9 – Teratology 1 Flashcards
What is teratology?
- Study of the causes, mechanisms and manifestations of developmental deviations of either structural or functional nature
What are the % of causes of malformations? (3)
- 25% genetic or chromosomal factors
- 10% known genetic factors
- 65% unknown
Causes of abnormal development: 4 broad categories
- Genetic
- Infectious
- Nutritional
- Toxic (smallest % of abnormal development problems)
- (Physical)
What are some principles of teratology?
- Susceptibility depends on environment and genetics
- Susceptibility varies with developmental stage
- Act in specific ways on developing cells to initiate sequences of abnormal developmental events
- There are various final manifestations of abnormal development
- Access of agents to developing tissues depends on physical nature of the agent
What does the susceptibility to teratogenesis depend on?
- Genotype of conceptus and manner in which it interacts with adverse environmental factors
o Gene=intrinsic
o Environment=extrinsic (anything outside the embryo, including the mother!) - *interaction between environment and genetics
o Usually a mixture between the two
Cortisone in mice: example with susceptibility
- Cleft palates
- *does not do that in rats
- **genetic component example
Thalidomide: example with susceptibility
- Teratogenic in people but not most other species
Why are there such differences in species?
- Absorption
- Excretion
- Metabolism and biotransformation
- Placental differences
Teratogens
- Agents that interfere with abnormal or normal development
- **DESTORY CELLS
**What does susceptibility to teratogenesis vary with?
- Developmental stage at time of exposure to an adverse influence
o 1. Pre-differentiation
o 2. Early differentiation
o 3. Advanced organogenesis
1st trimester
- most important=organ development *high susceptibility
- 2nd: maturation
- 3rd: growth (neurologic, immune problems, behavioural): growth retardation
Implantation
- Usually a week
- Not particularly susceptible
Right after implantation (organogenesis)
- Fetus in active stage of growth
- ***PRIME SUSCEPTIBLIITY
o High metabolic activity - Some organ cells develop
o If agent comes in and destroys all cells=no organ - Day 30: Declines in susceptibility
Appearance of SER in liver
- Major specie differences!
- *development is usually later in pregnancy
o More susceptible as it is closer to when they are born - If have=metabolize the teratogen=REDUCES IT
o Unless it requires bioactivation=will increase it!
Teratogenic agents act in specific ways (mechanisms): ‘following steps’
- Mechanism
- Pathogenesis
- Common pathway (usually 1st trimester, but not always)
- *results in a defect
a. May vary depending on time period
b. May have a variety of teratogens that could cause it
Example of some mechanisms that teratogenic agents act
-mutation
-chromosomal abnormality
-mitotic interference
-altered DNA
-lack of precursors of substrates
-reduced/altered energy sources
-enzyme inhibition
-osmolar imbalances
-altered membranes
Mutation
o strong acids, X-rays, alkylating agents
Chromosomal abnormality(=NOT hereditary, can occur during mitosis or meiosis)
o X-rays, chemicals, viruses
Mitotic interferance
o Drugs, X-rays
- Lack of precursors or substrates
o Needs lots of nutrients, may affect protein synthesis (anti-biotics!), transcription, incorporation of base pairs
o *Vitamin deficiencies (Vit A and E), minerals (zinc, Mg): protein synthesis (get Vit A and E from colostrum!)
o Failure of absorption: Cu, Zn, sulfates (Gut or placental level)
If mom is okay then likely a placental problem (not the feed)=placental transport is a big factor!
Reduced/altered energy sources
o Cyanide=ETC
o Fluorine=Kreb’s cycle
Enzyme inhibition
o Especially those in DNA or protein synthesis and repair
o *Many enzymes contain Zn, so if animals have a Zn problem that may be the cause
Osmolar imbalances
o If edema develops between ectoderm or mesoderm=can’t interact problem
If a nutrient growth factor=abnormal development
o Not common in vet med
Altered membranes
o **Too much Vit A=will cause defects (animals AND people) (also deficiency)
Very potent
