Summary: Reproductive Toxicology

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• What is the definition of developmental or reproductive toxicology?

  It encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis and outcomes potentially leading to adverse health effects.  So it includes malformations, growth retardation, functional or metabolic impairment and/or death of the organism.

• In what kind of defects can a teratogen result?

  Defects in:
  - differentiation
  - growth
  - function
  - malformation
  - death foetus/embryo

• What are adverse outcomes of pregnancies and how often do they occur?

  - pregnancy loss (spontaneous abortions): 60-70%
  - major birth defects: 2-3% (structural changes that are already present at birth)
  - minor birth defects: 14%
  - low birth weight 7%
  - infant mortality 1.4%
  - abnormal neurological functions 16-17%
  Completely normal, healthy: 60%

• What are the causes of birth defects?

  - teratogen induced: 1-3%
  - virus infection and diseases mother 7%
  - chromosomal aberrations: 3-5%
  - unknown factors inc. food deficiency: 65-70%
  - genetic factors: 15-25%

• What are examples of teratogenic compounds?

  1) Softenon
  2) Diethylstilboestrol (DES)
  3) Retinoids
  4) Valproic acid
  
  5) anti-epileptics
  6) ACE-inhibitors
  7) COX-inhibitors
  8) Cocaine
  
  9) Alcohol
  10) Irradiation
  11) Dietary deficiencies, folic acid
  12) Tabacco smoke
  
  and 20 more other drugs.

• What are probably the teratogenic mechanisms behind thalidomide?

  - effects on angiogenesis
  - integrin regulation
  - oxidative DNA damage
  - TNF alfa inhibition
  - growth factor antagonism
  - effects on glutathione and redox status
  - inhibition of ubiquitin-mediated protein degradation

• What are consequences of smoking during pregnancy?

  - Sudden infant death sydrome (SIDS)
  - spontaneous abortions
  - perinatal deaths
  - learning, behavior and attention disorders
  - lower birth weight

• What are consequences of cocaine use during pregnancy?

  It is different to meassure the effects of cocaine because very often cocaine is taken together with for example alcohol or smoking. But registered effects are abruptio placentae, preterm birth, low birth weight.

• What can be concequences of retinoids use during pregnancy?

  Retinoids (like vitamin A; retinol) can induce malformations on the face, limbs, heart, CNS and skeleton. The RXR-alfpha receptor turned out to play a big role in those processes.

• What can be a consequence of the use of AED during pregnancy?

  Especially the usage of first generation AEDs like Valproic acid, phenytoin,  carbamazepine can induce malformations like: craniofacial abnormalities, limb defects, growth deficiency, mild to moderate metal retardation. Especially with valproic acid spina bifida is reported very often. Therefore it is adviced for pregnant women to use folic supplements during gestational period.