down to choreonic plate. big septum that’s called cotyledon.MUST look like this when it comes outif you have area where cotyledons are collapsed or don’t look healthy, that’s a sign that you need to look at baby for issues – first thing obgyn does anyway is listen to the heart. If it’s there, have a good beat, great. When afterbirth comes out and cotyledons are not in good shape, need to listen to heart more closely – embro/fetus was NOT getting enough oxygenated blood to side opposite chorion, so FETUS’ HEART WORKS HARDER  GET VALVE PROBLEMS. NEED TO LISTEN FOR A MURMOR. If there is a relatively bad murmor, may need to do surgery on baby to do valve repair main issue for baby heart mumor: bad blood flow from placentasmall tiny septum.. Also deep septum make cotyledon.

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Amnion

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Comprised of epithelial cells (from epiblast and mesoderm) a few layers thick and is the inner most fetal membrane
1. Fluid
a. Composed of water from maternal blood that diffuses through intervillus spaces. Other components include electrolytes, proteins, lipids, carbohydrates, desquamated fetal epithelial cells.
b. Entire volume is replaced every 3 hrs. diffusion
c. By 37 weeks the amniotic sac contains 800-1000mls of fluid
d. Functions to cushion the embryo from impacts, maintains consistent temp., acts as barrier to infections, and allows a consistent environment.
e. Also functions to bath the external areas within the embryo (e.g., lungs, G.I. Tract).

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amniocentesis

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Amniocentesis
Amniocentesis is carried out when there are medical concerns of the fetus.
For the detection of, for example, Tay Sachs disease, down syndrome.
A couple may want to know the sex of their child
Chromosomal analysis will reveal trisomy

Removal of small amount of amniotic fluid via needle
Not usually done before 13-14wks (not enough fluid)
Amniotic fluid contains cells that have been sloughed from embryo
Fluid: examine proteins present (e.g., alpha-fetoprotein signals neural tube defects)
Cells: sex (e.g., X chromosome; trisomy) or genetic defects (e.g., PCR/enzymes for Tay Sachs)

Take out, spin down, isolate cells. Breaking amnion risks for premature birth, can do other things too. If that baby flips, a leg can go outside of that hole, would amputate the leg if its outside of the amnion. Hole pretty small, heals fast, can cauterize when you pull it out. Not really concerned about fluid loss.

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Umbilical cord

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-Derived from extraembryonic mesoderm at posterior end of disc
-Blood vessels undergoing angiogenesis enter the connecting stalk around week 3
-3-4 weeks: see extraembryonic ectoderm and extraembryonic mesoderm begin to fold upon connecting stalk. In connecting stalk have 2’ yolk sac begin to be squeezed out. Note the embryo’s body. In umbilical cord can see ectoderm and extramebryonic mesoderm covering the entire connecting stalk. ISSUE WITH IMAGE: arteries are colored red, should be blue, veins blue should be red.


Here is umbilical cord, large structure early on compared to embryo. By week 6-8 its covered by amniotic membrane. The intestinal endoderm, true gut, can enter into the umbilical cord. If it is NOT retracted back, get umbilical hernia. yellow tissue that intestinal loop is pointing to is true gut endoderm from primitive tissuethen have true gut/hypoblast. Right at star. One cell difference.

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Color Doppler Ultrasonogram
of Umbilical Circulation

A Color Doppler ultrasonogram measures the blood flow through the umbilical vein and arteries.
Flow Velocity Waveforms (FVW) are visualized by a sonogram detector, which measure direction and resistance of blood flow. (not pressure, upper and lower limits are not measured)
A typical set of FVWs in an umbilical artery from an 8 week embryo is seen in ‘A’
FVWs in the umbilical vein in ‘B’ at 8 weeks are much stronger relative to the arteries. Why? – larger, more volume
By week 12 the arteriole FVWs contain an additional wave called an End Diastolic Velocity (EDV – red arrows) suggesting increased resistance in the arteries. If they aren’t there, can make an educated guess that there may be some problems with blood flow in the placenta.
These can be used as diagnostic tools for determining blood flow to and from the embryo/fetus

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Receptors responsible for vasculo and angiogenesis

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Fibroblasts make vegf, binds to vegf receptor.Flt1 is receptor. Sflit = soluble flit, floating around in mom’s bloodalso flk1these two receptors for vegf help define the paths these cells take. Do they become Hemangioblasts that then become rbc or do they become capillary? Plgf helps to drive this too

**recall that high levels of sflit and dropping levels of pglf indicate preeclampsia
Treatment: Flood mother with PLGF to compensate

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Dizygotic twins

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1. Formed as ovary releases two eggs. Each are fertilized by a single sperm
Usually develop separate placentas (A)
Chorions can fuse as in (B)
a. Can lead to erythrocyte mocaicism (when that happens fetus is fine but they can have erythrocyte mocaicmmom is A dad is O, baby left is A baby right is O, can have type A and O in blood streams. Will always have that. NOT A PROB WHEN THIS HAPPENS EMBRYONICALLY )

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Monozygotic twins

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Identical, formed from one egg and sperm

Can result in three different arrangement of fetal and placental membranes
1. Embryo possible splits prior to blast formation-Results in separate compartments
-->embryo possibly splits prior to blastocyst formation –what is likely happening is that embryo hatched prior to blastocyst formation/differentaition and embryo splits into two. Can still develop w/o a zona. Embryos go into uterus and impant in separate spots
2. ICM spilts-Results in shared placenta` and chorionic sac. this is usually what happens
3. Gastrula splits-Results in Shared placenta, chorionic sac, and amniotic sac . Doesn’t happen often. Is a defect in signaling mechanisms (shh, etc.) the entire placenta is shared when this happens.

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What happens to the embryo at week 6?

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Between week 6-8 the entire structure is surrounded by amniotic membrane creating the primitive umbilical chord
1. Also at this stage, excess intestinal endoderm can enter the chord resulting in an umbilical hernia, but usually are withdrawn back into fetal abdomen by Week 24-26

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Where does vasculargenesis begin?

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Vasculargenesis begins in yolk sac. Get blood islands that expand to make vessels. Enter and start combining with other blood islands forming in the extraembryonic mesoderm. This is where initialization of blood vessels form. 2’ yolk sac. (not 1’.. This is long gone).

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What forms the amniotic cavity?

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Na/K atpase pump

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What happens to the embryo at week 7?

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A. This embryo is enmeshed in its fetal membranes.

C. Within the umbilical chord, the arteries and veins are enmeshed in a proteoglycan-based substance called Jelly of Wharton – prevents arteries and veins from being clamped off

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Jelly of wharton

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Within the umbilical chord, the arteries and veins are enmeshed in a proteoglycan-based substance called Jelly of Wharton – prevents arteries and veins from being clamped off

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Clinical problems related to membranes and their fluids?

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Umbilical Chord Abnormalities
1. Chord can wrap around neck causing difficulties
2. False Knots can cause decreased blood flow
a. Cardiac and vascular defects
Amniotic Banding
1. Results from amniotic membrane tears allowing legs, arms, fingers, head or face to become constricted. May result in amputations or craniofacial deformities.

Amniotic Fluids
1. Hydramnios or polyhydramnios
a. Results from excess amniotic fluid.
i. Can result in maternal diabetes
ii. Anencephaly
iii. G.I. Defects -- too much fluid in GI tract, extends cells. Bad
2. Oligohydramnios
a. Results from decreased amounts of amniotic fluid
i. Can cause lung and G.I. Deformities. Problems if there isnt enough fluid in the lungs of the embryo

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Amniotic Banding

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1. Results from amniotic membrane tears allowing legs, arms, fingers, head or face to become constricted. May result in amputations or craniofacial deformities.

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Hydramnios or polyhydramnios

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a. Results from excess amniotic fluid.
i. Can result in maternal diabetes
ii. Anencephaly
iii. G.I. Defects -- too much fluid in GI tract, extends cells. Bad

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Oligohydramnios

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a. Results from decreased amounts of amniotic fluid
i. Can cause lung and G.I. Deformities. Problems if there isnt enough fluid in the lungs of the embryo

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Placenta Accreta:

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Lack of decidua basalis

can lead to various Intrauterine Growth Restrictions (IUGRs)
Fetal demise (morbidity)
Perinatal distress
Low birth weight (smoking)
Perinatal asphyxia (low or lack of oxygen to fetus)
Cognitive abnormalities
Cerebral palsy
Cardiac anomalies (valve disorders)

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Placenta Percreta

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Villi penetrate myometrium
Into endrometrum
Not good. Goes way past the endometrium

can lead to various Intrauterine Growth Restrictions (IUGRs)
Fetal demise (morbidity)
Perinatal distress
Low birth weight (smoking)
Perinatal asphyxia (low or lack of oxygen to fetus)
Cognitive abnormalities
Cerebral palsy
Cardiac anomalies (valve disorders)

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IUGRs

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Intrauterine Growth Restrictions (IUGRs)

Fetal demise (morbidity)
Perinatal distress
Low birth weight (smoking)
Perinatal asphyxia (low or lack of oxygen to fetus)
Cognitive abnormalities
Cerebral palsy
Cardiac anomalies (valve disorders)

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How do cadherins influence development?

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Controlling expression of cadherins (cell adhesion molecules) spatially and temporally dictates how and when cells adhere to one another. Change that adhesion by regulating cadherins may control the body plan of an animal.