10 – Teratology 2

Question 1

What is abnormal development influenced by?

Answer 1

1. Dose
2. Time
3. Duration of exposure
4. Species
   *functional changes with no more abnormalities=3rd trimester
   *if morphological damage=first trimester

Question 2

Male manifestations of abnormal development

Answer 2

1. Spermatogenesis
   a. Ex. ergot at high dose
2. Testis (not a big issue)
3. Secondary sex traits
   a. Ex. *mycotoxin (w/estrogenic properties)=infertility

Question 3

Female manifestations of abnormal development

Answer 3

1. Oogenesis/estrus
2. Early embryonic death
   a. Ex. lead
3. Failure to implant
   a. Ex. dairy cattle on high nitrogen diet (blood urea nitrogen is at high normal)
4. Abortion
   a. Long list: hypoxic, sweet clover poisoning (dicoumarol), lead, plants
5. Prolonged gestation
   a. Ex. iodine
6. Agalactia
   a. Ex. ergot
7. Malformation
   a. First trimester: 500!
8. Stillbirth
9. IUGR (inter-uterine growth retardation)
   a. 3rd trimester
10. Mummification of fetuses

Question 4

What are some causes of abnormal development?

Answer 4

• Genetic
• Infectious
• Nutritional deficiencies
• Poisonous plants
• Chemicals and drugs
• Mycotoxins

Question 5

Genetic causes of abnormal development

Answer 5

• Gene mutation
• 1. Autosomal (recessive, dominant, etc.)
• 2. Sex-linked (recessive gene)
• 3. Chromosomal abnormalities (not inheritable=self limiting)
• *manifestations could be anything!

Question 6

Chimera

Answer 6

• Mixture of DNA from 2 different sources (ex. freemartin twins)
  o Exchange of cells during pregnancy where this happens
• Ex. 2 different blood types

Question 7

Blue tongue virus

Answer 7

• Cattle and sheep
• Early exposure: embryonic death, resorption
• Later exposure: still birth, hydrocephalus, arthrogryposis

Question 8

Bovine viral diarrhea

Answer 8

• Cytopathic
  o Abortion
  o Early embryonic death
  o Placentitis
  o Infertility
  o Malformation cerebellar hypoplasia
  o Eye and jaw defects
• Non-cytopathic
  o Immunotolerance
• *persistent infection

Question 9

Parvovirus

Answer 9

• *effects rapidly dividing cells in pigs and dogs
• 1st trimester: resorption
• 2nd trimester: abortion/mummification
• 3rd trimester: few effects

Question 10

Feline Panleukopenia Virus

Answer 10

• Usually death
• Ataxia, oculovestibular problems due to cerebellar hypoplasia
  o *DDx: in this course=mercury
• Hydrocephalus

Question 11

Vitamin A deficiency

Answer 11

• Blind, micropthalmia
• Abortion, stillbirth
• CNS, renal and cardiac malformations

Question 12

Vitamin E/Se deficiency

Answer 12

• Cardiomyopathy
• White muscle disease in cattle

Question 13

Cooper (malindome)

Answer 13

• Enzootic ataxia in sheep
  o Anemic
  o Infertility

Question 14

Manganese deficiency

Answer 14

• Cartilage and limb development

Question 15

Iodine deficiency

Answer 15

• Prolonged gestation
• Goiter
• hairless

Question 16

Veratrum californicum (poisonous plant)

Answer 16

• SHEEP (species)
• agent: alkaloids cyclopamine, jervine
• *reduce neuroepithelial cell mitosis/migration
• *reduce chondrocyte proliferation

Question 17

Lupines (poisonous plants)

Answer 17

• *Crooked calf disease
• Arthrogryposis
• Cleft palate
• Spinal curvature (torticollis, scoliosis)
• Agent: alkaloid anagyrine

Question 18

Tobacco (nicotiana) (poisonous plant)

Answer 18

• Pigs: cleft palate, arthrogryposis
• Agent: anabasine

Question 19

**Vitamin A toxicity

Answer 19

• Mechanism: interferes with neural crest cell migration
• Fetal resorption
• **Microphthalmia
• Spina bifida
• Heart, GIT, urogenital defects
• *teratogenic at therapeutic dose
• **one of the most potent!

Question 20

Albendazole toxicity

Answer 20

• Anti-helminthic
• Mechanism: inhibits microtubule formation
• Spina bifida
• Bone, kidney defects

Question 21

Organophosphate insecticides toxicity

Answer 21

• Embryotoxic, fetotoxic
• CNS: learning impairment and behavioural change
• *Not as much developmental defects

Question 22

Organochlorin insecticides (DDT, lindane) toxicity

Answer 22

• Mechanism: estrogenic
• No implantation
• Resorption
• Reduced CL formation and reduced progesterone
• Reduced sperm
• *very difficult to purchase (more if it has been stored and exposed animals)

Question 23

Many other chemicals (fungicides, herbicides, antibiotics)

Answer 23

• Not particularly teratogenic with some exceptions

Question 24

Griseofulvin toxicity

Answer 24

• Not species specific
• Antifungal drug (ex. treat ringworm)
• Reduced microtubule and mitotic spindle function (mitotic interference)
• Abortion, resorption, bone, neural tube, cyclopia, anophthalmia (many systems but mainly CNS)

Question 25

Cyanide toxicity

Answer 25

• Plant origin
• Mechanism: effects energy and oxygen utilization
• **Arthrogryposis (limb development needs movement, and there is less movement due to lack of energy)
• *if too high=dead

Question 26

Nitrates toxicity

Answer 26

• Plant origin (ex. drought problem=can get high nitrates)
• Mechanism: *effects hemoglobin (oxidizes it) and get methemoglobin formation and anoxia
• Abortion
• *cows can adapt nitrate tolerance (fetus may not be able to adapt)

Question 27

Mycotoxins toxicity

Answer 27

• Fungal metabolites
• *increasing
• Potent=microgram/kg range (not just mg/kg range!)
  o Fetus is so susceptible
• Many effect rapidly dividing cells=ABORTION!
  o If having an abortion problem can ran a test panel (12 toxins)

Question 28

Zearalenone (mycotoxins toxicity)

Answer 28

• US problem with corn crops
• Estrogenic
• INFERTILITY
• *pigs more susceptible

Question 29

Aflatoxin (mycotoxins toxicity)

Answer 29

• Liver toxin
  o Can not metabolize drugs, chemicals or nutrients
• Rapidly dividing cells
• *also carcinogenic
• Extremely toxic!
• *NOT a problem in Canada unless importing fed

Question 30

Fumonisins (mycotoxins toxicity)

Answer 30

• ‘new’
• Rapidly dividing cells
• Other organ systems: lung, liver
• *horses and pigs
  o Horses: neurological component
• May cause abortion and resorption of fetuses

Question 31

Trichothecenes (mycotoxins toxicity)

Answer 31

• Many examples (will go over in a different lecture)
• Cytotoxic
• Affect rapidly dividing cells
• *abortion
• **#3 for occurrence in western Canada
• *swine

Question 32

Dicoumarol (mycotoxins toxicity)

Answer 32

• Abortion
• Bleeding
• *fetus is 3x more susceptible (mother may look normal)
  o Clotting time in mom, may be slightly increased
• *cattle most susceptible
• Horses are resistant=not very protein bond=leaves system quickly
• Sheep=even higher protein bound=doesn’t even reach the fetus
• Ex. in sweat clover bales (mold: coumarin to dicoumarol)
• (can get it from milk)

Question 33

Ergot (mycotoxins toxicity)

Answer 33

• *#1 problem in western Canada
• Abortion
• Vasoconstriction
• *dozen different alkaloids that cause the effects
• **species susceptibility
  o HORSES
  o Pigs and sheep (less)
  o Dairy (even less risk)
• *agalactiae and prolactin and stimulation of milk production (ex. sheep with NO milk)
  o Lamb mortality is high (can’t bottle feed everything)
• *growth retardation in 3rd trimester (not getting nutrients it needs, morphologically looks normal but just smaller)