teratology Flashcards
teratology
-the study of the causes, mechanisms and manifestations of developmental deviations of structural or functional nature.
principle 1
susceptibility to teratogenesis depends on the genotype of the conceptus in a manner in which it interacts with adverse enviro factors.
-simple: enviro factors interact with fetus to form defect
gene- intrinsic
environment-extrinsic (even the mother if sick)
teratogens
-agents with interfere with normal development
principle II
-susceptible to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence.
-stage of exposure at what stage of development matters
stages:
1 predifferentiation
2 early differentiation (most critical)
3 advanced organogenesis
manifestations of damage
-abortion (most common)
-early embryonic death
-sub lethal repair
-morph defects malformation (depends on # of cells that are destroyed)
-later pregnancy: growth retardation
-teratogens destroy cells
embryonic period
1st trimester: organ development, where you get fetal deaths and abortions, morph defects, malformations
2nd trimester: growth and maturation, less susceptibility, most susceptible
3rd trimester: less susceptibility, growth retardation, behavior effects (when nervous and immune system develops)
principle III
teratogenic agents act in a specific ways (mechanisms) on developing cells and tissues to initiate sequences of abnormal developmental events (pathogenesis)
-mechanism-> pathogenesis-> common pathway-> defect
some mechanisms: mutation, chromosomal abnormality, altered DNA
causes of abnormal embryogenesis
1 excessive cell death (underlying factor period) if they destroy enough cells can stop entire organ from forming cause absorption.
2 failure of cell interaction
3 mechanical disruption
4 reduced biosynthesis
5 impaired morph movement
6 altered differentiation schedules
sites of teratogenesis
1 fetus-direct
2 fetal-placental unit
3 mother- altered homeostasis
4 father-sperm
principle IV
the final manifestations of abnormal development are:
1 death
2 malformation
3 growth retardation
4 postnatal functional deficiency
principle V
The access of adverse influences (agents) to the developing tissues (fetus) depends upon the physical nature of the agent.
factors affecting fetal dose
1 maternal dose
2 maternal absorption rate
3 maternal metabolism
4 plasma half life
5 protein binding
6 placenta transfer
7 molecular weight (anything below 600 g is teratogenic)
8 charge (neutral toxins cross the placenta and are more teratogenic)
principle VI
-manifestations of abnormal development increase in frequency and degree with dose from the no effect level to the lethal zone.
-the teratogenic window is very small. maternal lethal zone and embryolethal zone are large.
manifestations of abnormal development are influenced by
dose
time
duration of exposure
species
genetic causes of abnormal development
-gene mutation
1 autosomal
2 sex linked: hemophilia
3 chromosomal abnormalities: chimerism
infectious causes of abnormal development
1 bluetounge virus: cattle sheep, embryonic death, resorption, arthrogyposis
2 BVD: absorption, early embryo death, placentitis, cerebellar hypoplasia
3 parvovirus: effects rapidly dividing cells in dogs and pigs.
1st trimester: reportion
2nd: abortion
3 few effects
4 feline panleukopenia virus:
death, ataxia, cerebellar hypoplasia, hydrocephalus.
nutritional deficiencies causing fetal abnormalities
vitamin A: blind, micropthalmia, abortion, stillbirth, CNS, renal malformations
vitamin E/ Se: cardiomyopathy
minerals:
copper: enzootic ataxia
selenuium
magnese: cartilage
iodine: prolonged gestation, goiter, hairless
veratrum calcification
-can cause cyclops, cleft palate, death, depends on time of exposure
-from alkaloids
-mechanism reduced cell mitosis/ migration reduced choncrocyte proliferation.
lupines (crooked calf disease)
-arthrogryposis, cleft palate, spinal curvature, torticolis, scoliosis
-agent alkaloid, anagryrine
tabacco (nicotiana)
pigs: cleft palate, arthrogyposis
-agent anabasine
chemicals causing abnormalities vitamin A toxicity
-mechanim: interfers with neural crest cell migration
lesions: fatal resorption, cleft palate, micropthamia, spina bifida, heart, gi defects, most defects in the eyes
-toxicity occurs at therapeutic doses not high doses
chemicals causing abnormalities albendazole
-mechanism: inhibits microtubule formation
-lesions: spina bifida, bone & kidney defects
chemical organophosphate insecticides
-embryotoxic, fetotoxic
-mechanism: inhibit ach neutransmitter
-lesions: death of fetus or CNS, learning impairment, behavior change
organochlorine insecticides (DDT, lidane)
-estrogenic mechanism leads to no implantation, resorption, reduced CL formation, reduced sperm
griseofulvin
not species specific
-antifungal drug
-reduced microtubule and mitotic spindle function
lesions: absorption, bone, neural tube, cyclopia, anopthalmia
cyanide (plant)
-mechanism: effects energy and oxygen utilization
-lesion: arthrogryposis, no limb movement in utero (involves limb movement or neuro= arthrogyposis)
nitrates
-plant origin
-mech: methemoglobin formation and anoxia leads to abortion in fetus, dam is fine
-in drought stress crops, herd problem, cows can adapt if you build up to high nitrates over time
mycotoxins causing abnormalities
-fungal metabolites
1 zeralenone: estrogenic
2 alfatoxin/ fimonsisns rapidly dividing cells
3 trichothecenes: DON, DAS, rapidly dividing cells,
4 dicoumerol: abortion, bleeding,
5 ergot: abortion, vasoconstriction, AGALAGTIA (no milk) impairs prolactin, and growth retardation in 3rd trimester.
