THE ENVIRONMENT

AND THE DEVELOPING

EMBRYOMrs. Ofelia Solano Saludar

Department of Natural SciencesUniversity of St. La Salle

The ENVIRONMENT is an integral factor in development All stages of embryonic and fetal

development are vulnerable to environmental changes.

Disturbances may result to miscarriages or they may express grotesque teratogenicity.

They may change gene expression that may be carried into the next generation (transgeneration effects: epigenomes).

TERATOGENS are environmental agents that cause developmental defects in the fetus.

They are non-genetic factors that interfere with normal embryonic and fetal differentiation and morphogenesis.

Children who have been exposed to teratogens in utero will not pass their defect on to their children.

TERATOGENIC EFFECTS

In Our Stolen Future, Theo Colburn, Dianne Dumanoski, and John P. Myers (Dutton, NY, 1996), put forth the evidence that numerous chemicals used as pesticides, herbicides, and plasticisers interacted with the endocrine systems of adult and developing animals (including humans).

These are neurotoxins/endocrine disruptors.External factorsHeavy metalsPesticidesPlastics

3 polyvinyl6 polystyrene7 polycarbonate

Internal factors1. Embryonic endogenous2. Maternal health

Nutrition Microbes Alcohol Recreation Marijuana drugs Nicotine Medication

Transplacental transmission of pollutants: Placenta does NOT adequately protect the fetus. The fetus is NOT adequately protected by the

blood barrier system.

STAGES OF SUSCEPTIBILITY OF EMBRYO TO TERATOGENICITY

Before 1961, there was very little evidence for drug-induced malformations in humans.

Lenz and McBride independently accumulated evidence that a mild sedative, thalidomide, caused an enormous increase in a previously rare syndrome of congenital anomalies.

Over 8000 affected infants were born to women who had taken this drug

One tablet taken can produce a child with all four limbs deformed .

Other abnormalities induced by the ingestion of thalidomide included heart defects, absence of the external ears, and malformed intestines.

The drug was withdrawn from the market in November, 1961.

PHOCOMELIA: Knockout of HOX genes

THALIDOMIDE SYNDROME

Researches show that there are more incidence of conjoined twins in Asia than in America and Europe.

High incidence in India, Pakistan than in any Asian country

High incidence among the lower income families.

Indian girl with EIGHT LIMBS; Indian baby with TWO FACES

LIMB DEVELOPMENT

AER: Apical ectodermal ridge

Removal of AER stops limb development

Addition of AER causes formation of 2nd limb

Splitting AER leads to 2nd limb

• Methylmercury injury of the nervous system

• Preferential sites in the nervous system

• The lesions show characteristic signs and symptoms in Minamata disease.

MINAMATA DISEASE

DEPLETED URANIUM: A Silent but Deadly Enemy

Depleted uranium is roughly 60% as radioactive as naturally occurring uranium, and has a half life of 4.5 billion years.

800 tons of DU is the atomic equivalent of 83,000 Nagasaki bombs. 

The U.S. has used more DU since 1991 than the atomicity equivalent of 400,000 Nagasaki bombs. 

Four nuclear wars and atmospheric testing release10 times the amount of radiation into the atmosphere!

Effect of DU on biological systems: particulate effect from nano-size particles occurs immediately after exposure and targets DNA

DU Poisining in Iraqi Children: The horrors of war are “felt” in the womb!

SYPHILIS

Untreated maternal syphilis results in fetal infection 75-90% of the time.

Early infection most often results in spontaneous abortion.

Some newborns do survive but are small for gestational age, anemic with spleen and liver malformations, have skin lesions and nasal discharge and bone and joint pain.

Gestationally late infections often present in children over 2 years of age. They have nerve deafness, dental and bony abnormalities, cardiovascular defects and skin lesions.

CONGENITAL SYPHILIS

Retinoic acid is the active ingredient in DERMAL CREAM

Exposed children may develop hydrocephaly, ear malformations, cardiovascular defects and decreased IQ

RETINOIC ACID SYNDROME

FETAL ALCOHOL

SYNDROME

Humans are most susceptible to alcohol-related neurological

damage during a period when the brain cells are developing quickly (6th

month of gestation until 2 years after birth)

Polystyrene is made into styrofoam food packaging, audiocassette housings, CD cases, disposable cutlery.

Polystyrene production process generates the 5th largest amount of toxic waste of any single chemical production process.

Styrene monomer leaches in hot and cold water, and form a 50% ethanol-water mixture.

The “McToxics Campaign,” arose when many environmental health protection agencies pushed McDonald’s to abandon its use of the Styrofoam that packaged every hamburger it sold nationwide.

In the Philippines, many food establishments STILL continue using styrofoam packaging.

POLYSTYRENE

POLYCARBONATE• Polycarbonate is among the plastics

classified as code 7. • Polycarbonate is found in baby bottles,

food packaging, reusable water bottles, coffeemakers, dental sealants.

• One component of polycarbonate is Bisphenol A.

• This chemical leaches out of polycarbonate plastic when it is heated, exposed to acids or with simple wear and tear.

• Avoid using with food the plastics with recycle codes 3,6 and 7.

17ß-estradiol is a potent estrogen synthesized in the ovary, placenta, testis and adrenal cortex. BPA is about 10,000-fold less potent than this.

When BPA is combined with other xenoestrogens (estrogens from outside the body), they act in synergism, effectively raising the body load of estrogen to dangerous levels

The fetus is most vulnerable to the effects of the chemical during the perinatal period, which begins with completion of the 20th to 28th week of gestation and ends 7 to 28 days after birth.

Exposure to BPA increases risk of mammary tumors

BPA is a XENOESTROGEN

makers of Nestlé, Similac, Enfamil and PBM said that they use BPA in the linings of metal cans holding liquid

formula.

BPA in cola cans prolong

shelf life

The famous Nalgene

bottle has BPA

BPA in baby bottles

NEW!!! BPA-free

• Polyvinyl chloride (PVC) is the most widely used form of PLASTIC.

• Found in a wide variety of products: food packaging, children’s toys (including the most expensive Barbie dolls), teethers, plumbing and building materials, medical devices.

• VINYL CHLORIDE, the chemical used to make PVC, have been linked to cancer and kidney damage

• They are also known to have serious effects on reproduction, and could be responsible for the symptoms of the PHTHALATE SYNDROME: low testosterone in fetal males, hypospadias, inhibition of normal scrotal development, undescended testes, and testicular tumors.

POLYVINYL CHLORIDE

INTERSEXES

HYPOSPADIA: 5-alpha reductase deficiency

• Absence of Mullerian Inhibiting hormone (MIH) results to the nonregression of the derivatives of the Mullerian duct (fallopian tube, uterus, part of vagina)• The presence of these

remnants results to the failure of testes to descend into the scrotum

CRYPTORCHID

TERATOGENS: WHAT TO AVOID DURING PREGNANCY Varicella Virus (chickenpox)- skin scarring, a

small head, blindness, seizures, low birth weight, and mental retardation.

Tobacco- placenta may not develop normally causing placenta previa; fetus has increased risk of developing heart defects and being born at a low birthrate, increased risk of SIDS, asthma, and other lung related problems.

Alcohol- fetal alcohol syndrome (FAS) causes mental retardation and birth defects: abnormal facial features, growth deficiencies

Accutane- controls and prevents acne. Exposed fetus likely to develop either facial deformities, heart defects, a small head, cleft lip and palate, a buildup of fluid in the brain, or mental retardation. 

TERATOGENS: WHAT TO AVOID DURING PREGNANCY

HIV- congenital HIV DES (diethylstilbesterol)- used to

prevent miscarriages; risk for developing reproductive tract cancer; male fetus is at risk of developing abnormal genitalia 

Thalidomide- control nausea during pregnancy.  Cause defective intestines and anomalies with eyes and vision, severe limb malformations

Radiation - reduction in height, severe mental retardation, small head size, impaired brain development, childhood leukemia, and cancer in later life.

Lead- spontaneous abortion, low birth weight, premature birth, and developing abnormal skin markings, undescended testicles in male babies.

Rubella- vision and hearing problems, heart abnormalities, mental retardation

Syphilis- cause stillbirth or death shortly after birth. 

Toxoplasmosis- parasitic infection.  Fetus has increased risk for mental retardation, pneumonia, eye infections, jaundice, and hydrocephalus.  A surviving baby may be prone to seizures and to developing cerebral palsy.

TERATOGENS: WHAT TO AVOID DURING PREGNANCY

Cytomegalovirus (CMV)- herpes virus. Cause hearing loss, mental retardation, vision loss, liver/lung/spleen problems and dental anomalies.

Phenytoin (or Dilantin)- treatment for seizures. Fetus has increased risk for developing a cleft palate, heart defects, small heads, abnormalities in the fingers and nails, and some mild developmental disabilities. 

Mercury- introduce a variety of unpredictable mutations in the developing fetus, especially to their nervous system. 

Arsenic- increased risk of spontaneous abortion, low birth rate, and even stillbirth.

TERATOGENS: WHAT TO AVOID DURING PREGNANCY