EDCs + Teratogens

definitions and examples of EDCs and Teratogens to hammer out the differences and similarities :)

EDC examples

Phthalates
DES
DDT
Atrazine
BPA

EDCs overall

interfere with the endocrine system, mimicking, blocking, or altering hormonal signals

• testicular dysgenesis, abnormal anogenital distance, and impaired fertility by disrupting androgen and estrogen pathways

• primarily reproductive effects

Teratogen examples

Thalidomide

Mercury

Alcohol

Retinoic Acid

Teratogen overall

substances that cause structural malformations or functional deficits in the developing embryo or fetus

• specific critical windows of development, such as organogenesis or the development of the central nervous system (CNS)

• primarily neurodevelopmental effects

Phthalates

EDC

• flexible plastics

• reproductive effects

• testicular dysgenesis syndrome

  • cryptorchidism

  • hypospadias

• active metabolites act as anti-androgens, disrupting testosterone synthesis by inhibiting enzymes in Leydig cells

• a specific ______ syndrome - reduced anogenital distance

• though EDC, has teratogenic effects

Cryptorchidism

one/both testicles fail to move into the scrotum prior to birth

Hypospadias

opening of the urethra is on the underside rather than at the end of the penis

• common abnormality

DES

EDC

• most potent xenoestrogens, higher binding affinity

• given to manage morning sickness

• inhibits Hoxa10 (homeobox-a10) expression involved in Wnt7a signalling

• participates in developmental patterning of male and female reproductive systems under the regulation of estrogens

• women: implantation failure, increased embryo resorptions

• males: infertility and cryptorchidism

BPA

EDC

• plastic products

• weak estrogen binders

• epigenetic modifications interact with estrogen receptors inducing mammary, ovary, uterus epithelial cell proliferation

• involved with agouti gene

• ovulatory effects

• infertility

• lots of exposure to vulnerable populations

DDT

EDC

• pesticide

• travels long distances in atmosphere

• thinning of bird eggshells

• liver and kidney damage

• neurotoxin effects

• teratogenic effects

• carcinogenic effects (breast cancer in women)

Atrazine

EDC

• pesticide found in groundwater

• inexpensive and cost effective

• caused feminization in male frogs

• human effects: abortion, growth delay, GD, PTB, congenital deformities

Thalidomide

Teratogen

• used to treat morning sickness in pregnant women

• internal organ damage (brain, eyes, hearing)

• interferes with limb budding development

• acts primarily by blocking angiogenesis = small limbs, or phocomelia

• complex molecule

  • byproducts are teratogenic metabolites (anti-angiogenic in blood vessels that are necessary for growth and development)

• S enantiomer inhibits release of TNF-alpha

Mercury

Teratogen

• neurological embryonic abnormalities

• primary action: protein and enzyme inhibition in neurological processes by binding to sulfhydryl or thiol groups (increased affinity for sulphur)

• readily crosses placenta and blood brain barrier

• can produce deficits in attention, behaviour, cognition, and motor skills in children

Alcohol

Teratogen

• damage to hippocampus

• intellectual and neurodevelopmental defects

• behavioural abnormalities

• mechanisms:

  • altered neurogenesis (migration of neural crest cells - prematurely initiate differentiation into facial bones = NTDs)

  • oxidative stress

    • cell death caused by formation of superoxide free radicals- oxidative damage to cells

  • epigenetic modifications

    • alter DNA methylation and histone deacetylation which regulate gene expression during brain development = cognitive def.

• impact serotonin and GABA

• FAS

factors affecting whether alcohol will have an effect on developing fetus

1. dose and frequency of exposure - during the first trimester, alcohol will impact organogenesis and structural defects, during the third trimester, alcohol will impact cognitive and behavioral issues - both contribute to FAS

2. maternal genotype - variations in genes encoding enzymes like ADH and ALDH determines how quickly the mother will be able to metabolize alcohol

3. fetal genotype - genetic susceptibility and variation in metabolism and neurodevelopment will influence how the fetus will react to alcohol exposure

retinoic acid

Teratogen

• formation of the anterior-posterior axis (necessary for development but too much = reactions in normal cells)

• formation of heart and jaw

• NTDs, nervous system, skull, face, eyes, limbs

• mechanisms (3)

  • alters gene expression of HOX genes responsible in anterior-posterior axis, and neural crest cells

  • binds to and and inhibits migration of neural crest cells

  • activates RA degrading enzymes causing deficiencies

• glyphosate

  • upregulates RA activity and suppresses SHH pathway (resp for dorsal midline, without it = brain, spinal cord and limbs defects)

tobacco smoke

Teratogen

• retards growth and increases fetal death

• nicotine - damage fetal brain and lungs during development (increases lung problems later on)

• carbon monoxide - restrict oxygen to developing fetus

marijuana

Teratogen

• may have subtle teratogenic effects in altering brain development

• cannabinols

  • impair testes function

  • subtle effects in brain function

• cannabinoids

  • altered migration of neuroblasts in rats’ cerebral cortex and cognitive and memory decline

    • GPCRs found in brain involved in emotional, behavioural reactions, homeostasis, learning, etc.

• THC

  • alters EC system and interferes with natural cannabinoid activity

  • changes in hippocampus, memory, addiction, and mental health

ACE inhibitors

Teratogen

• fetal toxicity

• renal insufficiency

• hyperkalemia

• FGR

• fetal death

• lower BP in maternal lungs and fetus

• (other: lower BP in maternal lungs and fetus,

• lung hypoplasia, prematurity)

Warfarin

Teratogen

• rat poison

• increased miscarriages

• blood thinning drug

• nervous system defects

• mental retardation

• optic nerves

• hearing

Valproic acid

Teratogen

• causes histone hyperacetylation by inhibiting histone deacetylation

• autism-like development problems due to effects on histone deacetylation

• blocks folate = NTDs

herpes-simplex

Teratogen

• potentially fatal condition for fetus

• causes blindness, deafness, CP, mental def. in later exposure

• fatal in early exposure

CMV

Teratogen

• common virus

• hearing loss at birth and sometimes blindness

• rare to get symptoms initially unless bad immune system

• reactivation in women who had previous infection, likely congenital

toxoplasmosis

Teratogen

• cat feces

• only risk for unborn baby if first contracted during pregnancy or early before pregnancy

• can cause miscarriage, stillbirth, damage to brain and eyes

• blindness in childhood