DA3 - Principles of Teratology Flashcards
Teratology
Study of abnormal development
Teratogenesis
Study of abnormal mechanisms of development
Teratogen
Any agent that induces defects during development (radiation, infectious agents, drugs, environmental chemicals)
Congenital abnormality
any structural, functional, metabolic and behavioral disorder present at birth
Synonyms of congentical abnormality:
Anomaly, malformation, maldevelopment, birth defect
Disruptions vs. Deformations
Disruption: alteration of formed structures from destructive processes
Deformations: due to mechanical forces
Congenital abnormality facts:
- Caused by genetic or environment factors (usually a complex interaction of both)
- Incidence: poorly reported in domestic animals (vs. humans)
- Most are present at birth, others become obvious shortly after birth or later as the orgnaism matures
- May be structural or functional (absence of an organ vs. absence or defective enzymes)
- Show different degrees of severity
- May affect any body structure (internal and external)
- May occur as single or multiple conditions (syndrome)
- Some are species-specific or breed-specific (teratogens)
- some are gender specific
Syndrome
Multiple defects that have a specific common cause
Four maifestations of congenital anomalies
- Death
- Malformation
- Growth retardation
- Functional defect
Critical periods to abnormal development: Stage of development
Most critical determining factor
Critical periods to abnormal development: stage of pre-differentiation (Before organogenesis)
Effects
- Lethal - due to cytotoxic effect on embryonic cells
- None - embryonic cells are unresponsive
- The all or none rule
Critical periods to abnormal development: stage of differentiation
The stage of maximum susceptibility for structural abnormalities
- Effects - usually reflect upon a particular organ
Critical periods to abnormal development: stage of advanced morphogenesis
Susptibility declines as organogenesis advances
- effects: mostly functional (often hereditary)
- Some structures have more than one critical stage (palate)
- General rule: the earlier the insult, the more severe the consequences (eg. notochord –> CNS)
Causes of abnormal development: Embryo genotype
- Susceptibility to teratogens - depends upon ebryo genotype and its interaction with adverse environments (some teratogens have species-preference)
Causes of abnormal development: maternal conditions
- Genotype, nutrition, metabolic/organic diseases, exposure to toxic compounds
- Maternal supporting provisions can override zygote genotype
Abonrmal genes: mutations
- Occur by substitution, insertion, or deletion of bases
- Impact on animal - depends on the importance the the degree of alteration of final product
- Their incidence - increases with inbreeding because inbreeding reduces genetic variance and increases transmission of deleterious genes
Abnormal Chromosomes
Responsible for many defects and abortions
- Involve both, sex and somatic chromosomes
- Due to either abnormal number or abnormal structure
- Incidence in domestic animals - rare (or unreported?)
- Most are due to non-disjunction of chromosomes
- In most cases embryo is spontaneously aborted
- Phenotyping alterations - usually expressed as a syndrome
Klinefelter Syndrome
- Trisomy of sex chromosome - XXY karyotype
- Clinical features are seen only in males, detected at puberty: phenotypic male, gonadal dysgenesis, infertility
- Example: tortoise-shell (calico) male cat –> calico hair pattern is sex linked
- Is reported in all species
- Is the most common sex chromosome abnormality
Turner’s Syndrome
- Monosomy of sex chromosomes in female - XO karyotype
- Clinical features: phenotypic female, gonadal dysgenesis, infertility
- Reported in all species (most prevalent in pig, horse, cat)
- YO karyotype = lethal
Environmental Facotrs: Physical Factors
- Potent teratogens in all species
- Response: dose-dependent
- Avoid exposure of pregantn animals to radiation!!!
Environmental Facotrs: Chemical Factors
- Many therapeutic drugs: potential teratogens and carcinogens
- Effects depend on dosage and chemical structure
- Use cytotoxic drugs cautiously in pregnant animals!!!
Environmental Facotrs - Biological Factors
Biological Factors: Infectious agent
- Some cross placenta infecting embryo (some are lethal)
- Produce multiple defects especially in early developmental stages
- Investigate the effects of live-vaccines given to pregnant animals!
Environmental Factors - Plants
- Many plants contain toxic and teratogenic compounds
- Most commonly affected structure - appendicular skeleton
Description of altered morphogenic event denotes ….
the way in which defective development departs from normal
Classification: Developmental failure
- Agenesis or aplasia
- Causes: absence of primordial tissue or abnormal inductive tissue interaction
- Example: acardia (heart), amelia (limbs), kidney agenesis
Agenesis
Failure of development
Amelia
Congenital absence of limbs
Anencephaly
Congenital absence or reduction in size of cerebral hemispheres
Aplasia
Incomplete or defective development of a tissue or organ
Atresia
Congenital absence or closure of a normal body opening
Classification: Developmental excess
- In size (hyperplasia)
- In number
Classification: incomplete development
- Hypoplasia
- Cause: excessive vs. reduced cell proliferation
Classification: Failure to Fuse
- Cleft palate
- Septal heart defects
- Spina bifida
Classification: Failure of Migration
- Ectopia cordis
- Cryptorchidism
Classification: Persistence of embryonic structures (apoptosis and shaping of structures)
- Atresia: absence of natural body opening or lack of patency of a tubular structure (atresia ani, gut atresia)
Classification: duplication
Cojoined, paraiste twins
Classification: organ malpositioning
Dextrocardia, situs inversus
