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Types of Developmental Toxicants (Thalidomide (Purpose: Sleep aid AND as a…
Types of Developmental Toxicants
Thalidomide
Purpose: Sleep aid AND as a relief for nausea from pregnancy
Effects:
Absence of limbs, shortness of limbs, congenital heart defects, ocular malformations, renal malformations
Other:
Worldwide agencies developed assays to determine effects of compounds on development
Animal studies: "window" of teratogenic effects
Tobacco smoke
Effects:
Neuroteratogen from nicotine
Increase stress (chronic) in mother
Leads to spontaneous abortions, perinatal deaths, increased risk of Sudden Infant Death Syndrome (SIDS)
Learning and behavior problems (not associated with gross structural issues)
Other:
Leading cause of environmentally induced developmental disease and morbidity
25% women continue to smoke during pregnancy
Passive smoke is an issue
Purpose: Addiction, behavior, etc.
Diethylstilbestrol (DES)
Purpose: Stimulate estrogen and progesterone in placenta; help prevent miscarriage
Other:
Synthetic non-steroid estrogen
Effects:
Young women (daughters of mothers who were exposed to DES) are seen with clear cell adenocarcinoma
Linked to cancer
Increased risk of reproductive organ issues in males of mom with DES exposure
Ethanol
Effects:
Fetal Alcohol Syndrome (FAS) - craniofacial dysmorphism, intrauterine postnatal growth retardation, retarded psycomotor and intellectual development
Interference with Retinol metabolism/mechanisms in early pregnancy; potent stimulator developer
Other:
Alcoholic mother: FAS
Casual drinkers: Fetal Alcohol Spectrum Disorder
Purpose: drink and have a good time
Cocaine
Effects:
Premature labor, microcephaly, altered procephalic development, abnormal sleep, decreased birth weight, seizures, irritability, increased SIDS
Other:
Abuse led to epidemic health issue
Issues compounded by tobacco and alcohol use
Purpose: local anesthetic and vasoconstrictor
Retinoids (Vitamin A)
Effects:
Malformations in face, limbs, heart, CNS, skeleton
Cleft palate - activation of RXR receptors (nuclear receptors)
Link between elevated RA and schizophrenia
Other:
Signaling molecule - retinoic acid (RA) part of many developmental paths
Purpose: Dermatological preparations (help clear the skin)
Valporic Acid
Effects:
Spina bifida
Other:
All antiepileptic drugs have teratogenic effects
Purpose: anticonvulsant first marketed in Europe
Used by epileptics to control seizures
Angiotensin System
Effects:
Angiotensin II binds to AT1 receptors - vasoconstrictor
Inhibitors - lower blood pressure
Second-trimester effects:
Fetal growth retardation, pulmonary hypoplasia, joint issues, hypocalvaria, neonatal renal failure, death
Other:
ACE inhibitors (Angiotensin Converting Enzyme)
Maybe causes reduced amnioitic flud
Purpose: Blood pressure control