Teratology 1 Flashcards
Teratology
The study of the causes, mechanisms and manifestations of developmental deviations of either structural or functional nature
Causes of malformations
25%= genetic or chromocomal factors
10%= known environmental factors
65% =unknown
Teratogen susceptibility principles
- depends on genotype of conceptus and the manner in which conceptus interacts with adverse environmental factors
*few teratogens - Varies with developmental stage at the time of exposure to an adverse influence
most important
Teratogens - environment or genetic
Few teratogens that are 100% genetic or 100% environmental
Ex. cortisol in mice causes cleft palate but not in rates… therefore just a genetic component
Developmental stages in which exposure occurs
- predifferentiation
- early differentiation
- advanced organogenesis
Susceptibility graph
Appearance/development of smooth ER
-major species differences
-SER is what metabolized the teratogen… so if it occurs right near birth than more resistance because fetus is well developed
Manifestations of abnormal development
- Abortion/Death (likely 1st trimester, but can be any)
- Sub-lethal repair
-damage that is repaired - Malformations (eg. heart defect; 1st trimester)
4.Reduced growth retardation (eg. nutrient deprived in last trimester therefore smaller)
- Postnatal functional deficiency
Teratogens and carcinogens
Teratogens and carcinogens should cancel each other out if they are working on the same cells
How do teratogenic agents impact developing cells and tissues?
They will undergo a specific mechanism (eg. mutation, altered DNA, enzyme inhibition etc.) on the cells or tissues, causing pathogenesis of a common pathway leading to a defect
Mutations
-acids, x-rays, alkylating agents
Chromosomal abnormality
Not hereditary. Occurs during mitosis or meiosis. Causes: x rays, chemicals, viruses
Mitotic interference
Anything altering mitosis (rapidly dividing cells)
-chemicals, drugs, x rays,
Lack of precursors or substrates
Fetus is metabolically active so lacking precursors or substrates can affect this metabolism and development
eg. antibiotics, vitamin and mineral deficiency, failure of absorption preventing access to nutrients (Cu, Zn, sulfates, etc)
Reduced energy sources
-chemicals, drugs impacting the metabolic processes (ETC, glycolysis etc.)
eg. cyanide affects ETC
Enzyme inhibition
Any enzymes needed for DNA or protein synthesis and repair
eg. Zn needed for enzymes and can result in inhibition without it
Osmolar imbalances
-Edema between ectoderm and mesoderm preventing proper interaction and development
*not common in vet med
Altered membranes
Vit A (too much or too little)= defects
Causes of abnormal embryogenesis
- excessive cell death
- failure of cell interaction
- mechanical disruption
- reduced biosynthesis
- impaired morphogenic movement
- altered differentiation schedules
Excessive cell death
-eg. cats with multiple digits because excess cell death occurring at areas other than between normal 5 digits
Reduced biosynthesis
-mineral and vit deficiencies
Impaired morphogenic movement
-common in palate and urogenital tracts
-cell-cell, nutrient-nutrient interactions needed to occur at same time and form correctly
Sites of teratogenesis
- Fetus (direct)
- Fetal-placental unit
- Mother (altered hemostasis)
- Father (sperm)
Accessibility of teratogens
-access of agent to the developing tissues depends on physical nature of agent
-size, charge of particle, protein binding (likely cannot cross)
Factors affecting fetal dose
- maternal dose
- maternal absorption rate
- maternal metabolism
- plasma half life (short half life in mother does not mean that it is not teratogenic to fetus)
- protein binding (protein bound in mother than won’t get to fetus, but if protein bound in fetus then will store there)
- placental transfer
- molecular weight (below 600g more teratogenic)
- charge (neutral drugs can cross and are more teratogenic)
Dosing zones/effects
Dose and developmental age
check this?
Types of interactions
