Embryology Part 3/ Reproductive Endocrinology Flashcards
What two hormones are important in neural tube development?
Chordin and Noggin
Presence inactivates BMPs and particularly BMP4 (meaning patterning of neural tube and somites can occur, as if BMP 4 was present this would be inhibited).
What is the neural groove?
The depression formed within the ectoderm when the lateral edges of the plate fold inwards.
This groove forms the neural tube
What germ layer forms the neural tube and which forms the notochord?
Neural tube- Ectoderm (although mesoderm influences the thickening of ectoderm to become neuroectoderm)
Notochord- Mesoderm
What mechanical forces help control the bending of the neural plate?
Cell Wedging- microtubules and microfilaments changing cell shape, cell cycle Hinge Points (most important)- median and dorsolateral hinge points Extrinsic forces- Pushing of the surface ectoderm, adhesion point with notochord.
What are neural crest cells?
Highly migratory cells forming at time of neurulation
Give rise to craniofacial structures, teeth, melanocytes, dorsal root ganglia
When does neural tube closure occur, in days?
Week 4 (anterior by day 25, posterior by day 27)
Briefly describe the process of neural tube closure
Noggin inhibits BMP which allows for hinge point formation (dorsolateral and median hinge points). Cell wedging and extrinsic factors also aid in neural bending.
Fusion begins at cervical region and moves in cephalic/caudal directions
Open ends form anterior and posterior neuropores (connect to overlying amniotic cavity)
Closure occurs at week 4
What is a neural tube defect, and when do they occur?
Result of failure or incomplete closure of the neural tube
Occurs during week 4
What are the two types of neural tube defects, what do they typically cause, and where along vertebrae do they most commonly occur?
Failure at anterior neuropore- anencephaly
Failure at posterior neuropore- spina bifida
Most common at lumbosacral region
What factors increase risk of developing neural tube defects?
Not enough folate
Certain medication (anti-epileptics)
Ethnic Background (Celtic origin)
Genetics (unusual sonic hedgehog signalling, 1 child with spina already)
What determines the severity of spina bifida?
Severity depends on where the failure to close occurs, but all result in a loss of neural functioning
Give examples of different types of spina bifida.
Occulta (hidden) is least severe- hidden, typically only found when vertebral scanning is done (or tufts of hair seen)
Meningocele - Sac protruding containing meninges and spinal fluid, but not neural tissue
Myelomeningocele- spinal cord protrudes through the opening. Can result in paralysis and nerve damage
How is spina bifida diagnosed?
Ultrasound at 20 weeks
Raised alpha-feto protein can indicate higher risk, but not diagnostic
How is spina bifida prevented?
Folate prior to and during first 12 weeks of pregnancy
Its a co-factor enzyme involved in DNA/RNA biosynthesis (lack of it can impact cell proliferation)
Folic acid is the oxidized, most active form
What anti-epileptic drug poses a 4 in 10 chance of developmental disorders, and 1 in 10 chance of birth defects?
Valproate
Lamotrigine and Levetiracetam are the safest options for pregnancy
Why is Sonic Hedgehog so important, how does its release start, and how does it influence nearby structures?
It is the closest to a master genes
Helps with patterning of neural tube, and somite patterning (sclerotome formation)
Notochord sends out sonic hedgehog, and it passes to developing neural tube, ventral area of tube is the responder, and its response is differentiation into the floor plate of the neural tube.
Once floor plate is differentiated, it can produce SHH, which causes nearby cells to form motor neurons.
How is sonic hedgehog potentially related to spina bifida?
Increased expression of sonic hedgehog in lower neural tube prevents the formation of the dorsolateral hinges, preventing closure of the tube.
This is because SHH inhibits noggin, and noggin works to inhibit BMP, and BMP (particularly BMP 4) is what prevents hinge point formation.
So with SHH in cephalic end increasing, more BMP is left un-inhibited, meaning it can prevent the dorsolateral hinge points from forming, which means the neural tube cant close (spina bifida).
This isn’t as much of a problem at the caudal end as cervical vertebrae don’t need the dorsolateral hinge points to close.
What are the four manifestations of abnormal development?
Death, malformation, growth retardation, and functional deficit
What factors influence teratogenesis?
Genotype of conceptus
Developmental stage at time of exposure
Dosage
What is a teratogen?
An “agent that can disturb the development of an embryo or foetus”. Teratogens can come in many forms, exposure to teratogens during pregnancy can have a range of effects ranging from very mild to severe, or causing death of the embryo/foetus.
What are the 5 types of teratogens?
Drugs and chemicals Industrial pollutants Hormones Infectious Agents Mechanical Factors
What is thalidimide? What are the critical time points impacted by the drug, and what will it impact?
An anti morning-sickness drug for pregnant women
Caused blood vessels in early progress zone of limbs buds to leak, resulting in complete absence (amelia) or partial absence (meromelia) of limbs
Days after conception Affected system
21-22 Ears, cranial nerves
24-27 Upper limbs
27-35 Lower limbs
34-36 Thumbs, rectum
What are examples of antibiotics that are teratogens? Give a very brief explanation of their impact.
Tetracyclines- cross placenta and deposit at sites of calcification in bones and teeth, impacts enamel formation and colour.
Streptomycin- Can cause inner ear defects.
What painkillers are thought to be teratogens, and what may they be impacting?
Paracetamol- male reproductive development
Ibuprofen- first trimester, reduction in germ line numbers of future children/grandchildren
Aspirin- heart defects
What are examples of prescribed drugs that act as teratogens?
Anti-epileptic drugs (particularly valproate)- folate inhibitor
Methotrexate- used in lupus, rheumatoid arthritis, psoriasis- works as folate inhibitor
Antineoplastic drugs- designed to kill rapidly dividing cells
Vitamin A for acne- Deformities for structures derived from neural crest cells
Warfarin- issues with bone development
What hormones can act as teratogens? Briefly touch on what they impact
Androgens- masculinization of female genitalia Endocrine disruptors (synthetic oestrogens from the environment)- increased vaginal/cervical carcinoma incidence, testis malformations and abnormal sperm
What are the characteristics of foetal alcohol syndrome?
Facial deformities Low birth weight small head circumference Developmental delay Memory problems Behavioural problems Poor motor skills Difficulty socializing
What is the mechanism behind how alcohol impacts a fetus?
Alcohol easily crosses placenta
Alcohol cannot be metabolized by foetal liver, resulting in high blood alcohol levels
Alcohol impairs white matter development and reduces oxygen and nutrient levels
How does radiation work as a teratogen?
Radiation kills rapidly dividing cells
Highly fatal and causes severe birth defects
How do cigarettes work as a teratogen?
Intrauterine growth retardation
In terms of the pre-embryonic stage of development, what sort of impact will teratogens have?
Weeks 1-2
All or nothing impact typically, will either cause spontaneous abortion, or no effect at all (as the regulative development can make up for the 1 or 2 cells impacted/killed)
Thought to cause 50% of miscarriages
In terms of the embryonic stage of development, what sort of impact will teratogens have? State the weeks of this stage
Weeks 3-8
Organogenesis is occurring
Teratogens have very high impact on developing foetus
Malformations (i.e. heart defects) are most common
Type of defect seen depends on which organ system is developing at the time of exposure
In terms of the foetal stage of development, what sort of impact will teratogens have? State the weeks of this stage
Weeks 9-38
Susceptibility to teratogens are reduced
Mostly functional defects occurring
Urogenital and nervous system are still vulnerable
What germ layer(s) form the amnion?
Somatic mesoderm and ectoderm
What germ layer(s) form the umbilical vein?
Somatic mesoderm and ectoderm
What germ layer(s) form the yolk sac?
Lined with the endoderm (from the hypoblast) and splanchnic mesoderm
Describe the process of extra-embryonic haematopoiesis and what component is responsible for it.
The yolk sac
Produces blood from weeks 4-6 until foetal liver is produced
Yolk sac also helps with GI development
When does the yolk sac disappear?
18 weeks
What is the chorion? Include germ layer derivatives.
Foetal part of the placenta
Combines with maternal side of placenta to form complete placenta
Its a layer of trophoblast (cytotrophoblast), plus a layer of extraembryonic mesoderm that sits outside of the amnion
What is the allantois? Include germ layer derivatives.
Foetal membrane laying below chorion
Some vasculature that gets incorporated into umbilical chord
Derived from the yolk sac which comes from the endoderm (hypoblast) and splanchnic mesoderm
What is the decidua reaction?
Progesterone causes stromal cells of uterus to enlarge and accumulate glycogen
Invading cells of blastocyst erode endometrium allowing for it to burrow into endometrium for implantation
Endometrial vessels become dilated around implantation
Where does they decidua come from?
Come from endometrium
