Exam 1 (Embryology) Flashcards
What is the main event in the pre-embryonic period?
Implantation!
What events mark the beginning and end of prenatal stage and the what is the time frame?
From fertilization to birth (day 1 - all the way to week 38 [full fertilization age])
Gestational (obstetric) v. Fertilization (actual) age
Gestational (obstetric) age: measured from the first day of the last normal menstrual period (LNMP). Used to communicate with patients.
Fertilization (actual) age: measured from the time of fert. 2 weeks is deducted from gestational age. Full term = 38weeks fert. age.
When is the greatest risk of spontaneous abortion? Also, what may cause a quarter of these spontaneous abortions?
~50% of all are spontaneously aborted during the pre-embryonic period. (Think Implantation)
~25% of spontaneous abortions are because of chromosomal abnormalities that originate during meiosis.
When is the greatest risk of birth defects? Also, what causes ~10% of these birth defects?
Embryonic stage is the period in which most birth defects occur (organogenesis).
~10% of major birth defects are caused by chromosomal abnormalities that originate during meiosis.
Conceptus
All structures that derive from a fertilized egg. Even structures that will not be part of the newborn infant (i.e., placenta).
Induction
Initiation of embryonic cell migration/differentiation through signaling. (cells are “told” to “move” and/or “change” into something else.
Mesenchyme
Gelatinous tissue containing undifferentiated migratory cells. (embryonic connective tissue).
Teratogen
An agent that causes developmental malformation (i.e., alcohol).
Spermatogenesis
Occurs in the testes and begins during puberty and is continual until death. Starts with a primary spermatocyte after DNA replication (4n) –> ME I separate homologous pairs (2n [haploid]) ME II separate sister chromatids (1n [haploid]). Produces: 4 spermatids (immature) that mature into sperm (~86 days).
Oogenenis
DNA replication of the primary oocyte begins prenatally. The primary oocyte after DNA replication BEGINS MEI PRENATALLY. Primary oocytes are stuck in MEI and only finish it after ovulation. Then the secondary oocyte is stuck in MEII, until fertilization, then MEII finishes. (cyclical, ~12-45 yrs) produces 1 oocyte, 3 polar bodies.
Meiosis is important because?
1) Forms diploid cell (zygote) at fertilization; 23 maternal + 23 paternal.
2) Allows random assortment of maternal and paternal genetic material.
3) Introduces variation by recombination of genetic material (crossing over).
Nondisjunction + its clinical correlations
Chromosome pairs do not separate properly during meiosis/mitosis. Down Syndrome (trisomy 21) Turner Syndrome (45, X monosomy) Klinefelter syndrome (47 XXY trisomy)
Pathway of sperm all the way to fertilization
Testes (spermatogenesis) –> Epididymis (storage or sperm, where sperm become motile; sperm released during ejaculation) –> Ductus Deferens (aka vas deferens) –> ejaculatory duct –> urethra –> Vagina –> Uterus (cervix –> body) –> uterine tubes (ampulla [“amped” for fertilization] = where fertilization normally takes place)
What must occur before sperm penetrates the corona radiata?
Capacitation = 7 hr conditioning of sperm
- necessary for fertilization
- glycoprotein coat on sperm head is removed
Zona Pellucida (ZP) v. Corona Radiata
Corona Radiata = supporting cells
ZP = extracellular matrix
Typical location of fertilization
ampulla of uterine tube
“amped” for fertilization
Sequence of events during fertilization (version 1)
1) 300-500 capacitated sperm reach the oocyte
-only 1 fertilizes it, else polyspermy
-enzymes allow passage through CR
-oocyte arrested in ME II (ME I was completed at ovulation)
2) Acrosome rxn: “enzymatic drill” though ZP
+ Zona rxn: ZP hardens to prevent polyspermy.
3) Sperm membrane fuses w/ oocyte membrane
+ oocyte completes ME II
Sequence of events during fertilization
1) Capacitation
2) CR penetration
3) Acrosome and Zona Rxns
4) Fusion of plasma membranes, oocyte completes ME II
5) Zygote is formed, sex is determined.
Fertilization: Clinical Correlation
15-30 of couples are infertile
Males: insufficient sperm numbers, poor motility. . .
Females: pelvic inflammatory disease (PID), ovulation disorders, endometriosis, cysts, fibroids
In Vitro Fertilization: oocytes are harvested laparoscopically, fertilized, and the implanted. (success is age-dependent)
What are the week 1 events?
1) Cleavage: mitotic devisions that for cells called blastomeres. (begins immediately after fertilization)
2) Compaction: tighter blastomere intracellular adhesion, forms morula = inner/outer cell mass. (~day 3) (enters uterine body at day 4)
3) Cavitation: unterine fluid pumped into morula to form blastocyst.
4) Hatching: blastocyst hatches from the ZP
5) Implantation: blastocyst implants in endometrium of uterine wall (day 6)
Cleavage
Mitotic devisions that form cells called blastomeres. This begins immediately after fertilization. It increases the cell number, but it decreases the cell size. Nondisjunction during this mitotic devisions = mosaicism.
Mosaicism
Nondisjunction during cleavage: generally less severe; i.e., mosaic down syndrome.
Compaction
tighter blastomere intracellular adhesion to form the morula. (~day 3) This allows cells to communicate, work more closely and direct their fates.
Results in formation of inner and outer cell mass.
Cavitation
Uterine fluid pumped into morula forming the blastocyst (after day 4). This results in the inner cell mass become the embryoblast and the outer cell mass to become the trophoblast. Now there is some directionality: embryonic pole: end with embryoblast as well as abembryonic pole (opposite end.
Morula
ball of cells formed from blastomeres via compaction. these cells have tighter intracellular adhesion than blastomeres. The morula is what enters the uterine body at day 4. The MORULA is “4” the uterine body.
Blastocyst
Formed by cavitation (uterine fluid being pumped into the morula ~after day 4). Blastocyst has a cavity called a blastocyst cavity, and the inner/outer cell masses of the morula becomes the embryo/trophoblasts of the blastocyst. During week 2 the embryoblast becomes the epiblast and hypoblast while the trophoblast becomes the cytotrophoblast and the syncitiotrophoblast.
Where is the embryoblast derived from? By what process and when? What does it become?
Inner cell mass of the morula. Cavitation makes a cavity in the morula to make the blastocyst cavity within the blastocyst. This happens sometime after day 4, because the morula enter the uterine body at day 4. It becomes the epiblast and hypoblast during the formation of the bilaminar disc”the week of twos”.
Where is the trophoblast derived from? By what process and when? What does it become?
The trophoblast derives from the outer cell mass of the morula. Cavitation brings in uterine fluid into the morula to make the blastocyst, which forms the trophoblast, which happens sometime after day 4 when the morula enter the uterine body. The trophoblast becomes the cytotrophoblast and the syncitiotrophoblast.
Hatching and when does this happen? Also, what can occur if hatching occurs too early . . . or late?
blastocyst hatches from zona pellucida (ZP prevents implantation) This happens during day 6 right before implantation. If it hatches too early an ectopic pregnancy may occur (implantation outside of the uterus) If implantation occurs near the cervix, it may lead to placenta previa (placenta blocking the cervix, which often requires C-section)
Ectopic Pregnancy
Implantation occurs outside of uterus. Most common place occurs at the uterine tube near the ampulla.
Placenta Previa
Implantation near the cervix may lead to this, where the placenta obstructs the cervix and often requires a C-section. During this time nourishment is provided by the uterine gland secretions.
What provides nourishment during implantation?
Uterine gland secretions from the endometrium.
Implantation
Trophoblast at the embryonic pole of the blastocyst invading the uterine wall at day 6.
What are the main events of week 2?
Week 2 = “The week of Twos”
1) Implantation completed: uteroplacental circulation is establish (vascular lacunae [“lagoon”])
2) Bilaminar disc formed: embroblast differentiates into 2-layerd disc. (epiblast and hypoblast)
- trophoblast also becomes cytotrophoblast and sycitiotrophoblast.
- primary yolk sac (pYS) and Amniotic cavity (AC) are formed.
- then the trophoblast becomes the syncitioblast and cytotrophoblast.
- then the extraembryonic mesorderm (EM) forms adjacent to hypoblast (exocoelemic membrane).
- spaces appear in EM, unite to form a single, large extraembryonic cavity (EC)
- part of the pYS is “pinched off” to for the secondary/definitive yolk sac. (sYS)
When does implantation begin and complete?
Begins at day 6 right after hatching of blastocyst from the ZP. It is complete during week two, when uteroplacental circulation is established (via the vascular lacunae [vascular “lagoons”])
From what is the bilaminar disk formed, when, and to what?
From the embyoblast of the blastocyste. This is during the beginning of week two, after implantation is complete. It becomes the epiblast and hyopblast. (these form the embryo/fetus and amnoin)
What does the trophoblast become?
1) cytotrophoblast
2) syncitiotrophoblast
Happnes after implantation occurs in week 2.
These form the fetal placenta and chorion
When do you switch nutrition sources from uterine gland secretions to uteroplacental circulation?
Uterine gland secretion provide nourishment before implantation and the completion of implantation is marked by the establishment of vascular lacunae (when uteroplacental circulation is established.)
Cytotrophoblast. What does it come from and what is its function?
Derived from the trophoblast, and arises after implantation. Its function is cellular proliferation, which gives rise to the syncitiotrophoblast. the cytotrophoblast has definitine cell membranes.
Syncitiotrophoblast. What is it derived from and what is its function? Also, what does it secrete?!
Derived from the trophoblast, formed from the cytotrophoblast to complete implantation. Cells migrate and form a syncitium, erode the uterine wall and blood vessels. These are a whole bunch of cells that work as one big cell mass. The cell membranes are missing, so that we an get nutrients (“trophs”) from mother’s circulation to embryo. It secrete human Chorionic Gonadotropic (hCG). This is what pregnancy tests detect, and can be detected at day 8.
vasular lacunae
“pools” or vascular “lagoons” of maternal blood in the syncitiotrophoblast that marks the completion of implantation during week 2.
What is being detected in a pregnancy test and what secretes it?
hCG, secreted by the syncitiotrophoblast. (at day 8)
What is the earliest you can detect a pregnancy?
day 8! (enough hCG is being secreted by the syncitiotrophoblast.
Molar pregnancy (hytadiform mole)
Trophoblast implants, but embryoblast is absent/incomplete. May produce a tumor called a hytadiform mole. hCG still secreted = positive pregnancy test.
When is the blastocyst cavity formed? When? Then, what cavity does it become? When?
Blastocyst cavity formed during cavitation after day 4. The blastocyst cavity becomes the primary yolk sac when the hypoblast devide/migrate to lines the blastocyst cavity.
What is formed when the epiblast undergoes cavitation?
Amniotic cavity is formed (during week 2 of the bilaminar disc formation.
exocoelomic membrane
The membrane of hypoblast cells that is the lining of the primary yolk sac.
primary yolk sac
formed by the lining of the blastocyst cavity by the hypoblast cells, which is now considered as the exocoelomic membrane. (week 2)
chorion
cytotrophoblast + syncitiotrophoblast + extraembryonic mesoderm
extraembryonic mesoderm
forms adjacent to the hypoblast
- spaces appear in the EM, unite to form a single large extraembryonic cavity (EC)
- part of pYS is “pinched off” to form the sYS.
How does the pYS become the sYC?
The extraembryonic mesoderm (EM) forms adjacent to the extracoelemic membrane. Then spaces in the EM appear, which unite to form a single, large extraembryonic cavity (EC). It also “pinches off” part of the pYS to for the sYS.
How is the Chorionic cavity formed?
The extraembryonic mesoderm (EM) forms adjacent to the extracoelemic membrane. Then spaces in the EM appear, which unite to form a single, large extraembryonic cavity (EC), AKA Chorionic Cavity (CC). It also “pinches off” part of the pYS to for the sYS.
What membrane makes the pYS?
Hypoblast cells that have lined the blastocyst cavity. Once this has happened the hypoblast cells can also be called exocoelomic membrane.
What might have happened if a female thought she had a period, which in reality she actually got pregnant?
When the blastocyst implants into the endometrium, implantation membrane bleeding may have occurred, which is about the time when the female would have her period.
What events occur during week 3?
1) Gastrulation: formation of the trilaminar disc (the three germ layers)
2) Neurolation: formation of the neural tube.
3) Body folding: embryonic disc folds into more complex shapes.
Note: These events begin in week 3, but they complete during week 4.
Embryonic Period
Germ layers and organogenesis, from week 3 to the end of week 8. This is the time in which it is most susceptible to teratogenesis.
Gastrulation
epiblast cells proliferate and migrate to form 3 germ layers (ectoderm, mesoderm, endoderm)
note: hypoblast cells do not contribute to the germ layers.
What cells displace the hypoblast cells?
Migrating epiblast cells that form the inner layer and become the endoderm.
Where is the site of epiblast invagination?
Primitive node and primitive streak
Primitive node and primitive streak
-site of epiblast invagination
-organize the germ layers
-determine the body axes
The primitive node is the primary migration organizer.
cloacal membrane
membrane at the tail end (caudal) of the developing embryo, which becomes the future anus.
oropharyngeal membrane
membrane at the head end (cephalic) of the developing embryo, which becomes the future mouth.
Which way are migration routes of the mesenchyme?
migration routes are caudal-to-cephalic, while development is cephalic-to-caudal.
Which way is development of embryo occurring?
Epiblast cells break free and become migrating mesenchymal cells the invagination of the ectoderm (primitive node and streak) and they migrate from caudal-to-cephalic, so near the tail end is the newer cells, while to top end will have the older, more developed cells, therefore development is cephalic-to-caudal :)
-tissue proliferation (least mature) –> tissue differentiation (more mature).
Epithelial-mesenchymal transformation
formation of undifferentiated migratory cells (mesenchymal cells)
What are the key concepts of gastrulation?
1) ALL 3 layers derived from epiblasts
2) Establishes body axes
3) Cephalic-to-caudal order of development.
What establishes the body axes, and what are the body axes?
Primitive node and primitive streak establish the body axes, which are:
1) Cephalocaudal: head-tail
2) Ventral-Dorsal: front-back
3) Medial-lateral: midline-right/left
Nuerolation
formation of nueral tube (contributes to the nervous system development) Requires notochord formation: -invaginates at primitive node/pit -migrates along midline -stops at prechordal plate
Notochord formation
-invaginates at primitive node/pit
-migrates along midline
-stops at prechordal plate
(induces nuerolation)
What induces overlying surface ectorderm to become nueroectoderm?
notochord
What happens if the rostral neuropore fails to close?
Anencephaly (“an” = with out, “cephaly” = head)
Anencaphaly
Anencephaly (“an” = with out, “cephaly” = head)
-this occurs when rostral nueropore fails to close properly.
What happens if the caudal neuropore fails to close properly?
Spin bifida and spina bifida cystica
Spina bifida
happens with the caudal (tail) neuropore fails to close properly.
What is derived from the endoderm?
Gametes
Epithelial cells lining:
-GI tract and assoc. structures (liver/pancreas)
-respiratory airways (outgrowth of GI tract)
-some urogenital structures
What is derived from ectoderm?
surface ectoderm: epidermis & its derivatives (hair, nails, glands)
neuroectoderm: nervous system and nueral crest derivatives
- formation induced by notochord
What three layers does the mesoderm differentiate to?
1) paraxial mesoderm (closest to the axes)
2) Intermediate mesoderm (in the middle)
3) lateral plate mesoderm
- parietal layer
- visceral layer
mesenchyme
Fluid rich ECM? with multipotent mesenchymal cells; undifferentiated mesodermal cells
somites
derived from the paraxial mesoderm
-their development is cephalic-to-caudal
gives rise to sclerotome, myotome, dermatome
What is derived from paraxial mesoderm?
dermis, skeletal muscle, axial skeleton
What is derived from the intermediate mesoderm?
majority of the urinary and reproductive systems
What is derived from the lateral plate mesoderm?
parietal layer: Connective tissue of body walls and limbs
visceral layer: CT of GI/respiratory organs (except the epithelial lining.
What drives lateral body folding? What does this body folding form?
driven by the lateral growth of the somites.
forms gut tube (from sYS endoderm) and intraembryonic body cavity.
What process forms the intraembryonic cavity?
Lateral body folding ,driven by the lateral growth of the somites.
forms gut tube (from sYS endoderm) and intraembryonic body cavity.
What process creates the gut tube?
Lateral body folding, driven by the lateral growth of the somites.
forms gut tube (from sYS endoderm) and intraembryonic body cavity.
What drives cephalocaudal body folding?
Driven my the longitudinal growth of the neural tube. Moves the primitive mouth and heart to adult position.
What has happened from week 4 to week 8?
End of the embryonic period
Gastrulation, nueralation and body folding complete
limbs elongate & rotate, digits appear; face develops
organogenesis: organ formation
GREATEST RISK OF BIRTH DEFECTS
What three cell types does the epiblast become?
ectoderm, mesoderm, endoderm
What type of cells does the hyopblast become?
Doesn’t become anything! It gets on the third week during gastrulation. The epiblast begins to invaginate, and epithelial like cells of the epiblast become mesenchymal cells (undeferentiated migratory cells). The invagination causes the formation of the the primitive node and primitive streak. The mesenchymal cells migrate to form the mesoderm and endoderm. The endoderm displaces the hypoblast.
What does the ectoderm develop into?
Surface ectoderm and neuroectoderm. These later develop into the epidermis and nervous system, respectively.
What does the mesoderm develop into?
Paraxial, intermediate and lateral plate (parietal & visceral) mesoderms.
What does the endoderm develop into?
Epithelium of GI & respiratory system
What does the paraxial mesoderm develop into?
Somites–>
Sclerotome dermatome myotome
Skeleton Dermis Skeletal muscle
What does the intermediate mesoderm develop into?
Urinary and reproductive systems
What does the visceral mesoderm develop into?
GI & respiratory organs (except epithelium)
What does the parietal mesoderm develop into?
Connective tissue of body walls and limbs.
Where is the sclerotome derived and what does it develop into?
Derived from paraxial mesoderm (somites) and develops into axial skeleton
Where is the dermatome derived and what does it develop into?
Derived from paraxial mesoderm (somites) and develops into dermis
Where is the myotome derived and what does it develop into?
Derived from paraxial mesoderm (somites) and develops into skeletal muscle
What stage do teratogens have the most effect?
Embryonic period
What is the period that is least susceptible to birth defects?
Fetal period
What is the fetal period’s main characteristic?
Growth and proportion
When is the greatest length gain?
months 3-5 (around between the 2nd and 3rd trimester) 600% crown-rump length (CRL increase)
When is the greatest gain in weight?
months 8-9 (3rd Trimester. (30,000% weight increase.
Biparietal diameter
measurement (from each parietal lobe) used for managin pregnancy (birth defects, fetus/birth canal size ratio)
What measurements are used when managing pregnancy?
- Crown-Rump Length (CRL)
- biparietal diameter
- abdominal circumference
- femur length
What are some important occurrences during the fetal period?
Week 10: Swallowing, urine formation Week 12: Bone ossification, external genitalia visible with ultrasonography. Week 15: Respiratory movements weeks 24-28: sound and light recognition 5th month: fetal movements
What fluid does the fetus swallow?
amniotic fluid
If the fetus’s movement is restricted, what may happen?
Movement is important for joint develop.
Lanuga
downy hair, which holds vernix in place
Vernix caseosa
secreted from the skin. greasy, protection, insulates it a little bit, lubrication, also antibactorial properties.
What is the last major organs to develop?
Lungs (not fully developed until after birth. bringing in air into lungs after birth completes development of lungs.)
When is the risk for RDS the highest?
Respiratory distress syndrome. . .
- high <28wk
- moderate 28-34wk
- low 34wk
What test can be done to detect RDS?
Lecithin-sphingomyelin ratio (substances in the amniotic fluid)
What is the treatment for RDS?
Treated with steroids prenatally and continuous positive airway pressure (CPAP) postnatally.
What keeps alvioli to collapse? what happens if baby is born before it?
surfactant
Respiratory distress syndrome
Is postmature or premature correlated with morality?
Both! postmature has problems like the placenta deteriorating, and also the baby being too large for the female.
What is it called when the weight of the fetus is too small? What does that cause?
Small for gestational age (SGA)
In utero growth retardation (IUGR)
What is in utero growth retardation (IUGR) and what are the effects? long and short term
IUGR happens when the fetus is Small for Gestational Age (SGA).
IUGR effects: neurological problems, RDS, hypoglycemia, hypoalcaemia
IUGR long term effects: metabolic disorder, poor health in general
What is the normal presentation of baby during birth?
Normal: Head-first presentation
What is it called when a baby does not present normally during birth? What are the variations?
Breech: buttock or feet-first penetration
complete breech: indian style
incomplete breech: indian style with one leg up
frank breech: straight ass out, legs up
-typically delivered by C-section
What are the different types of fetal monitoring?
Ultrasonography (ultrasound, sonogram) Amniocentesis Chorionic Villus Sampling (CVS) Maternal serum screening Fetoscopy Percutaneous Umbilical Cord Blood Sampling (PUBS)
What tests are used to visualize the fetus?
Ultrasonography (ultrasound, sonogram) and fetoscopy
What tests are used to collect genetic material and fetal markers?
amniocentesis, chorionic villus sampling (CVS), maternal serum screening, Percutaneous umbilical cord blood sampling (PUBS)
What test is preferred after the 5th week?
Ultrasonography
Ultrasonography (ultrasound, sonogram)
sound pressure waves to visualize fetus.
>5 weeks (large enough to see)
Most common type of fetal monitoring, no known side effects, inexpensive
Monitors growth (CRL BPD etc.), sex, morphology, circulation
What test can be done at week 10-14?
Chorionic Villus Sampling (CVS) (after 14 weeks, amniocentesis is preferred)
Chorionic Villus Sampling (CVS)
Biopsy of chorionic villus w/ needle guided by ultrasonography. 10-14 weeks (after 14 wks amniocentesis is preferred) Risk of complications = 1-2%. Slightly higher risk than amniocentesis. Less accurate than amniocentesis (chromosomal abnormalities in cells. Although it has earlier karyotyping.
Amniocentesis
sampling fluid w/ needle guided by ultrasonography. Done around 14-20 weeks (adequate fluid). Low risk (<1% complications)
Fetal cells: karyotyping
Fetal metabolites, proteins, hormones, etc.
also, lectin-sphingomyelin test for surfactant
Maternal serum screening
identifying fetal markers in maternal blood (timing is marker-specific
Alpha-fetoprotein: nueral tube defects, GI defects, Down syndrome
-hCG: molar pregnancy, down syndrome.
numerous false positives.
What is Percutaneous Umbilical Cord Blood Sampling (PUBS)? When is it used? What are the risks?
Sampling of umbilical vein blood for genetic or metabolic disorders (also: cordocentesis)
>17 weeks (cord large enough)
Same risk as CVS (1-2%)
During a molar pregnancy, what cells are malfunctioning?
Embryoblast isn’t functioning correctly or missing, so the cytotrophoblast is doing its job to proliferate into synciotrophoblast, but there is incorrect or no communication with embryo.
What are the key concepts in the molecular basis of development?
1) Genes that guide development are highly conserved (few genes, many effects)
2) Timing of gene expression is cell-specific and location-specific (when and where genes are expressed determines when and where structures develop)
3) Molecules involved: signaling molecules and txn factors ACT ON: developmental geness
What is the molecular basis of dorsalization?
BMP4 from ectoderm promotes expression of Pax 3 & Pax 7
What is the molecular basis of ventrilization?
Shh from the notochord antagonizes BMP4 (repressors Pad3/7) - induces neuroectoderm (neural crest and neural tube) formation
When does the oropharyngeal membrane appear and what will it become?
Week 3 (during gastrulation). It will become the future mouth.
When does the cloacal membrane appear and what will it become?
Week 3 (during gastrulation) It will become the future asshole.
How does the notochord form, what does it induce, and what is the molecular basis the induction?
It invaginates at primitive node/pit, migrates along midline, stops at prechordal plate. Notochord induces neurolation. Notochord secretes Shh, which turns on Pax genes, which turns on Pax proteins, which induces the the neural crest/tube formation, as well as motor neuron cell fate (once the tube is formed).
What is the prechordal plate?
It is where the notochord stops at.
Put these in chronological order:
neural tube, neural folds, neural groove
It goes in alphabetical order
Folds, Groove, Tube
Where do gametes originate from?
Endoderm
What does intermediate BMP4 and Shh induce, and where are each of these being secreted from?
neural crest. BMP4 from ectoderm, Shh from notochord.
What does low BMP4 and high Shh induce?
neural tube
What induces sensory neuron fate?
BMP4 from surface ectoderm and roof plate induces sensory neuron plate.
What induces motor neuron fate?
Shh from notochord and floor plate induces motor neuron fate.
What does snail do?
specifies neural crest cell fate
What does slug do?
promotes cell migration (around neural crest)
What does high BMP4 and low Shh induce?
surface ectorderm
What does high BMP4 induce?
Lateral plate mesoderm
What does intermediate BMP4 induce?
intermediate mesoderm
What does low BMP4 induce?
paraxial mesoderm
What genes are responsible for craniocaudal body segmentation?
“homeobox” family of genes. These code for txn factors called hox proteins. (4 chromosomes and 13 gene clusters) (Hox A chromosome and gene cluster are at the caudal end, so that is developed first)
What genes are responsible for spatial/temporal collinearity og gene expression and development?
“homeobox” family of genes. These code for txn factors called hox proteins. (4 chromosomes and 13 gene clusters) (Hox A chromosome and gene cluster are at the caudal end, so that is developed first)
What signaling molecules make up the differentiation front? Which sides are these molecules coming from?
RA from the caudal (rostral)(more developed) end and FGF8 from the cephalic (less developed) end.
Where is the differentiation front?
It is at the developing somites (where RA signal overpowers FGF8 signal)
What molecules/gene/txn factor induces dermatome formation?
signaling molecule secreted by neural tube, NT-3 turns on Pax genes for txn Pax 3.
What molecules/gene/txn factor induces sclerotome formation?
Signaling molecule from notochord, Shh, turns on Pax genes for txn factor Pax 1. paraxial mesoderm to become sclerotome.
What is the molecular basis for the induction of myotome?
Signaling molecule: Wnt
Developmental gene: MRF
Txn factor: Myf5 and MyoD
secreted by: neural tube and surface ectoderm
What does FGF8 do in order to develop left-right asymmetry?
FGF8 affects cilia development in the primitive node - forms left-sweeping cilia. This sweeps Nodal from the primitive node to the left side of the embryo, which induces lateral plate mesoderm to form left-side structures by promoting expression of Pitx2 txn factor.
Signaling molecule RA/FGF8
Developmental gene: Hox Genes
Txn Factor: Hox proteins
Secreted by: RA: Caudal mesoderm, FGF8 cranial mesoderm
Structure Induced: somites
Signaling molecule BMP4/Shh
Developmental gene: Pax genes
Txn Factor: Pax proteins (3 & 7 for surface ectoderm)
Secreted by: BMP4 from ectoderm and Shh from notochord
Structure Induced: surface ectoderm, neural crest/tube, motor/sensory
Signaling molecule BMP4
Secreted by: lateral plate mesoderm Structure Induced: paraxial mesoderm = low [BMP4] intermediate mesoderm = intermediate [BMP4] lateral plate = high [BMP4]
Signaling molecule Shh
Developmental gene: Pax Genes
Txn Factor: Pax 1
Secreted by: Notochord
Structure Induced: sclerotome
Signaling molecule Wnt
Developmental gene: MRF
Txn Factor: Myf5 and MyoD
Secreted by: neural tube and surface ectoderm
Structure Induced: myotome
Signaling molecule NT-3
Developmental gene: Pax genes
Txn Factor: Pax 3
Secreted by: neural tube
Structure Induced: dermatome
signaling molecule Nodal
Txn Factor: Pixt2
Secreted by: primitive node
Structure Induced: left-right asymmetry
Birth Weight Ranges
3200g = normal <500 = fatal
What is the risk of RDS during what timeframes? What test can be done? How do you treat it?
Risk:
-high= 34wk
Test: Lecithin-sphingomyelin ratio: substances in the amniotic fluid.
Treated with steroids prenatally and continuous positive airway pressure (CPAP) postnatally
During week 2, what are the cells lining the newly formed amniotic cavity?
amnioblast
What comprises the amniochorionic membrane?
formed by the fusion of amnion and chorion (cytotrophoblast, syncitiotrophoblast and extraembryonic mesoderm). This is the membrane that breaks (AKA “water breaks”)
What do the vascular lacunae become?
intervillus spaces
Amniotic Band Syndrome (ABS)
Premature rupturing of ACM
bands/cord of ACM constrict fetal body parts
may affect development of more distal structures
Amniotic fluid
circulating clear, watery liquid
formed by: amniotic cells lining the cavity and diffusion of maternal tissue fluid
Enters fetal circulation: swallowed in GI tract, aspirated into lungs, absorbed through skin.
Returns to maternal circulation: uteroplacental circulation, excretion into amniotic cavity and diffusion into maternal tissue.
Contains fetal cells, proteins, electrolytes (amniocentesis)
Amniotic Fluid Functions:
Cushions, prevents adhesion, permits movment (aids muscular & respiration development), permits growth, barrier to infections, regulate body temperature, regulate fluid/electrolyte homeostasis
Amniotic Fluid Volume
~1000ml in 3rd trimester
polyhydramnios; >1500ml
oligohydramnios; < 400ml
Polyhydramnios
Too much amniotic fluid; > 1500ml
idiopathic (unknown cause) or associated w/ severe malformations that prevent swallowing of amniotic fluid.
Oligohohydramnios
Too little amniotic fliuid; <400 ml
- renal agenesis, urinary blockages, premature rupture of ACM (PROM)
- may lead to slowed growth or oligohydramnios secquence.
Oligohydramnios sequence
Abnormal appearance due to compression of fetus against uterus (limb abnormalities, flattened face)
Typically caused by bilateral renal agenesis or ACM rupture.
Characterized by oligoyhydramnios, anuria (no urination), pulmonary hypoplasia.
Umbilical cord
attaches fetus to placenta
contains: -1 umbilical vein, blood: placenta to fetus
- 2 umbilical arteries, blood: fetus to placenta
- loops of intestines, yolk sac, vitelline vessels
- allantois (collects waste)
How many umbilical veins are there and does it carry oxygenated or deoxygenated blood
1 umbilical vein. Blood is moving towards fetus from the placenta and it is carrying oxygenated blood.
How many umbilical arteries are there and does it oxygenated or deoxygenated blood
2 umbilical arteries. blood is moving AWAY from the fetus. this carries deoxygenated blood.
What is the healthy dimensions of an umbilical cord? What could happen if it too short or too long?
~55cm, 1-2 cm diameter
Long cord: prolapse, nuchal cord (encircles fetal neck)
Short cord: restricted fetal movements, early detachment of placenta from uterus during delivery
Umbilical cord loops and knots
True knot: fetal hypoxia/anoxia (little/no oxygen); may be fatal
False knot: kinks/loops in the cord; no clinical significance
umbilical cord blood banking
collection, storage of fetal blood cells (derived from umbilical cord blood)
Alternative to bone marrow transplants
Benefits: no discomfort during collection, abundant viable stem cells, minimizes host-graft rejection.
Issues: long-term viability not guaranteed, low probability of use, expensive
Placenta
site of nutrient and gas exchange between fetus and mother. produces pregnancy hormones like hCG. Comprised of the basidua basalis (maternal, from endometrium) and villous chorion (fetal, from chorion)
Decidua
name for endometrium during pregnancy (decidual reaction during pregnancy)
decidua basalis: maternal placenta adjacent to fetal placenta
decidua capsularis: overlies non-placental portion of the conceptus.
decidua parietalis: endometrium not directly associated with concetpus
Decidua capsularis
the non-placental overly of maternal endometrium (decidua) around the conceptus
decidua basalis
maternal placenta adjacent to fetal placenta
decidua parietalis
endometrium not directly associated with conceptus
Chorion
name for extraembryonic mesoderm + trophoblast layers. Villous chorion: fetal placenta adjacent to the decidua basalis. smooth chorion: less vascular, smoother, non-placental region
Villous chorion
EM + trophoblast layers that is part of the fetal placenta, adjacent to decidua basalis.
Develops as the cytotropoblast and extraembryonic mesoderm grow into the syncitiotrophoblast.
Nutrition/oxygen flow before 4 months of age
spiral arteries in endometrium -> intervilious spaces -> syncitiotrophoblast -> cytotrophoblast -> EM -> endothelial cells lining capillaries in extraembryonic medoderm -> umbilical vein -> fetus
Nutrition/oxygen flow after 4 months of age
spiral arteries in endometrium -> intervilious spaces -> syncitiotrophoblast -> endothelial cells lining capillaries -> umbilical vein -> fetus
4 before 4 months, 2 after 4 months. take out the middle two.
Placental barrier before 4 months fertilization age
1) syncitioblast
2) cytotrophoblast
3) Extraembryonic Mesoderm
4) endothelial cells lining capillaries
Placental barrier after 4 months fertilization age
1) syncitioblast
2) endothelial cells lining capillaries
(cytotrophoblast cells detach and migrate to line maternal spiral arteries)
What does the placental barrier allow through and what does it block?
not a true barrier, often called the “placental membrane”.
Blocks: large, complex molecules, most protein hormones, most bacteria
Allows: gas, nutrient. waste exchange, steroid hormones, some antibodies, most medications/drugs (including alcohol, many viruses
Preeclampsia
clinical concern > 4 months
caused by immune reaction or failed migration of cytotrophoblast cells. increases pressure in maternal vessels
results: maternal hypertension, proteinuria
slowed fetal growth
potential death of fetus and/or mother
(Eclampsia follows preeclampsia and is characterized by seizures.
Eclampsia
clinical concern > 4 months
caused by immune reaction or failed migration of cytotrophoblast cells. increases pressure in maternal vessels
results: maternal hypertension, proteinuria
slowed fetal growth
potential death of fetus and/or mother
(Eclampsia follows preeclampsia and is characterized by seizures.
Placenta accreta
placenta Attaches to the myometrium of uterus
Placenta increta
Placenta Invades myometrium of uterus
Placenta Percreta
Placenta penetrates the uterus and extends into body cavity
Fetal circulation
Cardinal veins: body -> heart
aortic system: heart -> body
vitelline system: to & from yolk sac
Dizygotic twins
All DZ twins are dichorionic, diamniotic
(2 amnions, 2 chorions, 2 placentas
2 oocytes released at ovulation & fertilized separately. unique DNA, “fraternal”
2 blastocysts, each implant separately in endometrium. (Close implantation may result in fused placentas & chorions, but still DCDA twins)
MZ Twins; dichorionic, diamniotic (DCDA, DiDi)
-2 amnions, 2 chorioins, 2 placentas
1 oocyte released at ovulation, fertilized by 1 sperm. same DNA, “identical”
splitting prior to implantation: each blastocyst implants separately in endometrium.
MZ Twins; monochorionic, diamniotic (MCDA, MoDi)
2 amnions, 1 chorion, 1 placenta
1 oocyte released at ovulation, fertilized by 1 sperm; same DNA, “identical”
Splitting of inner cell mass prior to implantation
-2 embryoblasts before implantation = 2 amnions
-1 trophoblast = 1 chorion and 1 placenta
MZ Twins; monochorionic monoamniotic (MCMA, MoMo)
1 amnion, 1 chorion, 1 placenta
1 oocyte released at ovulation, fertilized by 1 sperm; same DNA, “identical”
Splitting of inner cell mass after implantation
-1 embryoblast at implantation = 1 amnion
-2 epiblast after implantation = 2 fetuses
-1 trophoblast = 1 chorion and 1 placenta
Conjoined twins
incomplete splitting on monozygotic twins
parasitic twins
asymmetrical conjoined monozygotic twins
vanishing twin
death of 1 fetus (~70 % of twins)
twin transfusion sydrome
unbalanced blood flow to monochorionic twins
