Instructor:Dr. Shahzad A. MuftiAdvisor Department of Biosciences

Teratogenesis: Genetic and Environmental causes

Genetic, Environmental, Thalidomide episode, DDT & bird egg cases. In 1964 Rubella cases.

Many teratogens in environment. Embryonic period (8-9 weeks) more susceptible, especially, 3 to 8 weeks.

Teratogenic Agents: Drugs & chemicals. Viruses, radiations, hyperthermia, maternal metabolic defects.

Teratogenesis

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Quinine, Alcohol, Heavy Nicotine and caffeine doses, smoking also reduces the number, quality and motility of sperms.

Pesticides. Many drugs e.g. valproic acid (anti-convulsant). Even “useful” substances such as retinoic acid------if in excess (13-cis-retinoic acid used for acne), especially thru its binding to neural crest cells)

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Alcohol another important teratogen. Fetal Alcohol Syndrome (FAS): small head, mental retardation, low IQ (68). Brain defects, fusion defects of upper lips.

Endocrine Disruptors: interfere with hormones, by binding with receptors or blocking synthesis of normal hormones.

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Examples: diethylstilbestrol, given (in 50’s and 60’s) to prevent miscarriage abnormal reproductive system in fetus.

HEAVY METALS: e.g. Zinc, Lead, Mercury etc used in industry, pollute soil, water, air….CNS defects.

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Pesticides: chlorinated hydrocarbons (DDT), Organophosphates, pyrethroids, Carbamates etc.

Other: over 50,000 artificial chemicals now used. Very little information available.

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FertilizationApril 20, 2023 7

DRUGS AND CHEMICALS IONIZING RADIATION (X-RAYS)Alcohol HYPERTHERMIAAminoglycosides (Gentamycin) INFECTION MICROORGANISMSAminopterin Coxsackie virusAntithyroid agents (PTU) CytomegalovirusBromine Herps simplexCigarette smoke ParvovirusCocaine Rubella (German measles)Cortisone Toxoplasma gondii (toxoplasmosis)Diethylstilbesterol (DES) Treponema Pallidum (syphilis)Diphenylhydantoin METABOLIC CONDITIONS IN THE MOTHERHeroin Autoimmune disease (including Rh incompatibility)Lead DiabetesMethylmercury Dietary deficiencies, malnutritionPenicillamine PhenylketonuriaRetinoic acid (Isotretinoin, Accutane)StreptomycinTetracyclineThalidomideTrimethadioneValproic acidWarfarinSource: Adapted from Opitz 1991. a This list includes known and possible teratogenic agents and is not exhaustive.

Some agents thought to cause disruptions in human fetal development