Lecture 4 - Teratogens

Lack in Nutrition

• Nutrition is key (good amount of food, protein, vitamins, minerals)

• Inadequate nutrition can rsult in premature birth and low birth weight.

• Low folic acid can cause risk of spina bifina (spinal protrusions).

3 Other general risk factors for birth defects

• Stress can decrease oxygen supply to the fetus amd weakens the immune system of the mother, also leading to alcohol and drug consumption.

  • Leads to low birth weight and premature birth.

• Old age of mother (miscarriages/stillbirth)

• Teratogens will reduce intelligence levels and are always and only a population effect.

Critical Periods of Development

• Critical periods have intense development and rapid cell division.

• During this period, organs are vulnerable to toxins, viruses and genetic abnormalities.

• If normal development is altered, birth defects or defects later are more probable.

Effect determinants of teratogens

• Organism, genetic susceptibility, timing (zygote, embryonic, fetal period), dose, heredity, and age of parental organism, poor nutrituion, lack of prenatal care, psycological state and multiple teratogents may worsen the impact of one teratogen

Effects of Alcohol

• Induced during prenatal life, but mostly refer to postnatal exposure (effects later in life).

• Toxic effects include: Shrinking cerebellum, Increased ventricular size, Pancreas inflammation

Pharmacological Teratogens

Thalidomide, Aspirin, Antibiotics, Diethylstilbesterol, Bisphenol A, Retinoic Acid (Accutane)

Recreational Teratogens (drugs of abuse)

Alcohol

Tobacco & nicotine

Cocaine, heroin, methadone

Infectious Agents

Toxoplasma gondii

Rubella

Zika

CMV

Herpes

Syphilis

SARS-CoV2

Environmental Hazards

Radiation, Pesticides/herbicides

2,3,7,8-T  (tetrachlorodibenzo-p-dioxin)

Environmental Pollutants, Lead, Mercury, Radioactivity

Microplastics

Thalidomide

• Drug given to mothers to prevent morning sickness during first trimester.

• Critical period for limb formation.

• Babies born without long bones of their arms and legs.

• Drug still used today

Asprin

• In large quantities, causes miscarraiges, bleeding and newborn respiratory problem.

  • Yet seems to protect from low birth weight.

  • Low does can reduce risks of preeclampsia (high bp) in women of risk.

Antibiotics

• streptomycin, kanamycin (aminoglycoside antibiotics) and tetracycline lead to:

• Fetal effects:

  • hearing loss

  • weakening, hypoplasia, and discoloration of teeth & growth impairment of long bones, hepatotoxicity (liver damage) during pregnancy.

• Maternal Effects

  • can reduce the effectiveness of contraceptive pills

Bisphenol A: endocrine disrupting chemical

• BPA = endocrine disruptor

• Has estrogen-like effects (In the brain it mimics or blocks normal effects of estrogens)

• Can leach from plastics

• Associated with developmental and reproductive toxicity

• Estrogens are necessary for normal brain development, and maintenance of synaptic plasticity

Rubella

• If 1st trimester mother gets it 20% embryo also gets it.

• Results: congenital rubella syndrome, cardiac effects, deafness, mental retardation, eye anomalies, spontaneous abortions, still-borm babies.

Zika

• Bite from infected mosquito.

• Unsafe sex with infected person.

• If infection occurs during pregnancy → can cause Congenital Zika Syndrome.

• Main effects:

  • Severe microcephaly (small head, brain underdeveloped)

  • Brain damage and reduced brain tissue

  • Eye damage → vision problems

  • Joint abnormalities (e.g., clubfoot)

  • Increased muscle tone (stiff body)

  • Seizures

  • Feeding, hearing, and developmental problems

• Uncertainties:

  • Exact risk of birth defects after infection

  • Full long-term effects into adulthood

Radiation

High doses of radiation at work places lead to chromosomal abnormalities; prenatal death; mental retardation

Environmental pollutants

• Environmental pollutants and toxic wastes: such as mercury, lead and microplastics

  • prenatal exposure to lead affects children’s mental development

  • mercury poisoning (minimata disease): disorders of the CNS, small heads

  • Vietnam: Agent orange or dioxin spraying

Drugs of Abuse

Tobbaco

Marijuana

Cocaine

Heroine

Tobacco

fetal and neonatal deaths; preterm births and lower birth weights; sudden infant death syndrome (SIDS); poorer language and cognitive development at 4 years

Marijuana

Growth retardation; premature birth; poorer verbal and memory development at 4 years of age

Cocaine & Crack

Growth retardation; spontaneous abortion; premature birth; withdrawal symptoms such as tremors and irritability

Heroin and methadone

Deficient growth; SIDS; withdrawal symptoms; premature birth.

Nicotine in Fetus

• Nicotine constricts blood vessels

  • Reduces blood flow to the uterus and causes placenta to grow abnormally

    • Reduces the transfer of nutrients to the fetus

• Nicotine raises the concentration of carbon monoxide (and decreases oxygen) in mother’s and fetus’ bloodstreams

  • Likely to slow fetal growth and may damage CNS

Normal Prenatal Brain

• Dorsal ectoderm thickens → forms neural tube

• Neural tube surrounds a fluid-filled cavity

• Anterior (front) part enlarges → forms:

  • Forebrain

  • Midbrain

  • Hindbrain

• Remaining neural tube → becomes spinal cord

Nicotine Exposed Prenatal Brain

10 µM nicotine for 48 hours:

• ↑ Cell death (pyknotic cells)

• ↓ Cell division (mitosis)

• Cell death > reduction in mitosis

Alcohol Related Birth Defects

• Fetal Alcohol Syndrome (FAS) characteritics by CNS issues, low birth weight and height and atypical facial features.

• Fetal Alcohol Effects (FAE) results from alcohol abuse are found in absence of full-blown syndrome.

FAS facial features

smaller head, small eyelid opening, short upturned nose, Long upper lip with a thin red border and a deficient central groove, undeveloped outer ear.

FAS behavioural features

attention deficits, language issues, learning disabilitiies, impulsive behaviour, poor judgement.

Brain shape changes through Alcohol

• Midline structures of brain are deficient in alcohol-exposed mouse embryos.

• The brain of an alcohol-exposed mouse has defects in midline structures;

• This correlates to defective midline structures seen in FAS children

• Alcohol disrupts midlines in all species.