Reproductive toxicity

Question 1

What are the exogenous causes of malformations?

Answer 1

• Therapeutic drugs/environmental chemicals
• Radiation
• Maternal conditions
  (Infections, Maternal metabolism, Maternal allergic reaction, The woman’s general health (e.g. diabetes, rubella, alcohol abuse))

Question 2

When does embryonic development occur?

Answer 2

From fertilization to 7-8 weeks

Question 3

When does fetal development occur?

Answer 3

8-9 weeks until birth

Question 4

What is the developmental toxicology?

Answer 4

Alterations caused by chemicals to the development of the embryo, fetus or neonatal animal either morphological or functional

Question 5

What does teratogenesis concern?

Answer 5

Concerns the production of malformations.

Involves interference with the normal development of either embryo or fetus in utero resulting in abnormalities in the neonate.

Question 6

Which processes are involved in embryogenesis?

Answer 6

1) Cell proliferation
2) Cell differentiation
3) Cell migration
4) Organogenesis
5) Histogenesis - formation of tissue from undifferentiated cells
6) Functional maturation

Question 7

What predictions can be made on teratogenesis?

Answer 7

1) The sequence of events in embryogenesis could be easily disturbed, its interrelationships readily disrupted, and such interference could be very specific

2) The timing of the interference with the process of embryogenesis would be very important to the final expression of the teratogenic effect

Question 8

What is the toxic mechanism behind Thalidomide?

Answer 8

Mechanism:
Thalidomide-S has a high affinity to poly-G sequences in DNA
–> Inhibits the development of new blood vessels and micro-vessels
– > Inhibits the expression of integrins, transmembrane receptors, involved in cell adhesion during growth and differentiation
–> Binds specifically to genes involved in angiogenesis and integrin production

Question 9

How does Actinomycin D induce reproductive toxicity?

Answer 9

Actinomycin D interferes with transcription and thereby RNA synthesis –> Lead to cleft palate

Question 10

How does Folate acid (vitamin B9) induce reproductive toxicity?

Answer 10

Folate acid deficiency –> risk of spina bifida (a neural tube birth defect)
Spina bifida – When the vertebrae overlaying the spinal cord are not fully grown

Folate acid is used in bone growth during fetal development.

Question 11

How does Diphenylhydantoin induce reproductive toxicity?

Answer 11

An anticonvulsant drug used against epileptic.

Induce oral clefts.

Teratoxicity/malformations very much depend on the timing of administration!